Helical nerve cuff and related implantable device

Abstract

[0003] Described herein are helical nerve cuffs and implantable devices comprising a body comprising a helical nerve cuff and a wireless communication system. The implantable device may include: a body having a wireless communication system, an electrode capable of detecting electrophysiological signals transmitted by a nerve or emitting electrical pulses to a nerve, and a helical nerve cuff. Also described are methods of implanting the helical nerve cuffs and implantable devices, as well as methods of making the helical nerve cuffs and implantable devices.

Description

Technical Field

[0001] [Cross - Reference to Related Applications] This application claims the benefit of priority to U.S. Provisional Application No. 62 / 916,709, filed October 17, 2019, which is incorporated herein by reference for all purposes.

[0002] [Technical Field] A helical nerve cuff and an implantable device comprising the helical nerve cuff and a wireless communication system are described herein. Also described are methods of implanting the helical nerve cuff and the implantable device, and methods of fabricating the helical nerve cuff and the implantable device.

Background Art

[0003] The peripheral nervous system of an individual functions to tightly control the activities of organs necessary for life support and physiological homeostasis. Electrical pulses (i.e., action potentials) transmitted via nerves can alter various physiological functions such as heart rate, inflammation, and bladder or bowel control. Certain medical conditions can occur when these nerve signals fail to properly control the body by either over - stimulating or under - stimulating target organs.

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

[0005] Nerve cuffs developed to date have been larger or not easily accessible to peripheral nerves. However, such nerve cuffs may not be suitable for a particular nerve or may not be easily implantable. SUMMARY OF THE INVENTION

[0006] An implantable device comprising a helical nerve cuff and a body comprising a wireless communication system with the helical nerve cuff is described herein. The body can be attached to the outer surface of the helical nerve cuff. Also described are methods of implanting the helical nerve cuff and the implantable device, as well as methods of fabricating the helical nerve cuff and the implantable device.

[0007] An implantable device may comprise a body including a wireless communication system, two or more electrodes configured to electrically communicate with a wireless communication system configured to detect electrophysiological signals transmitted by nerves or emit electrical pulses to nerves, and a helical nerve cuff comprising at least one of the two or more electrodes, wherein the body is on the helical nerve cuff, the helical nerve cuff at least partially wraps around fibrous tissue having a nerve, and at least one of the two or more electrodes is disposed to electrically communicate with the nerve.

[0008] In some embodiments, the wireless communication system comprises an ultrasonic transducer. In some embodiments, the ultrasonic transducer has a length of about 5 mm or less in its longest dimension. In some embodiments, the wireless communication system comprises two or more ultrasonic transducers.

[0009] In some embodiments, the wireless communication system comprises a radio frequency antenna.

[0010] In some embodiments, the wireless communication system is configured to receive ultrasonic or radio frequency and convert the energy from the ultrasonic or radio frequency into electrical energy to power the device.

[0011] In some embodiments, the helical nerve cuff is configured to wrap around the nerve at least once. In some embodiments, the helical nerve cuff is configured to wrap around the nerve about 1.3 to about 1.7 turns.

[0012] In some embodiments, the helical nerve cuff has a width defining an inner surface, a first edge, and a second edge of the helical nerve cuff, and when the helical nerve cuff is in a relaxed position, at least a portion of the first edge contacts at least a portion of the second edge.

[0013] In some embodiments, the helical nerve cuff has a width that defines an inner surface, a first edge, and a second edge of the helical nerve cuff, and when the helical nerve cuff is in a relaxed position, the first edge does not contact the second edge.

[0014] In some embodiments, at least one of the two or more electrodes is disposed along the length of the helical nerve cuff. In some embodiments, at least one of the two or more electrodes disposed along the length of the helical nerve cuff is disposed on the inner surface of the helical nerve cuff.

[0015] At least one of the electrodes of the helical nerve cuff can include one or more serpentine segments.

[0016] In some embodiments, the helical nerve cuff is flexible and configurable to a bent position by (a) at least partially rewinding the helical nerve cuff and (b) to a relaxed position.

[0017] In some embodiments, the implantable device further comprises a helical nerve cuff or one or more handle portions attached to the body. In some embodiments, the handle portion includes a loop. In some embodiments, the handle portion includes a filament. In some embodiments, the handle portion is attached to the nerve cuff at a position proximal to an end of the helical nerve cuff. In some embodiments, the implantable device further comprises a second handle portion attached to the helical nerve cuff at a position proximal to a second end of the helical nerve cuff. In some embodiments, the first handle portion is attached to the second handle. In some embodiments, the device further comprises an additional handle portion attached at an intermediate position along the length of the helical nerve cuff.

[0018] An implantable device can include a mount configured to receive a body and a helical nerve cuff, thereby attaching the body to the helical nerve cuff. Alternatively, the body can be attached directly to the helical nerve cuff, such as to an outer surface of the helical nerve cuff, or the body can be attached to an end of the helical nerve cuff. In some embodiments, the body is attached to an intermediate portion of the helical nerve cuff. In some embodiments, the body includes an attachment end attached to the helical nerve cuff and an extension end extending from the attachment end.

[0019] In some embodiments, the helical nerve cuff includes a right-handed helix portion. In some embodiments, the helical nerve cuff includes a left-handed helix portion. In some embodiments, the helical nerve cuff includes a right-handed helix portion joined to a left-handed helix portion. In some embodiments, the body is attached to the helical nerve cuff at a proximal location where the right-handed helix portion is joined to the left-handed helix portion. In some embodiments, the right-handed helix portion is joined to the left-handed helix portion via a straight joining portion.

[0020] In some embodiments, the helical nerve cuff includes one or more electrodes configured to emit electrical pulses to a nerve. In some embodiments, the helical nerve cuff includes one or more electrodes configured to detect electrophysiological signals transmitted by a nerve. In some embodiments, the helical nerve cuff includes two or more electrodes configured to detect electrophysiological signals transmitted by a nerve.

[0021] In some embodiments, the nerve is a human splenic nerve. In some embodiments, the nerve is a human visceral nerve.

[0022] In some embodiments, the body includes a housing. In some embodiments, the housing is configured as one of two or more electrodes. In some embodiments, the housing includes an acoustic window. In some embodiments, the housing includes an acoustically conductive material.

[0023] In some embodiments, the body includes an integrated circuit electrically connected to a wireless communication system and two or more electrodes. In some embodiments, the integrated circuit includes an energy storage circuit including a capacitor.

[0024] In some embodiments, the body has a length of about 8 mm or less in its longest dimension.

[0025] In one embodiment, the wireless communication system is configured to transmit data. In some embodiments, the wireless communication system is configured to emit ultrasonic backscatter or radio frequency backscatter that encodes data. In some embodiments, the data includes information related to an electrophysiological signal that has been detected, a measured physiological state, a device state, or an emitted electrical pulse.

[0026] In some embodiments, the wireless communication system is configured to receive instructions for operating an implantable device. In some embodiments, the instructions are encoded by ultrasound or radio frequency. In some embodiments, the support includes a trigger signal that operates the implantable device to emit an electrical pulse to a nerve.

[0027] In some embodiments, the implantable device further includes a sensor configured to detect a physiological state. In some embodiments, the sensor is configured to detect temperature, pH, pressure, strain, or analyte concentration.

[0028] In some embodiments, the fibrous tissue includes blood vessels.

[0029] Also, this specification describes a system comprising any one of the above-described implantable devices, and an interrogator comprising a second wireless communication system configured to wirelessly communicate with the wireless communication system of the implantable device. In some embodiments, the second wireless communication system comprises one or more ultrasonic transducers configured to transmit ultrasonic waves to the implantable medical device, and the ultrasonic waves supply power to the implantable medical device. In some embodiments, the second wireless communication system comprises one or more radio frequency antennas configured to transmit radio frequencies to the implantable medical device, and the radio frequencies supply power to the implantable medical device. In some embodiments, the interrogator is configured to be worn externally.

[0030] Furthermore, this specification describes a nerve cuff comprising a flexible helical substrate configured to at least partially wrap around fibrous tissue including a nerve, the flexible helical substrate being configurable between (a) a bent position by at least partially rewinding the helical nerve cuff and (b) a relaxed position, one or more electrodes disposed along the length of the helical substrate, and a handle portion attached to the helical substrate and configured to apply a force that forms the helical substrate in the bent position.

[0031] In some embodiments of the helical nerve cuff, the handle portion includes a loop. In some embodiments, the handle portion includes a filament. In some embodiments, a portion of the handle portion is embedded within the substrate. In some embodiments, the handle portion is attached to the nerve cuff at a position proximal to the end of the helical nerve cuff. In some embodiments, the helical nerve cuff includes a second handle portion attached to the helical nerve cuff at a position proximal to the second end of the helical nerve cuff. In some embodiments, the first handle portion and the second handle portion are separated by a radial angle of about 90° to about 180° around the helical axis. In some embodiments, the first handle portion is attached to the second handle portion. In some embodiments, the helical nerve cuff includes an additional handle portion attached at an intermediate position along the length of the helical nerve cuff.

[0032] One or more electrodes of the helical nerve cuff may include one or more serpentine segments.

[0033] In some embodiments, the helical nerve cuff is configured to wrap around the nerve at least once. In some embodiments, the helical nerve cuff is configured to wrap around the nerve about 1.3 to about 1.7 times.

[0034] In some embodiments, the substrate of the helical nerve cuff has a width that defines an inner surface, a first edge of the substrate, and a second edge of the substrate, and when the nerve cuff is in the relaxed position, at least a portion of the first edge contacts at least a portion of the second edge.

[0035] In some embodiments, the substrate of the helical nerve cuff has a width that defines an inner surface, a first edge of the substrate, and a second edge of the substrate, and when the nerve cuff is in the relaxed position, the first edge does not contact the second edge.

[0036] In some embodiments, at least one of the one or more electrodes of the helical nerve cuff is disposed along the length of the helical nerve cuff. In some embodiments, at least one of the one or more electrodes disposed along the length of the helical nerve cuff is disposed on the inner surface of the helical nerve cuff.

[0037] In some embodiments, the helical nerve cuff is configured to be wound back at least one turn.

[0038] In some embodiments, the helical nerve cuff includes a right-handed helical portion. In some embodiments, the helical nerve cuff includes a left-handed helical portion. In some embodiments, the helical nerve cuff includes a right-handed helical portion joined to a left-handed helical portion. In some embodiments, the first helical portion is joined to the second portion via a connecting member. In some embodiments, the connecting member is a linear connecting member.

[0039] In some embodiments, the nerve cuff comprises one or more electrodes configured to emit electrical pulses to a nerve. In some embodiments, the nerve cuff comprises one or more electrodes configured to detect electrophysiological signals transmitted by a nerve. In some embodiments, the nerve cuff comprises two or more electrodes configured to detect electrophysiological signals transmitted by a nerve. In some embodiments, the nerve cuff comprises one or more electrodes configured to detect electrophysiological signals transmitted by a nerve and one or more electrodes configured to emit electrical pulses to a nerve, and at least one of the one or more electrodes configured to emit electrical pulses to a nerve is wider than at least one of the one or more electrodes configured to detect electrophysiological signals transmitted by a nerve.

[0040] In some embodiments of the helical nerve cuff, the helical nerve cuff is configured to at least partially wrap fibrous tissue including the splenic nerve. In some embodiments of the helical nerve cuff, the helical nerve cuff is configured to at least partially wrap fibrous tissue including the splanchnic nerve.

[0041] Also described herein is a method of implanting a helical nerve cuff including one or more electrodes, the method including at least partially unwinding the helical nerve cuff, passing an end of the helical nerve cuff behind fibrous tissue including a nerve, and wrapping the helical nerve cuff around the fibrous tissue. In some embodiments, the helical nerve cuff is any one of the helical nerve cuffs described above.

[0042] Further described herein is a method of implanting an implantable device including a body having a wireless communication system and a helical nerve cuff having one or more electrodes, the method including at least partially unwinding the helical nerve cuff, passing an end of the helical nerve cuff behind fibrous tissue including a nerve, and wrapping the helical nerve cuff around the fibrous tissue. In some embodiments, the method further includes restricting movement of the body when an end of the helical nerve cuff passes behind the fibrous tissue. In some embodiments, the body is held in a substantially stable position by holding a handle portion attached to the helical nerve cuff in a position proximal to the body or to the handle portion attached to the body. In some embodiments, the implantable device is any one of the implantable devices described above.

[0043] In some embodiments of implanting the helical nerve cuff or the implantable device, the method includes pulling an end of the helical nerve cuff that passes behind the fibrous tissue.

[0044] In some embodiments of implanting the helical nerve cuff or the implantable device, the method includes orienting the helical nerve cuff substantially parallel to the fibrous tissue.

[0045] In some embodiments of implanting a helical nerve cuff or an implantable device, the helical nerve cuff is at least partially unwound by pulling on an end of the helical nerve cuff that passes behind the fibrous tissue. In some embodiments of implanting a helical nerve cuff or an implantable device, the helical nerve cuff is at least partially unwound before pulling on an end of the helical nerve cuff that passes behind the fibrous tissue.

[0046] In some embodiments of implanting a helical nerve cuff or an implantable device, an end of the helical nerve cuff passes from beneath the fibrous tissue and behind the fibrous tissue.

[0047] In some embodiments of implanting a helical nerve cuff or an implantable device, the method includes separating the fibrous tissue from the surrounding tissue. In some embodiments, the fibrous tissue is separated from the surrounding tissue by circumferentially incising a portion of the fibrous tissue.

[0048] In some embodiments of implanting a helical nerve cuff or an implantable device, an end of the helical nerve cuff that passes behind the fibrous tissue is pulled by pulling on a handle portion attached to the end of the helical nerve cuff.

[0049] In some embodiments of implanting a helical nerve cuff or an implantable device, the fibrous tissue includes the splenic nerve. In some embodiments of implanting a helical nerve cuff or an implantable device, the fibrous tissue includes the splanchnic nerve.

[0050] Also described herein is a method of fabricating an implantable device, the method including attaching a feedthrough to a housing, disposing a board assembly including a wireless communication system within the housing, attaching the housing to a first nerve cuff layer, attaching the first nerve cuff layer to a second nerve cuff layer including one or more electrodes, and electrically connecting one or more electrodes of the nerve cuff to the board assembly via the feedthrough. In some embodiments, the feedthrough is attached to the housing before the board assembly is disposed within the housing. In some embodiments, the feedthrough is attached to the board assembly before the board assembly is positioned within the housing. In some embodiments, the method includes sealing the housing. In some embodiments, the method includes attaching an acoustic window to the housing. In some embodiments, the acoustic window is attached to the open top of the housing after the board assembly is disposed within the housing. In some embodiments, the method includes assembling the acoustic window by attaching a foil to a frame. In some embodiments, the method includes filling the housing with an acoustically conductive material. In some embodiments, the acoustically conductive material is filled into the housing through a port on the housing, and the method includes sealing the port. In some embodiments, the method includes attaching a wireless communication system to the board assembly. In some embodiments, the wireless communication system includes one or more ultrasonic transducers. In some embodiments, the board assembly includes an integrated circuit electrically connected to the wireless communication system. In some embodiments, the housing is directly attached to the first nerve cuff layer. In some embodiments, an adhesive or fastener is used to attach the housing to the first nerve cuff layer. In some embodiments, the first nerve cuff layer is helical. In some embodiments, the method includes attaching one or more handle portions to the body, the first nerve cuff layer, the second nerve cuff layer, or between the first nerve cuff layer and the second nerve cuff layer.In some embodiments, the method includes creating a second nerve cuff by embedding one or more electrodes in a substrate material. In some embodiments, the method includes winding the second nerve cuff around a mandrel (shaft body) and attaching the second nerve cuff to a first nerve cuff while the second nerve cuff is wound around the mandrel.

Brief Description of the Drawings

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[0070] Described herein is a helical nerve cuff that includes one or more electrodes for stimulating a nerve and / or detecting an electrophysiological signal (such as an action potential or the absence of an action potential) transmitted by the nerve. Also described is an implantable device that includes a helical nerve cuff and a body configured to operate the helical nerve cuff. The body includes a wireless communication system that can wirelessly receive instructions from another device or wirelessly transmit information (such as information regarding the detected electrophysiological signal or other physiological characteristics) to another device. Also described are methods of implanting the helical nerve cuff and the implantable device, and methods of fabricating the helical nerve cuff and the implantable device.

[0071] The nerve cuff can include a helical substrate configured to at least partially surround a fibrous tissue that includes a nerve, and one or more electrodes disposed on an inner surface of the helical substrate (e.g., along a longitudinal direction). The helical nerve cuff can be implanted in a subject such that the electrodes are in electrical communication with the nerve. The electrodes may be configured to detect an electrophysiological signal transmitted by the nerve or to emit an electrical pulse to the nerve. In some embodiments, the nerve cuff includes a handle portion attached to the helical substrate, which may be used to facilitate implantation of the nerve cuff. The helical nerve cuff may be implanted in a small and / or difficult-to-access nerve of a patient, such as a splenic nerve or a visceral nerve, and the helical design of the nerve cuff allows for easier implantation.

[0072] The implantable device includes a body having a wireless communication system (which may include one or more ultrasonic transducers or one or more radio frequency (RF) antennas), two or more electrodes that communicate electrically with the wireless communication system, and a helical nerve cuff. The two or more electrodes are configured to detect electrophysiological signals transmitted by a nerve or to emit electrical pulses to a nerve, and one or more of the electrodes are disposed on the helical nerve cuff. The body may include a conductive housing, which may optionally be one of the electrodes.

[0073] The helical nerve cuff can be implanted in a subject by circumferentially incising a portion of the fibrous tissue that includes a nerve (which may further include a blood vessel, i.e., a neurovascular bundle), passing the end of the nerve cuff through the back side of the fibrous tissue, and rotating the helical nerve cuff to place the nerve cuff around the fibrous tissue. The helical nerve cuff may be attached to the body, and the device body may be disposed in front of the fibrous tissue when the cuff is disposed around the periphery of the fibrous tissue. When the helical nerve cuff includes a handle portion attached to the end of the helical nerve, the handle portion can be sutured through the back side of the fibrous tissue to guide the end of the helical nerve cuff through the back side of the fibrous tissue.

[0074] The handle portion attached to the helical nerve cuff enables careful manipulation of the nerve cuff in the small compartment space of the nerve when the nerve cuff is implanted. A surgical grasping tool can be used to grasp the handle portion and pass it through the back side of the circumferentially incised fibrous tissue. In some embodiments, the nerve cuff includes a second handle portion at the opposite end of the helical nerve cuff. Also, the second handle portion can be grasped by a surgical grasper to guide the nerve cuff to a predetermined position, unwind the helix during implantation, or rotate the helical nerve cuff to properly position the device.

[0075] <Definition> As used herein, the singular forms "a", "an", and "the" include plural references unless the context clearly dictates otherwise.

[0076] The term "about" or "substantially" as applied to a value or parameter herein includes (and describes) variations that are directed to that value or parameter itself. For example, a description referring to "about X" includes a description of "X".

[0077] It is understood that aspects and variations of the invention described herein include aspects and variations that "consist of" and / or "consist essentially of".

[0078] The terms "subject" and "patient" are used interchangeably herein to refer to a vertebrate.

[0079] The terms "treat", "treating", and "treatment" are used synonymously herein and refer to any action that provides a benefit to a subject afflicted with a disease state or condition, including amelioration of at least one symptom, inhibition, suppression, or elimination of a condition, delay in the progression of a disease or condition, delay in the recurrence of a disease or condition, or inhibition of a disease or condition.

[0080] Where a range of values is provided, it is to be understood that each intervening value, between the upper and lower limits of that range, and any other stated or intervening value in that stated range, is encompassed within the disclosure. Where the stated range includes upper or lower limits, ranges excluding either of those included limits are also included in the disclosure.

[0081] It should be understood that one, some, or all of the characteristics of the various embodiments described herein can be combined to form other embodiments of the invention. The section headings used herein are for organizational purposes only and should not be construed as limiting the subject matter described.

[0082] The features and preferences described above in connection with the "Embodiments" are separate preferences and are not limited to only that particular embodiment, but can be freely combined with features from other technically feasible embodiments to form preferred combinations of features. This description is presented to enable those skilled in the art to practice and use the present invention and is provided in the context of patent applications and their requirements. Various modifications to the described embodiments will be readily apparent to those skilled in the art, and the general principles herein may be applied to other embodiments. Accordingly, the present invention is not intended to be limited to the embodiments shown, but should be accorded the widest scope consistent with the principles and features described herein.

[0083] <Helical nerve cuff> The helical nerve cuff includes a helical substrate configured to at least partially wrap around a fibrous tissue including a nerve, and one or more electrodes disposed along the length of the helical substrate. The nerve cuff may optionally include one or more handle portions, for example, a handle portion attached to an end of the helical substrate.

[0084] The nerve cuff is configured to at least partially wrap around a fibrous tissue including a nerve. The fibrous tissue may include fibrous tissues such as blood vessels (e.g., neurovascular bundles) in addition to the nerve. For example, the splenic nerve is closely associated with the splenic artery, and the nerve cuff may be configured to at least partially enclose both the splenic nerve and the splenic artery. The inner diameter of the helical nerve cuff may be selected based on the diameter of the fibrous tissue, which may vary depending on the type of subject, the target nerve, or other anatomical differences within the subject (e.g., the size of the nerve within a particular subject). By way of example, the inner diameter may be from about 1 mm to about 8 mm in diameter (e.g., from about 1 mm to about 2 mm, from about 2 mm to about 3 mm, from about 3 mm to about 4 mm, from about 4 mm to about 5 mm, from about 5 mm to about 6 mm, from about 6 mm to about 7 mm, or from about 7 mm to about 8 mm).

[0085] The helical nerve cuff may be configured to wrap around the nerve at least one turn. For example, the helical nerve cuff can wrap around the nerve about 1 to about 4 turns, such as about 1 to about 1.3 turns, about 1.3 to about 1.7 turns, about 1.7 to about 2 turns, about 2 to about 2.5 turns, about 2.5 to about 3 turns, or about 3 to about 4 turns. In some embodiments, the helical nerve cuff is configured to wrap around the nerve about 1.5 turns.

[0086] The substrate of the nerve cuff is an elongated material wound in a helical shape. The helical substrate may have a substantially flat inner surface and / or a substantially flat outer surface. The width of the substrate may be substantially uniform and optionally may have tapered or rounded ends. The width of the substrate defines an edge, and the edges may or may not contact each other as the substrate is wound in a helical shape when the nerve cuff is in the relaxed position. For example, in some embodiments, a gap may or may not separate the turns of the substrate. In some embodiments, the substrate has a width that defines an inner surface, a first edge of the substrate, and a second edge of the substrate, and at least a portion of the first edge contacts at least a portion of the second edge when the nerve cuff is in the relaxed position. In some embodiments, the substrate has a width that defines an inner surface, a first edge of the substrate, and a second edge of the substrate, and the first edge does not contact the second edge when the nerve cuff is in the relaxed position.

[0087] The substrate of the helical nerve cuff is made of an insulating material that can be a biocompatible and / or elastomeric material. Exemplary substrate materials include, but are not limited to, silicone, silicone rubber, polydimethylsiloxane (PDMS), urethane polymers, poly(p-xylylene) polymers (such as poly(p-xylylene) polymers sold under the trade name PARYLENE®), or polyimides.

[0088] In some embodiments, the substrate of the helical nerve cuff may include two or more layers, which may be of the same material or different materials. The layers can include an inner layer that forms the inner surface of the helical nerve cuff and contacts the fibrous tissue, and an outer layer that forms the outer surface of the helical nerve cuff. The conductive material can be disposed between the inner layer and the outer layer that can form the electrodes of the helical nerve cuff. For example, the inner layer can include one or more openings on the inner surface to expose the conductive material that defines the electrodes. The separate inner and outer layers can further define the helical shape of the substrate. For example, the inner layer may be under higher tension than the outer layer when the helical nerve cuff is in a bent configuration, which forces the substrate to curl inward when the helical nerve cuff is in a relaxed configuration.

[0089] The width of the nerve cuff can depend on the length of the nerve cuff (i.e., the maximum distance along the axis running through the center of the helix between the two ends of the nerve cuff), the number of revolutions of the substrate, and the size of the gap between substrate revolutions (if any). In some embodiments, the length of the nerve cuff is from about 4 mm to about 20 mm (e.g., from about 4 mm to about 7 mm, from about 7 mm to about 10 mm, from about 10 mm to about 13 mm, from about 13 mm to about 16 mm, or from about 16 mm to about 20 mm). In some embodiments, the width (or inner width) of the substrate is from about 2 mm to about 8 mm (e.g., from about 2 mm to about 4 mm, from about 4 mm to about 6 mm, or from about 6 mm to about 8 mm).

[0090] The nerve cuff may be flexible to enable manipulation of the nerve cuff during implantation. For example, in some embodiments, a helical nerve cuff can be configured in a bent position by at least partially unwinding the helical nerve cuff and in a relaxed position by forming the helical nerve cuff into a helical configuration. FIG. 6A shows an exemplary helical nerve cuff in a bent position, where both the right-handed helix portion and the left-handed helix portion of the nerve cuff are joined together, and by pulling on the first handle portion and the second handle portion attached in one direction to either end of the right-handed helix portion and the left-handed helix portion, and pulling on the third handle portion attached to the joining member in the opposite direction, it is partially unwound. FIG. 6B shows the same helical nerve cuff as shown in FIG. 6A in a relaxed position.

[0091] The nerve cuff may include a right-handed helix portion, a left-handed helix portion, or both right-handed and left-handed helix portions. For example, in some embodiments, the nerve cuff may include a right-handed helix portion joined to a left-handed helix portion either directly or via a connecting member (which may be linear, curved, or hinged).

[0092] One or more electrodes of the nerve cuff may be disposed on the inner surface of the nerve cuff substrate, may not be coated, or may be coated with a conductive material (e.g., may be electroplated with poly(3,4-ethylenedioxythiophene) (PEDOT) polymer or other conductive polymer or metal to improve the electrical properties of the electrode). In some embodiments, one or more electrodes are point electrodes. In some embodiments, one or more electrodes may be elongated, for example, disposed along the length of the helical substrate. The electrodes can terminate before, at, or beyond the end of the substrate. One or more electrodes can be connected to feed-throughs on the helical nerve cuff, which enables the electrodes to be electrically connected to a body attached to the outer surface of the substrate or the outer surface of the nerve cuff.

[0093] The nerve cuff includes one or more electrodes, such as one, two, three, four, five, six, seven, eight, nine, ten or more electrodes. In some embodiments, one or more of the electrodes are configured to emit electrical pulses to the nerve. In some embodiments, the nerve cuff includes one, two, three, four, five, six, seven, eight, nine, ten or more electrodes configured to emit electrical pulses to the nerve. In some embodiments, one or more of the electrodes are configured to detect electrophysiological signals transmitted by the nerve. In some embodiments, the nerve cuff includes one, two, three, four, five, six, seven, eight, nine, ten or more electrodes configured to detect electrophysiological signals transmitted by the nerve. In some embodiments, one or more electrodes are configured to emit electrical pulses to the nerve and one or more electrodes are configured to detect electrophysiological signals transmitted by the nerve. In some embodiments, the electrodes configured to emit electrical pulses are wider than the electrodes configured to detect electrophysiological signals. The electrodes of a helical nerve cuff (having two or more electrodes) may be arranged alongside each other or in different directions along the length of the helical nerve cuff.

[0094] Optionally, one or more electrodes on the nerve cuff have a serpentine configuration, or one or more (e.g., two, three, four, or more) serpentine segments. FIG. 19B shows an example of an electrode 1908 having a first serpentine segment 1914a and a second serpentine segment 1914b separated by a non-serpentine segment 1916. The serpentine configuration of the electrode allows for increased flexibility of the electrode and the nerve cuff, which can be particularly beneficial when implanting the nerve cuff. Certain peripheral nerves, such as the splenic nerve, may require significant manipulation and bending of the nerve cuff during implantation and placement, and the serpentine configuration can reduce the likelihood of nerve cuff or electrode damage during implantation.

[0095] Any handle portion is configured to be grasped by a surgical grasping tool (e.g., forceps, hook, or other grasping or holding instrument) and may be useful for manipulating the helical nerve cuff during implantation. The handle portion may extend from the helical substrate or be partially embedded within the helical substrate and may be more flexible and / or thinner than the substrate to facilitate grasping of the handle portion and manipulation of the nerve cuff. The handle portion may include a loop, for example, by forming a loop within the handle portion or by attaching either end of the handle portion to the substrate. In some embodiments, the handle portion includes a flexible filament (such as a thread, string, cord, suture, or wire), which is optionally biodegradable when implanted within a subject. In some embodiments, the handle portion includes a bioabsorbable material such as polyglycolide, polydioxanone, polycaprolactone, or a copolymer thereof.

[0096] Any handle portion may be attached to the nerve cuff proximal to the end of the nerve cuff (e.g., at the tip of a helical nerve cuff). The nerve cuff may optionally include two or more handle portions. For example, the helical portion can include an additional handle portion proximal to the end opposite the helical substrate, and / or an additional handle portion proximal to the middle portion of the helical substrate. When the helical nerve cuff is attached to the body, as further discussed herein, one of the handle portions may be proximal or distal to the body. As an example, in some embodiments, the body is attached proximal to the first end of the helical nerve cuff and the handle is attached proximal to the second end of the helical nerve cuff. In some embodiments, the body is attached proximal to the first end of the helical nerve cuff and the handle portion is attached proximal to the first end of the helical nerve cuff. In some embodiments, the body is attached proximal to the first end of the helical nerve cuff, the first handle portion is attached proximal to the body, and the second handle portion is attached proximal to the second end of the helical nerve cuff. In some embodiments, the body is attached to the middle portion of the helical nerve cuff, the first handle portion is attached proximal to the first end of the helical nerve cuff, the second handle portion is attached proximal to the body, and optionally, the third handle portion is attached proximal to the second end of the helical nerve cuff.

[0097] Optionally, two or more handle portions attached to the nerve cuff are joined to each other. For example, the first handle portion includes a first end attached proximal to the first end of the helical nerve cuff, the second handle portion includes a first end attached proximal to the second end of the helical nerve cuff, and the second end of the first handle portion and the second end of the second handle portion are joined to each other. The first handle portion and the second handle portion may be attached to the helical nerve cuff separated by a radial angle of about 90° to about 180° (e.g., about 90° to about 120°, about 120° to about 150°, or about 150° to about 180°) around the helical axis.

[0098] FIG. 1A illustrates an exemplary helical nerve cuff, which can be part of an implantable device described herein. FIG. 1B shows the nerve cuff shown in FIG. 1A from a different angle. The nerve cuff 100 includes a helical substrate 102 that includes an outer layer 104 and an inner layer 106. The nerve cuff is configured to wrap around the nerve for approximately 1.5 turns, and the gap 114 separates the turns of the substrate. The substrate 102 is configured as a left-handed helix, although embodiments with a right-handed helix substrate are also contemplated. The elongated electrodes 108 are disposed on the inner surface of the helical substrate 102. The elongated electrodes 108 extend from the feed-through ports 110 and terminate at a position in front of the end 112 of the helical substrate 102. The electrodes 108 are between the outer layer 104 and the inner layer 106, and the inner layer 106 includes elongated notches that expose the electrodes 108 to the inner surface of the nerve cuff 100. In an alternative embodiment, the electrodes are disposed on top of the inner layer 106. FIGS. 1D and 1E show the helical nerve cuff of FIGS. 1A and 1B attached to a body having a housing 122. The housing 122 is attached to the outer surface of the helical nerve cuff substrate 102. The feed-through 124 passes through the feed-through port 110 and electrically connects the elongated electrodes 108 to the body.

[0099] FIG. 1C shows an exemplary helical nerve cuff similar to the nerve cuff shown in FIGS. 1A and 1B, further including a first handle portion 118 attached to the helical substrate 102 proximal to the first end 112 of the substrate 102 and a second handle portion 120 attached to the helical substrate 102 proximal to the second end 116 of the substrate 102. The first handle portion 118 and the second handle portion 120 are each flexible filaments that form loops, and each end of the filament is attached to the substrate 102. The ends of the filaments are embedded within the substrate 102 between the inner layer 106 and the outer layer 104. FIG. 1F shows the helical nerve cuff of FIG. 1C attached to a body having a housing 122. The housing 122 is attached to the outer surface of the helical nerve cuff substrate 102.

[0100] Figures 2A and 2B respectively show front and rear perspective views of another embodiment of the helical nerve cuff 200. The nerve cuff 200 includes a substrate 202 having a left-handed helical segment 204 and a right-handed helical segment 206 joined to each other via a connecting member 208. The connecting member 208 of the illustrated nerve cuff 200 is a curved and elongated portion of the substrate 202 that rotates slightly less than one full rotation around the nerve. Feed-through ports 210 are disposed along the connecting member 208, whereby the body can be electrically connected to electrodes disposed on the inner surface of the substrate. The substrate 202 includes an outer layer 212 and an inner layer 214, and has conductivity with a conductive intermediate layer 216 sandwiched between the outer layer 212 and the inner layer 214. The helical nerve cuff includes three parallel and elongated electrodes (218, 220, and 222) configured to detect electrophysiological signals transmitted by the nerve on the inner surface of the substrate 202 in the left-handed helical segment 204, and a fourth elongated electrode 224 configured to emit electrical pulses to the nerve on the inner surface of the substrate 202 in the right-handed helical segment 206. The electrodes are defined by openings in the inner layer 214. In the illustrated embodiment, the fourth elongated electrode 224 is wider than the electrodes 218, 220, and 222. Figure 2C shows the helical nerve cuff of Figures 2A and 2B attached to a body having a housing 226. The housing 226 is attached to the outer surface of the substrate 202 of the helical nerve cuff at the connecting member 208. The feed-through 228 passes through the feed-through port 210 where it electrically connects the electrodes 218, 220, 222, and 224 to the body.

[0101] Figures 3A and 3B respectively show front and bottom perspective views of another embodiment of the helical nerve cuff 300. The nerve cuff 300 includes a substrate 302 having a left-handed helical segment 304 and a right-handed helical segment 306 joined to each other via a connecting member 308. The connecting member 308 of the illustrated nerve cuff 300 is a curved and elongated portion of the substrate 302 and is shorter than the connecting members of the nerve cuffs illustrated in FIGS. 2A and 2B. The feed-through ports 310 are disposed along the connecting member 308, whereby the body can be electrically connected to electrodes disposed on the inner surface of the substrate. The substrate 302 of the illustrated nerve cuff 300 includes a single layer having electrodes disposed along the inner surface of the substrate 302. The helical nerve cuff includes three elongated electrodes (312, 314, and 316) on the inner surface of the substrate 302 in the left-handed helical segment 304 and a fourth elongated electrode 318 on the inner surface of the substrate 302 in the right-handed helical segment 306. FIG. 3C shows the helical nerve cuff of FIGS. 3A and 3B attached to a body having a housing 320. The housing 320 is attached to the outer surface of the helical nerve cuff substrate 302.

[0102] Figures 4A and 4B show, respectively, a bottom view and a top view of another embodiment of the helical nerve cuff 400. The nerve cuff 400 includes a substrate 402 having a left-handed helical segment 404 and a right-handed helical segment 406 joined to each other via a connecting member 408. The connecting member 408 of the illustrated nerve cuff 400 is an elongated straight connecting member. The feed-through port 410 is disposed along the connecting member 408, thereby enabling the body to be electrically connected to the electrodes disposed on the inner surface of the substrate. The substrate 402 of the illustrated nerve cuff 400 includes a single layer having electrodes disposed along the inner surface of the substrate 402. The helical nerve cuff includes three parallel elongated electrodes (412, 414, and 416) on the inner surface of the substrate 402 in the left-handed helical segment 404, extending beyond the end 418 of the nerve cuff 400. In the illustrated embodiment, the electrodes 412, 414, and 416 are joined to each other at the joining end 420. The nerve cuff further includes a fourth elongated electrode 422 on the inner surface of the substrate 402 in the right-handed helical segment 406, which extends beyond the opposite end 424 of the nerve cuff 400.

[0103] Figures 5A and 5B show, respectively, a bottom view and a top view of another embodiment of the helical nerve cuff 500. The nerve cuff 500 includes a substrate 502 having a first left-handed helical segment 504 and a second left-handed helical segment 506 joined to each other via a connecting member 508. The connecting member 508 of the illustrated nerve cuff 500 is an elongated straight connecting member. A feed-through port 510 is disposed along the connecting member 508, thereby enabling the body to be electrically connected to electrodes disposed on the inner surface of the substrate. The substrate 502 of the illustrated nerve cuff 500 includes a single layer having electrodes disposed along the inner surface of the substrate 502. The helical nerve cuff includes three parallel elongated electrodes (512, 514, and 516) on the inner surface of the substrate 502 in the first left-handed helical segment 504, extending beyond the end 518 of the nerve cuff 500. The nerve cuff further includes a fourth elongated electrode 520 on the inner surface of the substrate 502 in the second left-handed helical segment 506, extending beyond the end 522 of the nerve cuff 500 on the opposite side.

[0104] The helical nerve cuff can optionally include a mount configured to receive the body. The mount provides additional stability to the device so that the body does not come off the helical nerve cuff. The mount can be attached to the substrate of the helical nerve cuff, for example, on the outer surface of the helical nerve cuff or at the end of the helical nerve cuff. The mount can include a substrate receiving port sized and shaped to receive an end of the substrate of the helical nerve cuff. One or more electrodes of the helical nerve cuff may extend beyond the end of the substrate so that they can be disposed deeper within the substrate receiving port than within the substrate itself. The mount can also include a body receiving port sized and shaped to receive a body or housing that houses the body. Thus, the mount can provide a stable attachment of the body to the substrate of the helical nerve cuff. As further described herein, the body can include components for operating one or more electrodes on the helical nerve cuff. Thus, the mount provides an electrical connection between the body and one or more electrodes of the helical nerve cuff. This can occur, for example, by enabling a direct connection between one or more electrodes of the helical nerve cuff and the body. For example, the mount can include an opening that connects the substrate receiving port and the body receiving port to enable an electrical connection between the body and one or more electrodes. Alternatively, the mount can include one or more electrical feedthroughs that are intermediate the electrical connection between the body and one or more electrodes on the helical nerve cuff.

[0105] The mount can be made of an insulating material that can be a biocompatible and / or elastomeric material. Exemplary materials for the mount include, but are not limited to, silicon, silicone rubber, polyetheretherketone (PEEK), polydimethylsiloxane (PDMS), urethane polymers, poly(p-xylylene) polymers (such as poly(p-xylylene) polymers sold under the trade name PARYLENE®), or polyimide.

[0106] Figures 19A - 19C show an exemplary helical nerve cuff having a mount 1902 configured to receive a body 1904 attached to a substrate 1906. The substrate 1906 is shown as transparent so that the electrodes 1908 on the inner surface of the helical substrate can be seen. Referring to FIG. 19C, the mount 1902 includes a substrate receiving port 1920 and a body receiving port 1918. As shown in FIG. 19B, the substrate 1906 may include a terminal 1912 that can be received by the substrate receiving port 1920 of the mount 1902. The electrode 1908 can include an extension 1910 that extends beyond the terminal 1912 of the substrate 1906. When the mount is attached to the substrate, the extension 1910 of the electrode 1908 is disposed at a position deeper within the substrate receiving port 1920 than the terminal 1912 (see FIG. 19A). By attaching the body 1904 through the body receiving port 1918, an electrical connection between the body 1904 and the electrode 1908 is enabled through the extension 1910 of the electrode 1908.

[0107] In some embodiments, the helical nerve cuff 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). The helical nerve cuff may be configured to at least partially wrap around a fibrous tissue (such as a peripheral nerve or a fibrous tissue including a peripheral nerve such as a neurovascular bundle) within any of these animals or other animals. For example, in some embodiments, the helical nerve cuff is configured to at least partially wrap around a human peripheral nerve such as the human splenic nerve or the human splenic neurovascular bundle. In some embodiments, the helical nerve cuff is configured to at least partially wrap around a human peripheral nerve such as the human splanchnic nerve. In some embodiments, the helical nerve cuff is configured to at least partially wrap around an autonomic nerve. In some embodiments, the nerve is a sympathetic nerve. 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.

[0108] <Implantable Device> An implantable device that can be used to detect electrophysiological signals transmitted by nerves and emit electrical pulses to nerves can include a body attached to a helical nerve cuff. The body is attached to the helical nerve cuff without a lead that mediates between the body and the helical nerve cuff. That is, the body adheres directly to the outer surface of the helical nerve cuff to join the body to the nerve cuff. By fixing the body to the helical nerve cuff, the nerve cuff and the body can be positioned simultaneously during implantation. The body can include a wireless communication system electrically connected to two or more electrodes. The two or more electrodes can be configured to detect electrophysiological signals transmitted by nerves or emit electrical pulses to nerves, and at least one of the electrodes is included in the helical nerve cuff. The helical nerve cuff can be, for example, a helical nerve cuff as described in more detail herein. The implantable device is completely implantable, that is, no wires or leads are connected to the outside of the subject's body after implantation.

[0109] Two or more electrodes of the device include one or more electrodes on the helical nerve cuff and are electrically connected to the wireless communication system. The body of the device may further include an integrated circuit, and the electrodes are connected to the wireless communication system via the integrated circuit. The integrated circuit can be configured to operate the wireless communication system of the device body and operate two or more electrodes of the implantable device to detect electrophysiological signals and / or emit electrical pulses. Optionally, the implantable device includes one or more sensors (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 the concentration of a specimen) configured to detect a physiological state.

[0110] The body of the implantable device includes a wireless communication system that can communicate with a separate device (such as an external interrogator or another implantable device). For example, the wireless communication can be configured to receive instructions for emitting one or more electrical pulses to a nerve and / or transmit information such as data related to detected electrophysiological signals transmitted by the nerve and / or data related to one or more physiological conditions (such as the specimen's pulse, temperature, pressure, presence or concentration, etc.). The wireless communication system can include, for example, one or more ultrasonic transducers or one or more radio frequency antennas. Also, the wireless communication system can be configured to receive energy from another device (such as via ultrasound or radio frequency (RF)), and this energy can be used to power the implantable device.

[0111] Information regarding the detected electrophysiological signal or physiological state can be transmitted to a receiving device using the wireless communication system. For example, the wireless communication system can include two or more ultrasonic transducers that operate to encode information regarding the detected electrophysiological signal or physiological state using ultrasonic backscattered waves or radio frequency backscattered waves. Exemplary implantable devices that can detect electrophysiological signals and encode information related to the detected electrophysiological signals are described in International Publication No. WO 2018 / 009910 pamphlet. Exemplary implantable devices that can be operated using ultrasound to emit electrical pulses are described in WO 2018 / 009912 A2. Exemplary implantable devices that can be powered by ultrasound and emit ultrasonic backscatter that encodes the detected physiological state are described in WO 2018 / 009905 A2 and WO 2018 / 009911 A2.

[0112] The integrated circuit included in the device body can electrically connect and communicate between an electrode or sensor and a wireless communication system (e.g., one or more ultrasonic transducers or one or more RF antennas). The integrated circuit can include or operate a modulation circuit within the wireless communication system that modulates the current flowing through the wireless communication system (e.g., one or more ultrasonic transducers or one or more radio frequency antennas) to encode information in the current. The modulated current affects the backscattered waves (e.g., ultrasonic backscattered waves or radio frequency backscattered waves) radiated by the wireless communication system, and the backscattered waves encode the information.

[0113] FIG. 7 shows a side view of a board assembly of an exemplary implantable device body, which may be surrounded by a housing and may be attached to a helical nerve cuff. The body includes a wireless communication system (e.g., an ultrasonic transducer) 702 and an integrated circuit 704. In the illustrated embodiment, the integrated circuit 704 includes a power circuit including a capacitor 706. In the illustrated embodiment, the capacitor is an “off-chip” capacitor (in that it is not on the integrated circuit chip), but is still electrically integrated within the circuit. The capacitor can temporarily store electrical energy converted from energy (e.g., ultrasonic) received by the wireless communication system and can be operated by the integrated circuit 704 to store or release energy. Optionally, the body further includes a sensor 708 configured to detect a physiological state. The ultrasonic transducer 702, the integrated circuit 704, the capacitor 706, and the optional sensor 708 are mounted on a circuit board 710, which may be a printed circuit board. The circuit board 710 can further include one or more feedthroughs 712a, 712b, 712c, and 712d that electrically connect the circuit board and / or the integrated circuit to one or more electrodes of the helical nerve cuff. The wireless communication system 702 is electrically connected to the integrated circuit 704, and the integrated circuit 704 is electrically connected to the electrodes via the feedthroughs 712a, 712b, 712c, and 712d, thereby electrically connecting the wireless communication system 702 to the electrodes.

[0114] A wireless communication system can be configured to receive instructions for operating an implantable device. The instructions may be transmitted, for example, by a separate device such as an interrogator. As an example, ultrasonic waves received by the implantable device (e.g., ultrasonic waves transmitted by the interrogator) can encode instructions for operating the implantable device. In another example, RF waves received by the implantable device can encode instructions for operating the implantable device. The instructions can include, for example, a trigger signal that instructs the implantable device to emit an electrical pulse through the electrodes of the device. The trigger signal can include information, for example, regarding when the electrical pulse should be emitted, the pulse frequency, the pulse power or voltage, the pulse shape, and / or the pulse duration.

[0115] In some embodiments, the implantable device can also be operated to transmit information (i.e., uplink communication) that can be received by the interrogator via the wireless communication system. In some embodiments, the wireless communication system is configured to actively generate a communication signal (e.g., ultrasonic or radio frequency) that encodes the information. In some embodiments, the wireless communication system is configured to transmit information encoded on a backscatter wave (e.g., an ultrasonic backscatter wave or an RF backscatter wave). Backscatter communication provides a low-power method of transmitting information, which is particularly beneficial for small devices in order to minimize energy issues. As an example, the wireless communication system can include one or more ultrasonic transducers configured to emit an ultrasonic backscatter that can receive ultrasonic waves and encode information transmitted by the implantable device. A current can flow through the ultrasonic transducer and can be modulated to encode the information. The current can be modulated, for example, directly by passing the current through a sensor that modulates the current, or indirectly by using a modulation circuit to modulate the current based on, for example, a detected physiological state or an electrophysiological pulse.

[0116] In some embodiments, the information transmitted by the wireless communication system includes information not related to the physiological state detected or the electrophysiological pulses detected by the implantable device. For example, the information can include information related to the state of the implantable device, or a confirmation signal to confirm that an electrical pulse has been emitted, power, frequency, voltage, duration, or other information related to the emitted electrical pulse, and / or one or more of the identification codes of the implantable device. Optionally, the integrated circuit is configured to digitize the information, and the wireless communication system can transmit the digitized information.

[0117] The information wirelessly transmitted using the wireless communication system can be received by an interrogator. In some embodiments, the information is transmitted by being encoded with a backscatter (e.g., an ultrasonic backscatter or a radio frequency backscatter). The backscatter can be received, for example, by an interrogator and decoded to determine the encoded information. Further details regarding backscatter communication are provided herein, and additional examples are provided in WO 2018 / 009905, WO 2018 / 009908, WO 2018 / 009910, WO 2018 / 009911, WO 2018 / 009912, International Patent Application No. PCT / US2019 / 028381, International Patent Application No. PCT / US2019 / 028385, and International Patent Application No. PCT / 2019 / 048647, each of which is hereby incorporated by reference in its entirety for all purposes. This information can be encoded by the integrated circuit using a modulation circuit. The modulation circuit is part of the wireless communication system and can be operated by the integrated circuit or housed within the integrated circuit.

[0118] The interrogator can transmit an energy wave (e.g., ultrasonic or radio frequency), and the energy wave is received by the wireless communication system of the device to generate a current flowing through the wireless communication system (e.g., generate a current flowing through an ultrasonic transducer or a radio frequency antenna). Then, the flowing current can generate a backscatter radiated by the wireless communication system. The modulation circuit can be configured to modulate the current flowing through the wireless communication system to encode information. For example, the modulation circuit may be electrically connected to an ultrasonic transducer that receives ultrasonic waves from the interrogator. The current generated by the received ultrasonic waves can be modulated using the modulation circuit to encode information, and as a result, the ultrasonic backscatter wave radiated by the ultrasonic transducer encodes the information. A similar approach can be taken with a radio frequency antenna that receives radio frequencies. The modulation circuit includes one or more switches such as an on / off switch or a field effect transistor (FET). An exemplary FET that can be used with some embodiments of the implantable device is a metal-oxide-semiconductor field effect transistor (MOSFET). The modulation circuit can change the impedance of the current flowing through the wireless communication system, and the variation of the current flowing through the wireless communication system encodes information. In some embodiments, the information encoded in the backscatter wave includes information related to an electrophysiological signal transmitted by a nerve, an electrical pulse emitted by the implantable device, or a physiological state detected by a sensor of the implantable device. In some embodiments, the information encoded in the backscatter wave includes a unique identifier of the implantable device. This can be useful, for example, to ensure that the interrogator communicates with the correct implantable device when a plurality of implantable devices are implanted in a subject. In some embodiments, the information encoded in the backscatter wave includes a verification signal that verifies an electrical pulse emitted by the implantable device.In some embodiments, the information encoded in the backscattered wave includes the amount of energy or voltage stored in an energy storage circuit (or one or more capacitors within the energy storage circuit). In some embodiments, the information encoded in the backscattered wave includes the impedance detected. Changes in the impedance measurements can identify scar tissue or the degradation of the electrodes over time.

[0119] In some embodiments, the modulation circuit operates using a digital circuit or a mixed-signal integrated circuit (which may be part of an integrated circuit) that can actively encode information with a digitized signal or an analog signal. The digital circuit or the mixed-signal integrated circuit can include a 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 ultrasonic communication between the interrogator and the implantable device. In some embodiments, the digital circuit or the mixed-signal integrated circuit includes an analog / digital converter (ADC) that can convert an analog signal encoded with ultrasonic waves emitted from the interrogator so that the signal can be processed by the digital circuit or the mixed-signal integrated circuit. Also, the digital circuit or the mixed-signal integrated circuit can operate a power circuit, for example, to generate an electrical pulse to stimulate tissue. In some embodiments, the digital circuit or the mixed-signal integrated circuit receives a trigger signal encoded with ultrasonic waves transmitted by the interrogator and operates the power circuit to discharge an electrical pulse in response to the trigger signal.

[0120] In some embodiments, a wireless communication system includes one or more ultrasonic transducers, such as one, two, or three or more ultrasonic transducers. In some embodiments, the wireless communication system includes a first ultrasonic transducer having a first polarization axis and a second ultrasonic transducer having a second polarization axis, and the second ultrasonic transducer is positioned such that the second polarization axis is orthogonal to the first polarization axis, and the first ultrasonic transducer and the second ultrasonic transducer are configured to supply power to the device and receive ultrasonic waves that emit ultrasonic backscatter. In some embodiments, the wireless communication system 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, and the second ultrasonic transducer is positioned such that the second polarization axis is orthogonal to the first polarization axis and the third polarization axis, and the third ultrasonic transducer is positioned such that the third polarization axis is orthogonal to the first polarization and the second polarization axes, and the first ultrasonic transducer and the second ultrasonic transducer are configured to supply power to the device and receive ultrasonic waves that emit ultrasonic backscatter. FIG. 8 is a diagram showing a board assembly of a main body of a device including two orthogonally arranged ultrasonic transducers. The main body includes a circuit board 802 such as a printed circuit board and an integrated circuit 804 that is a power circuit including a capacitor 806. The main body further includes a first ultrasonic transducer 808 electrically connected to the integrated circuit 804 and a second ultrasonic transducer 810 electrically connected to the integrated circuit 804. The first ultrasonic transducer 808 includes a first polarization axis 812, and the second ultrasonic transducer 810 includes a second polarization axis 814. The first ultrasonic transducer 808 and the second ultrasonic transducer are arranged such that the first polarization axis 812 is orthogonal to the second polarization axis 814.

[0121] When included in a wireless communication system, the ultrasonic transducer may be a micromachined ultrasonic transducer such as a capacitive micromachined ultrasonic transducer (CMUT) or a piezoelectric micromachined ultrasonic transducer (PMUT), or it may be a bulk piezoelectric transducer. The bulk piezoelectric transducer can be made of any natural or synthetic material such as quartz, ceramic, or polymer. Exemplary bulk piezoelectric transducer materials include barium titanate (BaTiO3), lead zirconate titanate (PZT), zinc oxide (ZO), aluminum nitride (AlN), quartz, berlinite (AlPO4), topaz, langasite (La3Ga5SiO14), gallium orthophosphate (GaPO4), lithium niobate (LiNbO3), lithium tantalate (LiTaO3), potassium niobate (KNbO3), sodium tungstate (Na2WO3), bismuth ferrite (BiFeO3), polyvinylidene fluoride (dii) (PVDF), and lead magnesium niobate-lead titanate (PMN-PT).

[0122] In some embodiments, the bulk piezoelectric transducer is approximately cubic (i.e., an aspect ratio of approximately 1:1:1 (length:width:height)). In some embodiments, the piezoelectric transducer is plate-shaped with an aspect ratio of approximately 5:5:1 or greater in either the length or width aspect, such as approximately 7:5:1 or greater, or approximately 10:10:1 or greater. In some embodiments, the bulk piezoelectric transducer is long and narrow with an aspect ratio of approximately 3:1:1 or greater, and the longest dimension is aligned with the direction of the ultrasonic backscattered wave (i.e., the polarization axis). In some embodiments, one dimension of the bulk piezoelectric transducer is equal to 1 / 2 of the wavelength (λ) corresponding to the driving frequency or resonance frequency of the transducer. At the resonance frequency, the ultrasonic waves impinging on either surface of the transducer undergo a 180° phase shift to reach the opposite phase, causing the maximum displacement between the two surfaces. In some embodiments, the height of the piezoelectric transducer is from approximately 10 μm to approximately 1000 μm (such as approximately 40 μm to approximately 400 μm, approximately 100 μm to approximately 250 μm, approximately 250 μm to approximately 500 μm, or approximately 500 μm to approximately 1000 μm). In some embodiments, the height of the piezoelectric transducer is 5 mm or less (such as 4 mm or less, 3 mm or less, 2 mm or less, 1 mm or less, 500 μm or less, 400 μm or less, 250 μm or less, 100 μm or less, or 40 μm or less). In some embodiments, the height of the piezoelectric transducer is such that the length is 20 μm or greater (such as 40 μm or greater, 100 μm or greater, 250 μm or greater, 400 μm or greater, 500 μm or greater, 1 mm or greater, 2 mm or greater, 3 mm or greater, or 4 mm or greater). In some embodiments, the ultrasonic transducer has a length of 5 mm or less in the longest dimension, such as 4 mm or less, 3 mm or less, 2 mm or less, 1 mm or less, 500 μm or less, 400 μm or less, 250 μm or less, 100 μm or less, or 40 μm or less. In some embodiments, the ultrasonic transducer has a length of 20 μm or greater (such as 40 μm or greater, 100 μm or greater, 250 μm or greater, 400 μm or greater, 500 μm or greater, 1 mm or greater, 2 mm or greater, 3 mm or greater, or 4 mm or greater) in the longest dimension.

[0123] When included in a wireless communication system, an ultrasonic transducer can connect two electrodes to enable electrical communication with an integrated circuit. The first electrode is attached to the first surface of the transducer, the second electrode is attached to the second surface of the transducer, and the first and second surfaces are opposite side surfaces 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 orthogonal to the movement of the transducer.

[0124] An implantable device may be configured to wirelessly receive energy and convert that energy into electrical energy, which may be used to power the device. A wireless communication system may be used to wirelessly receive energy, or a separate system may be configured to receive energy. For example, an ultrasonic transducer (which may be an ultrasonic transducer housed within the wireless communication system or a different ultrasonic transducer) may be configured to receive ultrasonic waves and convert the energy from the ultrasonic waves into electrical energy. In some embodiments, an RF antenna (which may be an RF antenna housed within the wireless communication system or a different RF antenna) is configured to receive RF waves and convert the energy from the RF waves into electrical energy. The electrical energy is transmitted to an integrated circuit to power the device. The electrical energy can directly power the device or operate a power circuit to store energy for later use by the integrated circuit.

[0125] In some embodiments, the integrated circuit includes a power circuit that can include an energy storage circuit. The energy storage circuit may be a battery or an alternative energy storage device such as one or more capacitors. The implantable device is preferably battery - less and may instead rely on one or more capacitors. As an example, energy from ultrasound or radio frequency received by the implantable device (e.g., through a wireless communication system) can be converted into an electric current and stored in the energy storage circuit. The energy can be used to operate the implantable device, such as to power a digital circuit, a modulation circuit, or one or more amplifiers, or can be used to generate electrical pulses for stimulating tissue. In some embodiments, the power circuit further includes, for example, a rectifier and / or a charge pump.

[0126] The integrated circuit may be configured to detect electrophysiological signals transmitted by nerves or to operate two or more electrodes of a device configured to emit electrical pulses to nerves, with at least one of the electrodes being included on a helical nerve cuff. The electrodes may be disposed on the helical nerve cuff, on the body of the device, or both (e.g., one or more electrodes may be on the body of the device and one or more electrodes may be on the helical nerve cuff). In some embodiments, the housing of the body operates as an electrode. For example, the device may include one or more active electrodes on the helical nerve cuff and the housing may be configured as a counter - electrode. Thus, in some embodiments, the housing of the device is electrically connected to the integrated circuit. The one or more electrodes on the helical nerve cuff are electrically connected to the integrated circuit, for example, through one or more feed - throughs.

[0127] In some embodiments, the implantable device includes one or more sensors configured to detect physiological conditions. The sensors may be included, for example, as part of the body of the device or on a helical nerve cuff. The sensors are configured to detect physiological conditions such as temperature, oxygen concentration, pH, analyte (such as glucose), strain, or pressure. Variations in physiological conditions modulate impedance, which in turn modulates the current flowing through a detection circuit that is either electrically connected to or part of an integrated circuit. The implantable device can comprise one or more (such as 2, 3, 4, 5 or more) sensors that can detect the same physiological condition or different physiological conditions. In some embodiments, the implantable device comprises 10, 9, 8, 7, 6, or 5 or fewer sensors. For example, in some embodiments, the implantable device comprises a first sensor configured to detect temperature and a second sensor configured to detect oxygen. Changes in both physiological conditions can be encoded in backscattered waves emitted by a wireless communication system, which can be decoded by an external computing system (such as an interrogator).

[0128] The body of the implantable device is attached to the helical nerve cuff, for example, on the outer surface of the helical nerve cuff. In some embodiments, the body is attached to the end of the helical nerve cuff or to an intermediate portion of the helical nerve cuff. Optionally, the handle portion can be attached to the helical nerve cuff and can be attached at a position proximal to the body. In some embodiments, the implantable device includes a handle portion attached to the helical nerve cuff at a position proximal to the body of the implantable device attached to the helical nerve cuff and a second handle portion attached to the helical nerve cuff at a distal position such as the end of the helical nerve cuff. Examples of implantable device bodies attached to helical nerve cuffs are shown in FIGS. 1D, 1E, 1F, 2C, and 3C. In some embodiments, the handle portion is attached to the body of the implantable device.

[0129] The body (or housing) of the implantable device may be attached to the helical nerve cuff via an adhesive (e.g., epoxy, glue, cement, solder, or other binder), one or more fasteners (e.g., staples, screws, bolts, clamps, rivets, pins, rods, etc.), or any other suitable means for securely attaching the body to the helical nerve cuff so that it does not separate from the nerve cuff after implantation. The body (or housing) can be attached directly to the nerve cuff. FIG. 9 shows an exemplary body 902 attached to a nerve cuff 904 using fasteners (906 and 908). In some embodiments, the body has an elongated shape, with one end of the body (i.e., the attachment end) attached to the helical nerve cuff and the opposite end (i.e., the extension end) extending from the nerve cuff (see, e.g., the body attached to the nerve cuff in FIG. 1E).

[0130] The body can include a housing, which can include a base, one or more sidewalls, and a top. The housing can optionally be made of a conductive material and configured as one of one or more electrodes of an implantable device configured to detect electrophysiological signals transmitted by a nerve or to emit electrical pulses to a nerve. For example, the housing of the body may be configured as a counter electrode, and one or more electrodes on the helical nerve cuff may be configured as working electrodes. The housing is made of a biocompatible material such as a biocompatible metal (e.g., steel or titanium) or a biocompatible ceramic (e.g., titania or alumina). The housing is preferably sealed to prevent body fluid from entering the body.

[0131] An acoustic window can be included in the housing of the body, for example, in the upper part of the housing (see FIG. 10). The acoustic window is a thinner material (such as foil) that allows acoustic waves to penetrate the housing so that the acoustic waves can be received by one or more ultrasonic transducers within the body of the implantable device. In some embodiments, the housing (or the acoustic window of the housing) may be thin to allow ultrasonic waves to penetrate the housing, and the thickness is about 100 micrometers (μm) or less, such as about 75 μm or less, about 50 μm or less, about 25 μm or less, about 15 μm or less, or about 10 μm or less. In some embodiments, the thickness of the housing (or the acoustic window of the housing) is about 5 μm to about 10 μm, about 10 μm to about 15 μm, about 15 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.

[0132] The housing may be filled with an acoustically conductive material such as a polymer or an oil (such as silicone oil). Data can fill the empty space within the housing to reduce the acoustic impedance mismatch between the outside of the housing and the tissue within the housing. Therefore, the body of the device preferably has no air or vacuum. The housing can include a port, for example, on the side wall of the housing (see FIG. 10), so that the housing can be filled with an acoustically conductive material. Once the housing is filled with the material, the port can be sealed to avoid leakage of the material after implantation.

[0133] The housing of the implantable device is relatively small, enabling comfortable long-term implantation while limiting the inflammation of tissues often associated with implantable devices. In some embodiments, the longest dimension of the device housing is about 8 mm or less, about 7 mm or less, about 6 mm or less, 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, or about 0.1 mm or less in length. In some embodiments, the longest dimension of the device housing 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, about 3 mm or more, about 4 mm or more, about 5 mm or more, about 6 mm or more, or about 7 mm or more at the longest dimension of the device. In some embodiments, the longest dimension of the device housing is about 0.3 mm to about 8 mm, about 1 mm to about 7 mm, about 2 mm to about 6 mm, or about 3 mm to about 5 mm in length. In some embodiments, the housing of the implantable device is about 10 mm 3 or less (e.g., about 8 mm 3 or less, 6 mm 3 or less, 4 mm 3 or less, or 3 mm 3 or less) in volume. In some embodiments, the housing of the implantable device is about 0.5 mm 3 to about 8 mm, about 1 mm 3 to about 7 mm, about 2 mm 3 to about 6 mm, or about 3 mm 3 to about 5 mm in volume.

[0134] The housing (such as the bottom of the housing) can include a feed-through port that can be aligned with the feed-through port of the nerve cuff. The feed-through can electrically connect one or more electrodes of the nerve cuff to components of the body within the housing. For example, the feed-through may be electrically connected to an integrated circuit and / or the wireless communication system of the device body. FIG. 11A shows a housing 1102 having a feed-through port 1104, and FIG. 11B shows a housing having a feed-through 1106 arranged to electrically connect components of the body to one or more electrodes of a helical nerve cuff. FIG. 11C shows a cross-sectional view of an exemplary device, where the feed-through 1106 electrically connects an electrode 1108 on the nerve cuff to an electronic circuit 1110 (such as an integrated circuit, a wireless communication system, etc.) disposed within the housing 1102 of the body. The feed-through can be, for example, a metal (such as a metal including silver, copper, gold, platinum, platinum black, or nickel), sapphire, or a conductive ceramic (such as indium tin oxide (ITO)). The electrodes can be connected to the feed-through using any suitable means such as soldering, laser welding, or crimping the feed-through to the electrode.

[0135] In some embodiments, an 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). The helical nerve cuff may be configured to at least partially wrap around any of these animals or around fibrous tissue (such as a peripheral nerve or fibrous tissue including a peripheral nerve such as a neurovascular bundle) within other animals. For example, in some embodiments, the helical nerve cuff is configured to at least partially wrap around a human splenic nerve or a human peripheral nerve such as a human splenic neurovascular bundle. In some embodiments, the helical nerve cuff is configured to at least partially wrap around an autonomic nerve. In some embodiments, the nerve is a sympathetic nerve. 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.

[0136] <Interrogator> The interrogator can communicate wirelessly with one or more implantable devices using the wireless communication system of the implantable device. Wireless communication may include receiving information wirelessly from the implantable device, transmitting instructions wirelessly to the implantable device (such as a trigger signal instructing the implantable device to emit an electrical pulse), or both. For example, in some embodiments, the interrogator transmits ultrasonic waves that encode instructions for operating the device, such as a trigger signal instructing the implantable device to emit an electrical pulse. In some embodiments, the interrogator further receives ultrasonic backscatter from the implantable device that encodes information transmitted by the implantable device. The information can include, for example, detected electrophysiological pulses, electrical pulses emitted by the implantable device, and / or information related to a measured physiological state.

[0137] In some embodiments, the interrogator wirelessly transmits energy (such as ultrasonic or radio frequency) to power the implantable device. For example, the interrogator can transmit ultrasonic or RF waves to the implantable device, and the implantable device can convert the energy from the received waves into electrical energy that is used to power the device immediately or by storing the energy in a power circuit.

[0138] The interrogator can include one or more ultrasonic transducers or radio frequency antennas (e.g., depending on whether the implantable device includes an ultrasonic transducer or radio frequency antenna within its wireless communication system) that can operate as transmitters and / or receivers (or transceivers that can alternatively transmit or receive ultrasonic). The one or more transducers can be arranged as an array (e.g., a transducer array), and the interrogator can optionally include one or more arrays. In some embodiments, the transmit function is separated from the receive function on a separate device. That is, optionally, the interrogator includes a first device that transmits ultrasonic or RF waves to the implantable device and a second device that receives ultrasonic or RF backscatter from the implantable device. In some embodiments, the transducers or RF antennas within the array can have regular spacing, irregular spacing, or can be sparsely arranged. In some embodiments, the array is flexible. In some embodiments the array is planar and in some embodiments the array is non-planar.

[0139] An exemplary interrogator is shown in FIG. 12. The illustrated interrogator shows a transducer array having a plurality of ultrasonic transducers. In some embodiments, the transducer array includes one or more, two or more, three or more, five or more, seven or more, ten or more, fifteen or more, twenty or more, twenty-five or more, fifty or more, one hundred or more, two hundred and fifty or more, five hundred or more, one thousand or more, two thousand five hundred or more, five thousand or more, or ten thousand or more transducers. In some embodiments, the transducer array includes one hundred thousand or fewer, fifty thousand or fewer, twenty-five thousand or fewer, ten thousand or fewer, five thousand or fewer, two thousand five hundred or fewer, one thousand or fewer, five hundred or fewer, two hundred or fewer, one hundred and fifty or fewer, one hundred or fewer, ninety or fewer, eighty or fewer, seventy or fewer, sixty or fewer, fifty or fewer, forty or fewer, thirty or fewer, twenty-five or fewer, twenty or fewer, fifteen or fewer, ten or fewer, seven or fewer, five or fewer transducers. The transducer array can be, for example, a chip including fifty or more ultrasonic transducer pixels.

[0140] The interrogator shown in FIG. 12 shows a single transducer array, but the interrogator can include one or more, two or more, or three or more separate arrays. In some embodiments, the interrogator includes 10 or fewer transducer arrays (e.g., 9, 8, 7, 6, 5, 4, 3, 2, or 1 transducer array). The separate arrays can be arranged at different locations on the subject, for example, and can communicate with the same or different implantable devices. In some embodiments, the array is arranged on the opposite side of the implantable device. The interrogator can include an application specific integrated circuit (ASIC), and the application specific integrated circuit (ASIC) includes channels for each transducer within the transducer array. In some embodiments, the channel includes a switch (shown in FIG. 10 by "T / Rx"). The switch can alternatively configure the transducer connected to the channel to transmit or receive ultrasound. This switch can separate the ultrasound receiving circuit from the higher voltage ultrasound transmitting circuit.

[0141] In some embodiments, the transducer connected to the channel is configured only to receive ultrasonic waves or only to transmit ultrasonic waves, and the switch is optionally omitted from the channel. The channel can include a delay control unit that operates to control the transmitted ultrasonic waves. The delay control can control, for example, phase shift, time delay, pulse frequency, and / or waveform (including amplitude and wavelength). The delay control can be connected to a level shifter that shifts the input pulse to a higher voltage than that used by the transducer to transmit ultrasonic waves from the delay control. In some embodiments, data representing the waveform and frequency of each channel can be stored in a "wave table". Thereby, the transmission waveforms of each channel can be made different. Then, using the delay control and the level shifter, this data can be "streamed out" to the actual transmission signal to the transducer array. In some embodiments, the transmission waveform for each channel can be directly generated by the high-speed serial output of a microcontroller or other digital system and sent to the transducer element via a level shifter or a high-voltage amplifier. In some embodiments, the ASIC includes a charge pump (illustrated in FIG. 12) to convert a first voltage supplied to the ASIC to a second higher voltage applied to the channel. The channel can be controlled by a controller such as a digital controller that operates the delay control.

[0142] In the ultrasonic receiving circuit, the received ultrasonic wave is converted into current by a transducer (set to the receiving mode) and transmitted to the data capture circuit. In some embodiments, an amplifier, an analog-to-digital converter (ADC), a variable gain amplifier, or a time gain control variable gain amplifier that compensates for tissue loss, and / or a band-pass filter are included in the receiving circuit. The ASIC can draw power from a power source such as a battery (preferred for wearable embodiments of the interrogator). In the embodiment shown in FIG. 12, a 1.8V power supply is provided to the ASIC, which is increased to 32V by a charge pump, but any suitable voltage can be used. In one embodiment, the interrogator includes a processor and a non-transitory computer-readable memory. In some embodiments, the above-described channels do not include a T / Rx switch, and instead include independent Tx (transmission) and Rx (reception) with a high-voltage Rx (receiver circuit) in the form of a low-noise amplifier having good saturation recovery. In some embodiments, the T / Rx circuit includes a circulator. In some embodiments, the transducer array includes more transducer elements than the processing channels in the interrogator transmit / receive circuit, 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, where only 64 transducer elements are active on a given pulse.

[0143] In some embodiments, the interrogator is implantable. In some embodiments, the interrogator is external (i.e., not implanted). By way of example, an external interrogator can be wearable and can be secured to the body by a strap or adhesive. In another example, the external interrogator can be a wand that can be held by a user (such as a medical professional). In some embodiments, the interrogator can be held to the body via a clothing-based securing device such as a suture, simple surface tension, cloth wrap, sleeve, elastic band, or by subcutaneous fixation. The transducer or transducer array of the interrogator may be disposed separately from the remainder of the interrogator. For example, the transducer array can be secured to the skin of the subject at a first location (e.g., proximal to one or more implantable devices), the remainder of the interrogator can be disposed at a second location, and wires connect the transducer or transducer array to the remainder of the interrogator.

[0144] The specific design of the transducer array depends on the desired penetration depth, aperture size, and size of the individual transducers within the array. The Rayleigh distance R of the transducer array is calculated as follows: TIFF0007688024000001.tif2083where D is the size of the aperture and λ is the wavelength of the ultrasound within the propagation medium (i.e., tissue). As understood in the art, the Rayleigh distance is the distance at which the beam emitted by the array is fully formed. That is, the pressure field converges to a natural focus at the Rayleigh distance to maximize the received power. Thus, in some embodiments, the implantable device is at approximately the same distance from the transducer array as the Rayleigh distance.

[0145] Individual transducers within the transducer array can be modulated to control the Rayleigh distance and the position of the ultrasonic beam emitted by the transducer array through the process of beamforming or beam steering. Techniques such as linearly constrained minimum variance (LCMV) beamforming can be used to communicate multiple implantable devices with an external ultrasonic transceiver (transmitter / receiver). See, for example, Bertrand, et., al, Beamforming Approaches for Untethered, Ultrasonic Neural Dust Motes for Cortical Recording: a Simulation Study, IEEE EMBC (Aug. 2014). In some embodiments, beam steering is performed by adjusting the power or phase of the ultrasonic waves emitted by the transducers within the array.

[0146] In some embodiments, the interrogator includes one or more of an instruction to beam steer ultrasonic waves using one or more transducers, an instruction to determine the relative positions of one or more implantable devices, an instruction to monitor the relative movement of one or more implantable devices, an instruction to record the relative movement of one or more implantable devices, and an instruction to deconvolve backscattering from multiple implantable devices.

[0147] Optionally, the interrogator is controlled using a separate computer system such as a mobile terminal (e.g., a smartphone or tablet). The computer system can wirelessly communicate with the interrogator, for example, via a network connection, a radio frequency (RF) connection, or Bluetooth. The computer system can, for example, turn the interrogator on or off or analyze information encoded in the ultrasonic waves received by the interrogator.

[0148] <Communication between an Implantable Device and an Interrogator> The implantable device and the interrogator communicate wirelessly with each other, for example, using ultrasonic waves or radio frequencies. The communication may be one-way communication (for example, the interrogator transmits information to the implantable device, or the implantable device transmits information to the interrogator), or two-way communication (for example, the interrogator transmits information to the implantable device, or the implantable device transmits information to the interrogator). The information transmitted from the implantable device to the interrogator may depend on, for example, the backscatter communication protocol. For example, the interrogator can transmit ultrasonic or RF waves that emit backscatter waves encoding information to the implantable device. The interrogator can receive the backscatter waves and decode the information encoded in the received backscatter waves.

[0149] In some embodiments, an implantable device receives ultrasonic or radio frequency from an interrogator via one or more ultrasonic transducers or RF antennas on the implantable device, and the received wave can encode instructions for operating the implantable device. For example, the vibration of an ultrasonic transducer on the implantable device generates a voltage across the electrical terminals of the transducer, and current flows through a device including an integrated circuit. The current (which can be generated using, for example, one or more ultrasonic transducers or RF antennas) can be used to charge an energy storage circuit, which can store energy for use in emitting an electrical pulse, for example, after receiving a trigger signal. The trigger signal can be sent from the interrogator to the implantable device to signal that an electrical pulse should be emitted. In some embodiments, the trigger signal includes information regarding the electrical pulse to be emitted, such as frequency, amplitude, pulse length, or pulse shape (e.g., alternating current, direct current, or pulse pattern). A digital circuit can decode the trigger signal and operate the electrodes and electrical storage circuit to emit the pulse.

[0150] In some embodiments, an ultrasonic backscatterer or radio frequency backscatterer can be emitted from an implantable device and can encode information regarding the implantable device, an electrical pulse emitted by the implantable device, an electrophysiological pulse detected by the implantable device, or a detected physiological state. For example, the backscatterer can encode a verification signal that verifies that an electrical pulse has been emitted. In some embodiments, the implantable device is configured to detect an electrophysiological signal, and information regarding the detected electrophysiological signal can be transmitted to an interrogator by an ultrasonic backscatterer. To encode a signal in the backscatterer, a current flowing through an ultrasonic transducer of the implantable device is modulated as a function of the encoded information, such as the detected electrophysiological signal or the measured physiological state. In some embodiments, the modulation of the current can be an analog signal that can be directly modulated, for example, by the detected electrophysiological signal. In some embodiments, the modulation of the current encodes a digitized signal, which can be controlled by digital circuitry within an integrated circuit. The backscatterer is received by an external interrogator (which may be the same as or different from the external interrogator that initially transmitted the ultrasound). Thus, information from the electrophysiological signal can be encoded by changes in the amplitude, frequency, or phase of the backscattered ultrasound.

[0151] FIG. 13 shows an interrogator that communicates with an implantable device. An external ultrasonic transceiver emits ultrasonic waves (the “carrier wave”) that can pass through tissue. The carrier wave causes mechanical vibrations in an ultrasonic transducer (e.g., a bulk piezoelectric transducer, a PUMT, or a CMUT). A voltage is generated across the ultrasonic transducer, which in turn imparts a current flowing through an integrated circuit on the implantable device. The current flowing through the ultrasonic transducer causes the transducer on the implantable device to emit backscatter ultrasonic waves. In some embodiments, the integrated circuit modulates the current flowing through the ultrasonic transducer to encode information, and the resulting ultrasonic backscatter wave encodes the information. The backscatter wave can be detected by the interrogator and analyzed to interpret the information encoded in the ultrasonic backscatter.

[0152] Communication between an interrogator and an implantable device can use a pulse echo method that transmits and receives ultrasonic or RF waves. In the pulse echo method, the interrogator transmits a series of interrogation pulses at a predetermined frequency and then receives backscatter echoes from the implanted device. In some embodiments, the pulses are square, rectangular, triangular, sawtooth, or sinusoidal. In some embodiments, the output pulses 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 continuously transmitted by the interrogator during operation. In some embodiments when the pulses are continuously transmitted by the interrogator, some of the transducers on the interrogator are configured to receive ultrasonic waves and some of the transducers on the interrogator are configured to transmit ultrasonic waves. The transducer configured to receive ultrasonic waves and the transducer configured to transmit ultrasonic waves may be on the same transducer array or on different transducer arrays of the interrogator. In some embodiments, the transducers on the interrogator can be configured to alternatively transmit or receive ultrasonic waves. For example, the transducer can cycle between transmitting one or more pulses and a quiescent period. The transducer can be configured to transmit ultrasonic waves when transmitting one or more pulses and then can switch to a receive mode during the quiescent period.

[0153] In some embodiments, the backscattered waves are digitized by an implantable device. For example, the implantable device can include an oscilloscope or an analog-to-digital converter (ADC) and / or memory, which can digitally encode information in current (or impedance) variations. The digitized current variations can encode information and be received by a wireless communication system, which transmits the digitized ultrasound or radio frequency. The digitized data can compress analog data, for example, by using compression based on singular value decomposition (SVD) and least squares. In some embodiments, the compression is performed by a correlator or a pattern detection algorithm. The backscattered signal can undergo a series of non-linear transformations, such as fourth-order Butterworth bandpass filter rectified integration of the backscattered region, to generate a reconstructed data point at a single point in time. Such transformations can be performed either in hardware (i.e., hard-coded) or software.

[0154] In some embodiments, the digitized data can include a unique identifier. The unique identifier can be useful, for example, in a system comprising a plurality of implantable devices and / or an implantable device comprising a plurality of electrode pairs. For example, when the unique identifier is from a plurality of implantable devices, it can identify the originating implantable device, for example, when transmitting information (such as a verification signal) from the implantable device. In some embodiments, the implantable device includes a plurality of electrode pairs, which can emit electrical pulses simultaneously or alternatively by a single implantable device. For example, different pairs of electrodes can be configured to emit electrical pulses in different tissues (e.g., different nerves or different muscles) or different regions of the same tissue. The digitized circuitry can encode the unique identifier to identify and / or verify which electrode pair emitted the electrical pulse.

[0155] In some embodiments, the digitized signal compresses the size of the analog signal. By reducing the size of the digitized signal, more efficient reporting of the information encoded in the backscatter becomes possible. By compressing the size of the information transmitted by digitization, potentially overlapping signals can be accurately transmitted.

[0156] In some embodiments, an interrogator communicates with multiple implantable devices. This can be done, for example, using multiple-input multiple-output (MIMO) system theory. For example, time-division multiplexing, spatial multiplexing, or frequency multiplexing is used to communicate between the interrogator and the multiple implantable devices. The interrogator can perform inverse convolution (deconvolution) and receive the combined backscatter from the multiple implantable devices, thereby extracting information from each implantable device. In some embodiments, the interrogator focuses the ultrasonic waves transmitted from a transducer array to a specific implantable device via beam steering. The interrogator focuses the transmitted ultrasonic waves to a first implantable device, receives the backscatter from the first implantable device, focuses the transmitted ultrasonic waves to a second implantable device, and receives the backscatter from the second implantable device. In some embodiments, the interrogator transmits ultrasonic waves to multiple implantable devices and then receives the ultrasonic waves from the multiple implantable devices.

[0157] <Nerve Cuff and Method of Implanting a Device> A nerve cuff, or an implantable device including a nerve cuff, is implanted in a subject such that a helical nerve cuff at least partially wraps around fibrous tissue including a nerve where the electrodes of the device are in electrical communication with the nerve. The nerve cuff or the implantable device having the nerve cuff may be implanted in a surgical procedure using available surgical tools. Specific nerves or neurovascular bundles within a subject have limited space, and the implantation methods described herein may be beneficial for implanting a device or a helical nerve cuff within a small surgical field.

[0158] The implantable device or the helical nerve cuff may be implanted in a subject by at least partially unwinding the helical nerve cuff, passing an end of the helical nerve cuff behind the fibrous tissue including the nerve, and pulling the end of the helical nerve cuff that has passed behind the fibrous tissue. When the helical nerve cuff is partially unwound, the nerve cuff is in a bent state, the nerve cuff is released to a relaxed state, and the helical nerve cuff can wrap around the fibrous tissue. The helical nerve cuff may be arranged to be wound around the helical nerve cuff once, for example, by pulling the end of the helical nerve cuff under or behind the fibrous tissue.

[0159] The fibrous tissue may be isolated for implantation, for example, by circumferentially incising a part of the fibrous tissue or partially circumferentially incising to separate the fibrous tissue from the surrounding tissue. The initial incision can be made to access the fibrous tissue, which can be covered by other tissues. When the fibrous tissue is isolated, the implantable device or the helical nerve cuff may be brought into the surgical field. The helical nerve cuff or the implantable device may be oriented such that the axis of the helical nerve cuff is substantially parallel to the fibrous tissue. In this orientation, the end of the helical nerve cuff can pass behind (the back side of) the fibrous tissue (e.g., from under the fibrous tissue).

[0160] The end of the helical nerve cuff can first be passed behind the fibrous tissue by pressing against the end of the helical nerve cuff. A handle portion (e.g., a filament, suture, loop, etc.) can be attached to the end of the helical nerve cuff, which can be pulled to pass the helical nerve cuff behind the fibrous tissue.

[0161] In some embodiments, before pulling on the end of the helical nerve cuff that has passed behind the fibrous tissue, the helical nerve cuff is at least partially unwound. For example, the handle portion at one or both ends of the helical nerve cuff can be grasped and the helical nerve cuff manipulated to unwind the helix in a radial movement. When the helical nerve cuff is unwound, the nerve cuff assumes a bent configuration, the nerve cuff rebounds in a relaxed configuration, and the helix can be unwound. Then, the end of the at least partially unwound helix can pass behind the fibrous tissue (which can include pulling on the end of the helical nerve cuff). Once the end has passed through, the bent helical nerve cuff may be released, thereby securing the helical nerve cuff to wrap around the fibrous tissue. Next, the helical nerve cuff (and / or the body if present) can be repositioned to ensure contact between the electrodes of the helical nerve cuff and the fibrous tissue.

[0162] In some embodiments, the helical nerve cuff is at least partially unwound by pulling on the end of the helical nerve cuff that passes behind the fibrous tissue. For example, the end of the helical nerve cuff can be used to put the helical nerve cuff in a relaxed configuration (i.e., a bent helix) and pass it behind the fibrous tissue. Then, the end of the helical nerve cuff that has passed behind the fibrous tissue can be pulled (e.g., by pulling on the handle portion attached to the end of the helical nerve cuff). Pulling on the end of the helical nerve cuff causes the nerve cuff to be partially unwound as it passes behind the fibrous tissue. Next, the helical nerve cuff (and / or the body if present) can be repositioned to ensure contact between the electrodes of the helical nerve cuff and the fibrous tissue.

[0163] The body of the implantable device may be attached to the first end of the helical nerve cuff or to the center of the helical nerve cuff, and the second end of the helical nerve cuff is configured to pass behind the fibrous tissue. Optionally, when the end of the helical nerve cuff passes behind the fibrous tissue, the body can be held in a substantially stable position. For example, the implantable device may include a handle portion attached to the helical nerve cuff at a position proximal to the body or attached to the body itself, and this handle portion may be gripped to stabilize the body. There may be some slight movement of the body, but the movement of the body can be restricted to avoid the body being caught on the surrounding tissue or fibrous tissue when the helical nerve cuff passes behind the fibrous tissue. When the helical nerve cuff of the implantable device is wrapped around the fibrous tissue, the body of the implantable device may be arranged in a desired orientation.

[0164] When the helical nerve cuff of the implantable device is wrapped around the fibrous tissue, the body of the implantable device may be arranged in a desired orientation. For example, if the body includes an acoustic window, the acoustic window of the body can be directed towards the direction of the desired interrogator position.

[0165] The implantable device is implanted in a mammalian subject. In some embodiments, the subject is a human, dog, cat, horse, cow, pig, sheep, goat, monkey, or rodent (such as a rat or mouse). The helical nerve cuff may be implanted so as to at least partially wrap around a fibrous tissue (peripheral nerve or fibrous tissue including a peripheral nerve, e.g., a neurovascular bundle) within any of these animals or other animals. For example, in some embodiments, the helical nerve cuff or implantable device is implanted such that the nerve cuff at least partially wraps around a human peripheral nerve such as the human splenic nerve or the human splenic neurovascular bundle. In some embodiments, the helical nerve cuff or implantable device is implanted such that the nerve cuff at least partially wraps around an autonomic nerve. In some embodiments, the nerve is a sympathetic nerve. 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.

[0166] Figure 14 is a flowchart showing a method of implanting a helical nerve cuff in a subject. In step 1402, the helical nerve cuff is at least partially unwound, which configures the helical nerve cuff in a bent configuration. In step 1404, the ends of the helical nerve cuff pass behind the fibrous tissue containing the nerve. The fibrous tissue may be, for example, a neurovascular bundle such as the splenic nerve and the splenic artery. The ends of the helical nerve cuff may be pushed under the fibrous tissue, which exposes the handle portion on the opposite side of the fibrous tissue. Optionally, the handle portion may be pulled to pass the helical nerve cuff behind the fibrous tissue. In step 1406, the helical nerve cuff is wrapped around the fibrous tissue. When released from the bent configuration of the helical nerve cuff, the nerve cuff can snap back to a relaxed configuration, whereby the helical nerve cuff can wrap around the fibrous tissue. Optionally, the helical nerve cuff may be repositioned (e.g., by pulling on one or more handle portions) to ensure that one or more electrodes of the helical nerve cuff contact the fibrous tissue.

[0167] FIG. 15 is a flowchart showing another method of implanting a helical nerve cuff in a subject. At step 1502, the end of the helical nerve cuff passes behind the fibrous tissue containing the nerve. The fibrous tissue may be, for example, a neurovascular bundle such as the splenic nerve and splenic artery. The end of the helical nerve cuff can be pushed under the fibrous tissue, which exposes the handle portion on the opposite side of the fibrous tissue. At step 1504, the end of the helical nerve cuff is pulled (e.g., manipulated) to pass the helical nerve cuff behind the fibrous tissue, whereby the helical nerve cuff is at least partially wound back. At step 1506, the helical nerve cuff is wrapped around the fibrous tissue. When released from the bent configuration of the helical nerve cuff, the nerve cuff can rebound to a relaxed configuration, whereby the helical nerve cuff can wrap around the fibrous tissue. Optionally, the helical nerve cuff may be repositioned (e.g., by pulling on one or more handle portions) to ensure that one or more electrodes of the helical nerve cuff contact the fibrous tissue.

[0168] FIG. 16 is a flowchart showing a method of implanting an implantable device including a helical nerve cuff into a subject. The body of the implantable device is attached to a first end of the helical nerve cuff. In step 1602, the helical nerve cuff of the implantable device is at least partially unwound to configure the helical nerve cuff in a bent configuration. In step 1604, a second end of the helical nerve cuff passes behind a fibrous tissue containing nerves. The fibrous tissue may be, for example, a neurovascular bundle such as the splenic nerve and the splenic artery. The second end of the helical nerve cuff can be pushed under the fibrous tissue, which exposes a handle portion on the opposite side of the fibrous tissue. Optionally, the helical nerve cuff can be passed behind the fibrous tissue by pulling on a handle portion attached to the helical nerve cuff proximal to the second end. In step 1606, the helical nerve cuff is wrapped around the fibrous tissue. When released from the bent configuration, the nerve cuff can rebound to a relaxed configuration, whereby the helical nerve cuff can wrap around the fibrous tissue. Optionally, the helical nerve cuff and / or the body of the implantable device can be repositioned (e.g., by pulling on one or more handle portions) to ensure that one or more electrodes of the helical nerve cuff contact the fibrous tissue.

[0169] FIG. 17 is a flowchart showing another method of implanting an implantable device including a helical nerve cuff into a subject. The body of the implantable device is attached to the first end of the helical nerve cuff. At step 1702, the second end of the helical nerve cuff passes behind the fibrous tissue containing the nerve. The fibrous tissue may be, for example, a neurovascular bundle such as the splenic nerve and the splenic artery. The end of the helical nerve cuff can be pushed under the fibrous tissue, which exposes the handle portion on the opposite side of the fibrous tissue. At step 1704, the second end of the helical nerve cuff is pulled (e.g., by a handle), passing the helical nerve cuff behind the fibrous tissue, whereby the helical nerve cuff is at least partially wound back. At step 1706, the helical nerve cuff is wound around the fibrous tissue. When released from the bent configuration of the helical nerve cuff, the nerve cuff can rebound to a relaxed configuration, whereby the helical nerve cuff can wrap around the fibrous tissue. Optionally, the helical nerve cuff may be repositioned (e.g., by pulling on one or more handle portions) to ensure that one or more electrodes of the helical nerve cuff contact the fibrous tissue.

[0170] <Method for manufacturing an implantable device> The implantable device can be fabricated by attaching the device body to the helical nerve cuff or by assembling the helical nerve cuff on the device body. For example, the helical nerve cuff may include two or more substrate layers, and the first substrate layer may be attached to the device body before the second substrate layer is attached to the first substrate layer, thus forming the helical nerve cuff.

[0171] FIG. 18 shows a flowchart of an exemplary method of fabricating an implantable device. The steps of the method are described in an exemplary order, but it is understood that the order of the steps can be changed as would be understood by one of ordinary skill in the art.

[0172] In step 1802, the feedthrough is attached to the housing. The housing can include a feedthrough port configured to receive the feedthrough, for example, at the bottom of the housing. The feedthrough can then be attached to the housing at the feedthrough port, for example, by welding or brazing the feedthrough to the housing. By attaching the feedthrough to the feedthrough port of the housing, a seal can be provided at the feedthrough port.

[0173] In step 1804, the board assembly is disposed within the housing. The board assembly can include a wireless communication system (e.g., one or more ultrasonic transducers), an integrated circuit, and / or other electronic components of the body. One or more of these components can be attached to the flexible board, for example, by using a conductive adhesive and / or by wire bonding the components to form the board assembly. The board assembly is disposed within the housing to electrically connect the feedthrough to the board assembly. Alternatively, the feedthrough can be attached to the board assembly before the board assembly is positioned within the housing, and then, when the board assembly is disposed in a predetermined position, the feedthrough can be attached to the housing.

[0174] In step 1806, the opening portion of the housing is closed with a lid, such as an acoustic window, for example. The board assembly can be positioned within the housing, for example, through the opening. The lid can include an acoustic window. For example, if the wireless communication system of the board assembly includes one or more ultrasonic transducers, the acoustic window can be included so that ultrasonic waves can pass through the housing. The acoustic window can be formed, for example, by attaching a foil to a frame (e.g., by nucleic acid bonding the foil to the frame). The acoustic window can then be attached to the housing opening, for example, by laser welding.

[0175] In step 1808, the housing is filled with an acoustically conductive material. This step is optional and may not be applied, for example, if the wireless communication system is not an acoustic-based communication system. However, if the wireless communication system includes one or more ultrasonic transducers, filling the housing with an acoustically conductive material can enable better communication using ultrasonic waves. The acoustically conductive material may be filled into the housing using a port, which may be included on the side of the housing. Optionally, a vacuum can be used to ensure that there are no air bubbles in the acoustically conductive material. Once the housing is filled, the port can be sealed, for example, by placing a plug into the port, and this plug can be soldered or laser welded to seal the plug in place.

[0176] Once assembled, the housing is preferably sealed (e.g., by sealing any housing openings such as the open housing top, feed-through ports, and / or the acoustically conductive material port).

[0177] In step 1810, a first substrate layer for the nerve cuff is formed. The first nerve cuff layer may be shaped or cut into a helical shape. The feed-through port may also be cut or shaped into the first nerve cuff layer configured to allow a feed-through attached to the housing to pass through the feed-through port of the first layer.

[0178] In step 1812, the first substrate layer (i.e., the outer layer) is attached to the housing. The housing is aligned with the first substrate layer such that the feed-throughs attached to the housing pass through the feed-through ports of the first substrate layer. The housing may be positioned as desired relative to the helical axis, such as parallel or perpendicular to the helical axis. An adhesive and / or one or more fasteners may be used to fix the housing to the first substrate layer. For example, the housing may have one or more attached fasteners (e.g., soldered, welded, formed to form the housing), which can be operated to pass through the first substrate and fix the housing to the first layer.

[0179] In step 1814, a second substrate layer (e.g., the inner layer) is formed. One or more electrodes may be shaped (e.g., by laser cutting a conductive material) and then embedded within the second substrate material. If necessary, flashing can be removed from the second substrate material to ensure the desired exposure.

[0180] In step 1816, a second substrate layer is attached to the first substrate layer. The second substrate layer may be aligned with the first substrate layer in order to align the feedthroughs with the electrodes, whereby the electrodes are electrically connected to the board assembly through the feedthroughs. The electrodes can be attached to the feedthroughs, for example, by soldering the feedthroughs to the electrodes and / or by using an adhesive. Then, an adhesive can be used to attach the second substrate layer to the first substrate layer, thereby forming a helical nerve cuff. Optionally, the second substrate layer is wrapped around a shaft body (mandrel), the first substrate layer is wrapped around the second substrate layer, while the second substrate layer is wrapped around the mandrel. In some embodiments, one or more handle portions are attached to the device, for example, by attaching one or more handle portions to the housing, the first substrate layer, the second substrate layer, or between the first substrate layer and the second substrate layer when the first substrate layer is attached to the second substrate layer.

[0181] <Exemplary Embodiment> The following embodiments are exemplary and are not intended to limit the scope of the present application:

[0182] (Example 1) An implantable device, a body including a wireless communication system, two or more electrodes configured to detect electrophysiological signals transmitted by nerves or to emit electrical pulses to nerves and electrically communicate with the wireless communication system, a helical nerve cuff comprising at least one of the two or more electrodes, the body being on the helical nerve cuff, the helical nerve cuff at least partially wound around a fibrous tissue having a nerve, and configured to electrically connect at least one of the two or more electrodes to the nerve, An implantable device comprising.

[0183] (Example 2) The wireless communication system is the implantable device according to Example 1, comprising an ultrasonic transducer.

[0184] (Example 3) The ultrasonic transducer is the implantable device according to Example 2, having a length of about 5 mm or less in the longest dimension.

[0185] (Example 4) The wireless communication system is the implantable device according to Example 2 or 3, comprising two or more ultrasonic transducers.

[0186] (Example 5) The wireless communication system is the implantable device according to Example 1, comprising a radio frequency antenna.

[0187] (Example 6) The wireless communication system is configured to receive ultrasonic or radio frequency waves and convert the energy from the ultrasonic or radio frequency waves into electrical energy for powering the device, and is the implantable device according to any one of Examples 1 to 5.

[0188] (Example 7) The helical nerve cuff is configured to wrap around the nerve at least once, and is the implantable device according to any one of Examples 1 to 6.

[0189] (Example 8) The helical nerve cuff is configured to wrap around the nerve about 1.3 to about 1.7 times, and is the implantable device according to Example 7.

[0190] (Example 9) The helical nerve cuff has a width defining an inner surface, a first edge, and a second edge of the helical nerve cuff, and at least a part of the first edge contacts at least a part of the second edge when the helical nerve cuff is in a relaxed position, and is the implantable device according to any one of Examples 1 to 8.

[0191] (Example 10) An implantable device according to any one of Examples 1 to 8, wherein the helical nerve cuff has a width defining an inner surface, a first edge, and a second edge of the helical nerve cuff, and the first edge does not contact the second edge when the helical nerve cuff is in a relaxed position.

[0192] (Example 11) An implantable device according to any one of Examples 1 to 10, wherein at least one of the two or more electrodes is arranged along the length of the helical nerve cuff.

[0193] (Example 12) An implantable device according to Example 11, wherein at least one of the two or more electrodes arranged along the length of the helical nerve cuff is arranged on the inner surface of the helical nerve cuff.

[0194] (Example 13) An implantable device according to any one of Examples 1 to 12, wherein at least one electrode on the helical nerve cuff includes one or more serpentine segments.

[0195] (Example 14) An implantable device according to any one of Examples 1 to 13, wherein the helical nerve cuff is flexible and configurable between (a) a bent position by at least partially winding back the helical nerve cuff and (b) a relaxed position.

[0196] (Example 15) An implantable device according to any one of Examples 1 to 14, further comprising a handle portion attached to the helical nerve cuff or the body.

[0197] (Example 16) An implantable device according to Example 15, wherein the handle portion includes a loop.

[0198] (Example 17) An implantable device according to Example 15 or 16, wherein the handle portion includes a filament.

[0199] (Example 18) The handle part is an implantable device according to any one of Examples 15 to 17, which is attached to the nerve cuff at a position proximal to the end of the helical nerve cuff.

[0200] (Example 19) The implantable device according to Example 18, further comprising a second handle part attached to the helical nerve cuff at a position proximal to the second end of the helical nerve cuff.

[0201] (Example 20) The implantable device according to Example 19, wherein the first handle part is attached to the second handle.

[0202] (Example 21) The implantable device according to any one of Examples 16 to 20, further comprising an additional handle part attached at an intermediate position along the length of the helical nerve cuff.

[0203] (Example 22) The implantable device according to any one of Examples 1 to 21, further comprising a mount configured to receive the body and the helical nerve cuff, thereby attaching the body to the helical nerve cuff.

[0204] (Example 23) The implantable device according to any one of Examples 1 to 21, wherein the body is directly attached to the outer surface of the helical nerve cuff.

[0205] (Example 24) The implantable device according to any one of Examples 1 to 23, wherein the body is attached to the end of the helical nerve cuff.

[0206] (Example 25) The implantable device according to any one of Examples 1 to 23, wherein the body is attached to the central portion of the helical nerve cuff.

[0207] (Example 26) The implantable device according to any one of Examples 1 to 25, wherein the main body includes an attachment end portion attached to the helical nerve cuff and an extension end portion extending from the attachment end portion.

[0208] (Example 27) The implantable device according to any one of Examples 1 to 26, wherein the helical nerve cuff includes a right-handed helical portion.

[0209] (Example 28) The implantable device according to any one of Examples 1 to 26, wherein the helical nerve cuff includes a left-handed helical portion.

[0210] (Example 29) The implantable device according to any one of Examples 1 to 28, wherein the helical nerve cuff includes a right-handed helical portion joined to the left-handed helical portion.

[0211] (Example 30) The implantable device according to Example 29, wherein the main body is attached to the helical nerve cuff at a position proximal to the position where the right-handed helical portion is joined to the left-handed helical portion.

[0212] (Example 31) The implantable device according to Example 29 or 30, wherein the right-handed helical portion is joined to the left-handed helical portion via a linear joint portion.

[0213] (Example 32) The implantable device according to any one of Examples 1 to 31, wherein the helical nerve cuff includes one or more electrodes configured to emit an electrical pulse to the nerve.

[0214] (Example 33) The implantable device according to any one of Examples 1 to 32, wherein the helical nerve cuff includes one or more electrodes configured to detect an electrophysiological signal transmitted by the nerve.

[0215] (Example 34) The helical nerve cuff is an implantable device according to Example 33, comprising two or more electrodes configured to detect electrophysiological signals transmitted by a nerve.

[0216] (Example 35A) The implantable device according to any one of Examples 1 to 34, wherein the nerve is the human splenic nerve.

[0217] (Example 35B) The implantable device according to any one of Examples 1 to 34, wherein the nerve is the human visceral nerve.

[0218] (Example 36) The implantable device according to any one of Examples 1 to 35A and 35B, wherein the body includes a housing.

[0219] (Example 37) The implantable device according to Example 36, wherein the housing is configured as one of the two or more electrodes.

[0220] (Example 38) The implantable device according to Example 36 or 37, wherein the housing includes an acoustic window.

[0221] (Example 39) The implantable device according to any one of Examples 36 to 38, wherein the housing includes an acoustically conductive material.

[0222] (Example 40) The implantable device according to any one of Examples 1 to 39, wherein the body includes a wireless communication system and an integrated circuit electrically connected to the two or more electrodes.

[0223] (Example 41) The implantable device according to Example 40, wherein the integrated circuit includes an energy storage circuit including a capacitor.

[0224] (Example 42) The implantable device according to any one of Examples 1 to 41, wherein the length in the longest dimension is about 8 mm or less.

[0225] (Example 43) The implantable device according to any one of Examples 1 to 42, which is configured to transmit data.

[0226] (Example 44) The implantable device according to Example 43, which is configured to emit an ultrasonic backscatterer or a radio frequency backscatterer that encodes the data.

[0227] (Example 45) The implantable device according to Example 43 or 44, wherein the data includes information related to a detected electrophysiological signal, a measured physiological state, a device state, or an emitted electrical pulse.

[0228] (Example 46) The implantable device according to any one of Examples 1 to 45, which is configured to receive an instruction for operating the implantable device.

[0229] (Example 47) The implantable device according to Example 46, wherein the instruction is encoded by ultrasonic waves or radio frequencies.

[0230] (Example 48) The implantable device according to Example 46 or 47, wherein the instruction includes a trigger signal for operating the implantable device to emit an electrical pulse to a nerve.

[0231] (Example 49) The implantable device according to any one of Examples 1 to 48, further comprising a sensor configured to detect a physiological state.

[0232] (Example 50) The implantable device according to Example 49, wherein the sensor is configured to detect temperature, pH, pressure, strain, or analyte concentration.

[0233] (Example 51) An implantable device according to any one of Examples 1 to 50, wherein the fibrous tissue includes blood vessels.

[0234] (Example 52) A system comprising an implantable device according to any one of Examples 1 to 51 and an interrogator configured to wirelessly communicate with a wireless communication system of the implantable device and a second wireless communication system.

[0235] (Example 53) The system according to Example 52, wherein the second wireless communication system includes one or more ultrasonic transducers configured to transmit ultrasonic waves to the implantable medical device, and the ultrasonic waves supply power to the implantable medical device.

[0236] (Example 54) The system according to Example 52, wherein the second wireless communication system includes one or more radio frequency antennas configured to transmit radio frequencies to the implantable medical device, and the radio frequencies supply power to the implantable medical device.

[0237] (Example 55) The system according to any one of Examples 52 to 54, wherein the interrogator is configured to be worn externally.

[0238] (Example 56) A nerve cuff, a flexible helical substrate configured to at least partially wrap around fibrous tissue including a nerve, the flexible helical substrate being configurable to (a) a bent position by at least partially rewinding the helical nerve cuff and (b) a relaxed position, one or more electrodes disposed along the length of the helical substrate, a handle portion attached to the helical substrate and configured to apply a force to configure the helical substrate in the bent position, and including the nerve cuff.

[0239] (Example 57) The nerve cuff according to Example 56, wherein the handle portion includes a loop.

[0240] (Example 58) The nerve cuff according to Example 56 or 57, wherein the handle portion contains a filament.

[0241] (Example 59) The nerve cuff according to any one of Examples 56 to 58, wherein the helical nerve cuff is configured to wrap around the nerve at least once.

[0242] (Example 60) The nerve cuff according to Example 59, wherein the helical nerve cuff is configured to wrap around the nerve about 1.3 to about 1.7 turns.

[0243] (Example 61) The nerve cuff according to any one of Examples 56 to 60, wherein a part of the handle portion is embedded in the substrate.

[0244] (Example 62) The nerve cuff according to any one of Examples 56 to 61, wherein the handle portion is attached to the nerve cuff at a position proximal to the end of the helical nerve cuff.

[0245] (Example 63) The nerve cuff according to Example 62, further comprising a second handle portion attached to the helical nerve cuff at a position proximal to the second end of the helical nerve cuff.

[0246] (Example 64) The nerve cuff according to Example 63, wherein the first handle portion and the second handle portion are separated by a radial angle of about 90° to about 180° around the helical axis.

[0247] (Example 65) The nerve cuff according to Example 63 or 64, wherein the first handle portion is attached to the second handle portion.

[0248] (Example 66) The implantable device according to any one of Examples 56 to 65, further comprising an additional handle portion attached at an intermediate position along the length of the helical nerve cuff.

[0249] (Example 67) The nerve cuff according to any one of Examples 56 to 66, wherein the substrate has a width defining an inner surface, a first edge of the substrate, and a second edge of the substrate, and at least a part of the first edge contacts at least a part of the second edge when the nerve cuff is in the relaxed position.

[0250] (Example 68) The nerve cuff according to any one of Examples 56 to 66, wherein the substrate has a width defining an inner surface, a first edge of the substrate, and a second edge of the substrate, and the first edge does not contact the second edge when the nerve cuff is in the relaxed position.

[0251] (Example 69) The nerve cuff according to any one of Examples 56 to 68, wherein at least one of the one or more electrodes is arranged along the length of the helical nerve cuff.

[0252] (Example 70) The nerve cuff according to Example 69, wherein at least one of the one or more electrodes arranged along the length of the helical nerve cuff is arranged on the inner surface of the helical nerve cuff.

[0253] (Example 71) The nerve cuff according to any one of Examples 56 to 70, wherein at least one of the one or more electrodes includes one or more meandering segments.

[0254] (Example 72) The nerve cuff according to any one of Examples 56 to 71, wherein the helical nerve cuff is configured to be wound back at least once.

[0255] (Example 73) The nerve cuff according to any one of Examples 56 to 72, wherein the helical nerve cuff includes a right-handed helical portion.

[0256] (Example 74) The nerve cuff according to any one of Examples 56 to 72, wherein the helical nerve cuff includes a left-handed helical portion.

[0257] (Example 75) The nerve cuff according to any one of Examples 56 to 73, wherein the helical nerve cuff includes a right-handed helical portion joined to a left-handed helical portion.

[0258] (Example 76) The nerve cuff according to any one of Examples 56 to 75, comprising a first helical portion joined to a second helical portion via a linear connecting member.

[0259] (Example 77) The nerve cuff according to any one of Examples 56 to 76, comprising one or more electrodes configured to emit an electrical pulse to a nerve.

[0260] (Example 78) The nerve cuff according to any one of Examples 56 to 77, comprising one or more electrodes configured to detect the electrophysiological signal transmitted by a nerve.

[0261] (Example 79) The nerve cuff according to Example 78, comprising two or more electrodes configured to detect the electrophysiological signal transmitted by a nerve.

[0262] (Example 80) The nerve cuff according to any one of Examples 56 to 79, comprising one or more electrodes configured to detect the electrophysiological signal transmitted by a nerve and one or more electrodes configured to emit an electrical pulse to a nerve, wherein at least one of the one or more electrodes configured to emit an electrical pulse to a nerve is wider than at least one of the one or more electrodes configured to detect the electrophysiological signal transmitted by a nerve.

[0263] (Example 81) The nerve cuff according to any one of Examples 56 to 80, further comprising a mount attached to a helical substrate configured to receive a body and electrically connect one or more electrodes disposed along the length of the helical substrate to the body.

[0264] (Example 82) The nerve cuff according to Example 81, wherein the body is directly connected to one or more electrodes.

[0265] (Example 83) The nerve cuff according to Example 81, wherein the mount includes one or more feedthroughs configured to electrically connect the body to one or more electrodes.

[0266] (Example 84A) The nerve cuff according to any one of Examples 56 to 83, wherein the nerve is the splenic nerve.

[0267] (Example 84B) The nerve cuff according to any one of Examples 56 to 83, wherein the nerve is the splanchnic nerve.

[0268] (Example 85) A method of implanting a helical nerve cuff including one or more electrodes, comprising: at least partially unwinding the helical nerve cuff; passing an end of the helical nerve cuff behind fibrous tissue including the nerve; wrapping the helical nerve cuff around the fibrous tissue. A method comprising the above.

[0269] (Example 86) The method according to Example 85, wherein the helical nerve cuff is the nerve cuff according to any one of Examples 56 to 85.

[0270] (Example 87) A method of implanting an implantable device comprising a body with a wireless communication system into a helical nerve cuff having one or more electrodes, comprising: at least partially unwinding the nerve cuff; passing an end of the helical nerve cuff behind fibrous tissue including the nerve; wrapping the helical nerve cuff around the fibrous tissue. A method comprising the above.

[0271] (Example 88) The method according to Example 87, comprising restricting movement of the body when an end of the helical nerve cuff passes behind the fibrous tissue.

[0272] (Example 89) The method according to Example 88, wherein the body is held in a substantially stable position by holding it in a handle portion attached to the helical nerve cuff at a position proximal to the body or in a handle portion attached to the body.

[0273] (Example 90) The method according to any one of Examples 87 to 89, wherein the implantable device is the implantable device according to any one of Examples 1 to 51.

[0274] (Example 91) The method according to any one of Examples 85 to 90, comprising pulling an end portion of the helical nerve cuff through the rear of the fibrous tissue.

[0275] (Example 92) The method according to any one of Examples 85 to 91, comprising orienting the helical nerve cuff substantially parallel to the fibrous tissue.

[0276] (Example 93) The method according to any one of Examples 85 to 92, wherein the helical nerve cuff is at least partially wound back by pulling an end portion of the helical nerve cuff through the rear of the fibrous tissue.

[0277] (Example 94) The method according to any one of Examples 85 to 92, wherein the helical nerve cuff is at least partially wound back before pulling an end portion of the helical nerve cuff through the rear of the fibrous tissue.

[0278] (Example 95) The method according to any one of Examples 85 to 94, wherein the end portion of the helical nerve cuff passes from below the fibrous tissue through the rear of the fibrous tissue.

[0279] (Example 96) The method according to any one of Examples 85 to 95, further comprising separating the fibrous tissue from the surrounding tissue.

[0280] (Example 97) The method according to Example 96, wherein the fibrous tissue is separated from the surrounding tissue by circumferentially incising a part of the fibrous tissue.

[0281] (Example 98) The method according to any one of Examples 85 to 97, wherein the end of the helical nerve cuff passing through the fibrous tissue is pulled by pulling a handle portion attached to the end of the helical nerve cuff.

[0282] (Example 99A) The method according to any one of Examples 85 to 98, wherein the fibrous tissue includes the splenic nerve.

[0283] (Example 99B) The method according to any one of Examples 85 to 98, wherein the fibrous tissue includes the splanchnic nerve.

[0284] (Example 100) A method for manufacturing an implantable device, comprising: attaching a feedthrough to a housing; positioning a board assembly including a wireless communication system within the housing; attaching the housing to a first nerve cuff layer; attaching the first nerve cuff layer to a second nerve cuff layer including one or more electrodes; electrically connecting one or more electrodes of the nerve cuff to the board assembly via the feedthrough; and.

[0285] (Example 101) The method according to Example 100, wherein the feedthrough is attached to the housing before the board assembly is disposed within the housing.

[0286] (Example 102) The method according to Example 100, wherein the feedthrough is attached to the board assembly before the board assembly is disposed within the housing.

[0287] (Example 103) The method according to any one of Examples 100 to 102, including sealing the housing.

[0288] (Example 104) The method according to any one of Examples 100 to 103, including attaching an acoustic window to a housing.

[0289] (Example 105) The method according to Example 104, wherein the acoustic window is attached to the open top of the housing after the board assembly is disposed within the housing.

[0290] (Example 106) The method according to Example 104 or 105, including assembling the acoustic window by attaching a foil to a frame.

[0291] (Example 107) The method according to any one of Examples 100 to 106, including filling the housing with an acoustically conductive material.

[0292] (Example 108) The method according to Example 107, wherein the acoustically conductive material is filled into the housing through a port on the housing, and the method includes sealing the port.

[0293] (Example 109) The method according to any one of Examples 100 to 108, including attaching a wireless communication system to the board assembly.

[0294] (Example 110) The method according to any one of Examples 100 to 109, wherein the wireless communication system includes one or more ultrasonic transducers.

[0295] (Example 111) The method according to any one of Examples 100 to 110, wherein the board assembly includes an integrated circuit electrically connected to the wireless communication system.

[0296] (Example 112) The method according to any one of Examples 100 to 111, wherein the housing is directly attached to a first nerve cuff layer.

[0297] (Example 113) The method according to any one of Examples 100 to 112, wherein an adhesive or a fixture is used to attach the housing to the first nerve cuff layer.

[0298] (Example 114) The method according to any one of Examples 100 to 113, wherein the first nerve cuff layer is helical.

[0299] (Example 115) The method according to any one of Examples 100 to 114, including attaching one or more handle portions between the body, the first nerve cuff layer, the second nerve cuff layer, or between the first nerve cuff layer and the second nerve cuff layer.

[0300] (Example 116) The method according to any one of Examples 100 to 115, including fabricating the second nerve cuff layer by embedding one or more electrodes in a substrate material.

[0301] (Example 117) The method according to any one of Examples 100 to 116, including winding the second nerve cuff layer around the shaft body and attaching the second nerve cuff layer to the first nerve cuff layer while the second nerve cuff layer is wound around the shaft body.

Claims

1. An implantable device, a main body including a wireless communication system, two or more electrodes configured to detect electrophysiological signals transmitted by nerves or to emit electrical pulses to the nerves, and electrically communicating with the wireless communication system, a helical nerve cuff including at least one of the two or more electrodes, the helical nerve cuff being configured to at least partially wrap around a fibrous tissue having the nerve and to dispose at least one of the two or more electrodes to be electrically connected to the nerve, a handle portion attached to the helical nerve cuff, and an implantable device comprising the same.

2. The implantable device according to claim 1, wherein the wireless communication system comprises one or more ultrasonic transducers.

3. The implantable device according to claim 2, wherein the ultrasonic transducer has a length of 5 mm or less in the longest dimension.

4. The implantable device according to claim 1, wherein the wireless communication system comprises a radio frequency antenna.

5. The implantable device according to any one of claims 1 to 4, wherein the wireless communication system is configured to receive ultrasonic waves or radio frequencies and convert the energy from the ultrasonic waves or radio frequencies into electrical energy for powering the implantable device.

6. The implantable device according to any one of claims 1 to 5, wherein the helical nerve cuff is configured to wrap around the nerve at least once.

7. The implantable device according to claim 6, wherein the helical nerve cuff is configured to wrap around the nerve 1.3 to 1.7 times.

8. The implantable device according to any one of claims 1 to 7, wherein the helical nerve cuff has a width defining an inner surface, a first edge, and a second edge of the helical nerve cuff, and when the helical nerve cuff is in a relaxed position, at least a part of the first edge contacts at least a part of the second edge.

9. The helical nerve cuff has a width defining an inner surface, a first edge, and a second edge of the helical nerve cuff, and when the helical nerve cuff is in a relaxed position, the first edge does not contact the second edge, the implantable device according to any one of claims 1 to 7.

10. The implantable device according to any one of claims 1 to 9, wherein at least one of the two or more electrodes is arranged along a length along the helix of the helical nerve cuff.

11. The implantable device according to claim 10, wherein at least one of the two or more electrodes arranged along the length along the helix of the helical nerve cuff is arranged on an inner surface of the helical nerve cuff.

12. The implantable device according to any one of claims 1 to 11, wherein at least one of the two or more electrodes on the helical nerve cuff includes one or more meandering segments.

13. The helical nerve cuff is flexible and configurable to (a) a bent position by at least partially unwinding the helical nerve cuff and (b) a relaxed position, the implantable device according to any one of claims 1 to 12.

14. The implantable device according to any one of claims 1 to 13, wherein the handle portion includes a loop.

15. The implantable device according to any one of claims 1 to 14, wherein the handle portion includes a filament.

16. The implantable device according to any one of claims 1 to 15, wherein the handle portion is attached to the helical nerve cuff at an end of the helical nerve cuff.

17. The implantable device according to any one of claims 1 to 16, further comprising a second handle portion attached to the helical nerve cuff at a second end of the helical nerve cuff.

18. The implantable device according to claim 17, wherein the handle portion is attached to the second handle portion.

19. The implantable device according to any one of claims 1 to 18, further comprising an additional handle portion attached at an intermediate position along a length along the helix of the helical nerve cuff.

20. The implantable device according to any one of claims 1 to 19, further comprising a mount configured to receive the body and the helical nerve cuff and thereby attach the body to the helical nerve cuff.

21. The implantable device according to any one of claims 1 to 19, wherein the body is directly attached to an outer surface of the helical nerve cuff.

22. The implantable device according to any one of claims 1 to 21, wherein the body is attached to an end portion of the helical nerve cuff or an intermediate position of the helical nerve cuff.

23. The implantable device according to any one of claims 1 to 22, wherein the body includes an attachment end portion attached to the helical nerve cuff and an extension end portion extending from the attachment end portion.

24. The implantable device according to any one of claims 1 to 23, wherein the helical nerve cuff includes a right-handed spiral portion or a left-handed spiral portion.

25. The implantable device according to any one of claims 1 to 24, wherein the helical nerve cuff includes a right-handed spiral portion joined to a left-handed spiral portion.

26. The implantable device according to claim 25, wherein the body is attached to the helical nerve cuff at a position where the right-handed spiral portion is joined to the left-handed spiral portion.

27. The implantable device according to claim 25 or 26, wherein the right-handed spiral portion is joined to the left-handed spiral portion via a linear joint portion.

28. The implantable device according to any one of claims 1 to 27, wherein the nerve is a human splenic nerve.

29. The implantable device according to any one of claims 1 to 28, wherein the body includes a housing.

30. The implantable device according to claim 29, wherein the housing is configured as one of the two or more electrodes.

31. The implantable device according to claim 29 or 30, wherein the housing includes an acoustic window.

32. The implantable device according to any one of claims 29 to 31, wherein the housing includes an acoustically conductive material.

33. The implantable device according to any one of claims 1 to 32, wherein the body includes an integrated circuit electrically connected to the wireless communication system and the two or more electrodes.

34. The implantable device according to claim 33, wherein the integrated circuit includes an energy storage circuit including a capacitor.

35. The implantable device according to any one of claims 1 to 34, wherein the length of the body in the longest dimension is 8 mm or less.

36. The implantable device according to any one of claims 1 to 35, wherein the wireless communication system is configured to transmit data.

37. The implantable device according to claim 36, wherein the wireless communication system is configured to emit an ultrasonic backscatterer or a radio frequency backscatterer that encodes the data.

38. The implantable device according to claim 36 or 37, wherein the data includes information related to a detected electrophysiological signal, a measured physiological state, a device state, or an emitted electrical pulse.

39. The implantable device according to any one of claims 1 to 38, wherein the wireless communication system is configured to receive an instruction for operating the implantable device.

40. The implantable device according to claim 39, wherein the instruction is encoded by ultrasonic waves or radio frequencies.

41. The implantable device according to claim 39 or 40, wherein the instruction includes a trigger signal for operating the implantable device to emit an electrical pulse to the nerve.

42. The implantable device according to any one of claims 1 to 41, further comprising a sensor configured to detect a physiological state.

43. The implantable device according to any one of claims 1 to 42, wherein the fibrous tissue includes blood vessels.

44. A system comprising the implantable device according to any one of claims 1 to 43, and an interrogator comprising a second wireless communication system configured to wirelessly communicate with the wireless communication system of the implantable device.

45. The system according to claim 44, wherein the second wireless communication system comprises one or more ultrasonic transducers configured to transmit ultrasonic waves to the implantable device, and the ultrasonic waves supply power to the implantable device.

46. The system according to claim 44, wherein the second wireless communication system comprises one or more radio frequency antennas configured to transmit radio frequencies to the implantable device, and the radio frequencies supply power to the implantable device.

47. The system according to any one of claims 44 to 46, wherein the interrogator is configured to be worn externally.

48. A nerve cuff, a flexible helical substrate configured to at least partially wrap around fibrous tissue including a nerve, the flexible helical substrate being configurable between (a) a bent position by at least partially rewinding the nerve cuff and (b) a relaxed position; one or more electrodes disposed along the length of the helix of the flexible helical substrate; a handle portion attached to the flexible helical substrate and configured to apply a force to configure the flexible helical substrate from the relaxed position to the bent position; and including a nerve cuff.

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