Patent Application
20240108882
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, as well as methods of making the helical nerve cuff and the implantable device.
The peripheral nervous system of an individual operates activity of vital organs and physiological homeostasis with tight control. Electrical pulses (i.e., action potentials) transmitted through nerves can alter various physiological functions, such as pulse rates, inflammation, and bladder or bowel control. Certain medical conditions can arise when these neural signals fail to properly control the body, either by over-stimulating or under-stimulating target organs.
Invasive methods have been developed for treating abnormal physiological activity by controlling the electrical signals of the peripheral nervous system. Such methods can include implanting electrodes into the body of a patient, with the tips of the electrodes contacting target nerves. These electrodes generally have long leads that attach to an external device, which subject the patient to substantial risk of infection or displacement of the electrodes. Additionally, because many of the methods are so invasive, certain treatments are limited to clinical settings, and cannot be used as an at-home remedy. Wholly implantable devices have been developed for less invasive treatment, but such devices are too large to be placed in many locations of the body. Therefore, the implanted devices require the use of long leads, which can be displaced or break. Such implanted devices are also implanted to stimulate upstream nerves, such as the vagus nerve, which leads to significant side effects due off target electrical stimulation.
Previously developed nerve cuffs are larger or easily accessible peripheral nerves. However, such nerve cuffs may not be suitable or easily implantable on certain nerves.
A helical nerve cuff and an implantable device comprising the helical nerve cuff and a body comprising a wireless communication system are described herein. The body may be attached on 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 making the helical nerve cuff and the implantable device.
An implantable device may comprise a body comprising a wireless communication system; two or more electrodes in electrical communication with the wireless communication system configured to detect an electrophysiological signal transmitted by a nerve or emit an electrical pulse to the nerve; and a helical nerve cuff comprising at least one of the two or more electrodes, wherein the body is on the helical nerve cuff, and the helical nerve cuff is configured to at least partially wrap around a filamentous tissue comprising the nerve and position the at least one of the two or more electrodes in electrical communication with the nerve.
In some embodiments, the wireless communication system comprises an ultrasonic transducer. In some embodiments, the ultrasonic transducer is about 5 mm or less in length in the longest dimension. In some embodiments, the wireless communication system comprises two or more ultrasonic transducers.
In some embodiments, the wireless communication system comprises a radiofrequency antenna.
In some embodiments, the wireless communication system is configured to receive ultrasonic waves or radiofrequency waves, and convert energy from the ultrasonic waves or radiofrequency waves into an electrical energy that powers the device.
In some embodiments, the helical nerve cuff is configured to wrap around the nerve by at least one revolution. In some embodiments, the helical nerve cuff is configured to wrap around the nerve by about 1.3 to about 1.7 revolutions.
In some embodiments, the helical nerve cuff has a width that defines an inner surface, a first edge, and a second edges of the helical nerve cuff, and wherein at least a portion of the first edge contacts at least a portion of the second edge when the helical nerve cuff is in a relaxed position.
In some embodiments, the helical nerve cuff has a width that defines an inner surface, a first edge, and a second edges of the helical nerve cuff, and wherein the first edge does not contact the second edge when the helical nerve cuff is in a relaxed position.
In some embodiments, at least one of the two or more electrodes is positioned along the length of the helical nerve cuff. In some embodiments, the at least one of the two or more electrodes positioned along the length of the helical nerve cuff is positioned on an inner surface of the helical nerve cuff.
At least one of the electrodes on the helical nerve cuff can comprise one or more serpentine segments.
In some embodiments, the helical nerve cuff is flexible and is configurable in (a) a flexed position by at least partially unwinding the helical nerve cuff, and (b) a relaxed position.
In some embodiments, the implantable device further comprises one or more handle portions attached the helical nerve cuff or the body. In some embodiments, the handle portion comprises a loop. In some embodiments, the handle portion comprises 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 to a middle position along the length of the helical nerve cuff.
The implantable device can include a mount configured to receive the body and the helical nerve cuff, thereby attaching the body on the helical nerve cuff. Alternatively, the body is directly attached to the helical nerve cuff, such as on an outer surface of the helical nerve cuff or the body is attached to an end of the helical nerve cuff. In some embodiments, the body is attached to middle portion of the helical nerve cuff. In some embodiments, the body comprises an attachment end attached to the helical nerve cuff and an extension end extending from the attachment end.
In some embodiments, the helical nerve cuff comprises a right-handed helical portion. In some embodiments, the helical nerve cuff comprises a left-handed helical portion. In some embodiments, the helical nerve cuff comprises a right-handed helical portion joined to a left-handed helical portion. In some embodiments, the body attaches to the helical nerve cuff at a position proximal to where the right-handed helix portion is joined to the left-handed helical portion. In some embodiments, the right-handed helical portion is joined to a left-handed helical portion through a linear joining portion.
In some embodiments, the helical nerve cuff comprises one or more electrodes configured to emit an electrical pulse to the nerve. In some embodiments, the helical nerve cuff comprises one or more electrodes configured to detect the electrophysiological signal transmitted by the nerve. In some embodiments, the helical nerve cuff comprises two or more electrodes configured to detect the electrophysiological signal transmitted by the nerve.
In some embodiments, the nerve is a human splenic nerve. In some embodiments, the nerve is a human splanchnic nerve.
In some embodiments, the body comprises a housing. In some embodiments, the housing is configured as one of the two or more electrodes. In some embodiments, the housing comprises an acoustic window. In some embodiments, the housing contains an acoustically conductive material.
In some embodiments, the body comprises an integrated circuit electrically connected to the wireless communication system and the two or more electrodes. In some embodiments, the integrated circuit comprises an energy storage circuit comprising a capacitor.
In some embodiments, the body is about 8 mm or less in length in the longest dimension.
In some embodiments, the wireless communication system is configured to transmit data. In some embodiments, the wireless communication system is configured to emit an ultrasonic backscatter or radiofrequency backscatter that encodes the data. In some embodiments, the data comprises information related to a detected electrophysiological signal, a measured physiological condition, a device status, or an emitted electrical pulse.
In some embodiments, the wireless communication system is configured to receive instructions for operating the implantable device. In some embodiments, the instructions are encoded in ultrasonic waves or radiofrequency waves. In some embodiments, the instructions comprise a trigger signal that operates the implantable device to emit an electrical pulse to the nerve.
In some embodiments, the implantable device further comprises a sensor configured to detect a physiological condition. In some embodiments, the sensor is configured to detect temperature, pH, pressure, strain, or an analyte concentration.
In some embodiments, the fibrous tissue comprises a blood vessel.
Also described herein is a system, comprising any one of the implantable devices described above, 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, wherein the ultrasonic waves power the implantable medical device. In some embodiments, the second wireless communication system comprises one or more radiofrequency antennas configured to transmit radiofrequency waves to the implantable medical device, wherein the radiofrequency waves power the implantable medical device. In some embodiments, the interrogator is configured to be worn externally.
Further described herein is a nerve cuff, comprising a flexible helical substrate configured to at least partially wrap around a filamentous tissue comprising a nerve, and is configurable in (a) a flexed position by at least partially unwinding the helical nerve cuff, and (b) a relaxed position; one or more electrodes positioned along the length of the helical substrate; and a handle portion attached to the helical substrate configured to apply a force that configures the helical substrate in the flexed position.
In some embodiments of the helical nerve cuff, the handle portion comprises a loop. In some embodiments, the handle portion comprises 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 an end of the helical nerve cuff. In some embodiments, the helical nerve cuff 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 and the second handle portion are separated by a radial angle of about 900 to about 180° around a helical axis. In some embodiments, the first handle portion is attached to the second handle portion. In some embodiments, the helical nerve cuff comprises an additional handle portion attached on a middle position along the length of the helical nerve cuff.
The one or more electrodes of the helical nerve cuff can comprise one or more serpentine segments.
In some embodiments, the helical nerve cuff is configured to wrap around the nerve by at least one revolution. In some embodiments, the helical nerve cuff is configured to wrap around the nerve by about 1.3 to about 1.7 revolutions.
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 wherein at least a portion of the first edge contacts at least a portion of the second edge when the nerve cuff is in a relaxed position.
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 wherein the first edge does not contact the second edge when the nerve cuff is in a relaxed position.
In some embodiments, at least one of the one or more electrodes of the helical nerve cuff is positioned along the length of the helical nerve cuff. In some embodiments, the at least one of the one or more electrodes positioned along the length of the helical nerve cuff is positioned on an inner surface of the helical nerve cuff.
In some embodiments, the helical nerve cuff is configured to be unwound by at least one revolution.
In some embodiments, the helical nerve cuff comprises a right-handed helical portion. In some embodiments, the helical nerve cuff comprises a left-handed helical portion. In some embodiments, the helical nerve cuff comprises a right-handed helical portion joined to a left-handed helical portion. In some embodiments, the first helical portion is joined to a second portion through a connecting member. In some embodiments, the connecting member is a linear connecting member.
In some embodiments, the nerve cuff comprises one or more electrodes configured to emit an electrical pulse to the nerve. In some embodiments, the nerve cuff comprises one or more electrodes configured to detect the electrophysiological signal transmitted by the nerve. In some embodiments, the nerve cuff comprises two or more electrodes configured to detect the electrophysiological signal transmitted by the nerve. In some embodiments, the nerve cuff comprises one or more electrodes configured to detect the electrophysiological signal transmitted by the nerve, and one or more electrodes configured to emit an electrical pulse to the nerve, wherein at least one of the one or more electrodes configured to emit an electrical pulse to the nerve is wider than at least one of the one or more electrodes configured to detect the electrophysiological signal transmitted by the nerve.
In some embodiments of the helical nerve cuff, the helical nerve cuff is configured to at least partially wrap a filamentous tissue comprising a splenic nerve. In some embodiments of the helical nerve cuff, the helical nerve cuff is configured to at least partially wrap a filamentous tissue comprising a splanchnic nerve.
Also described herein is a method of implanting a helical nerve cuff comprising one or more electrodes, comprising: at least partially unwinding the helical nerve cuff; passing an end of the helical nerve cuff behind a fibrous tissue comprising 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.
Further described herein is a method of implanting an implantable device comprising a body comprising a wireless communication system on a helical nerve cuff comprising one or more electrodes, the method comprising at least partially unwinding the helical nerve cuff; passing an end of the helical nerve cuff behind a fibrous tissue comprising a nerve; and wrapping the helical nerve cuff around the fibrous tissue. In some embodiments, the method further comprises limiting movement of the body as the end of the helical nerve cuff is passed behind the fibrous tissue. In some embodiments, the body is held in an approximately steady position by holding a handle portion attached to the helical nerve cuff at a position proximal to the body or a handle portion attached to the body. In some embodiments, the implantable device is any one of the implantable devices described above.
In some embodiments of implanting the helical nerve cuff or the implantable device, the method comprises pulling the end of the helical nerve cuff passed behind the fibrous tissue.
In some embodiments of implanting the helical nerve cuff or the implantable device, the method comprises orienting the helical nerve cuff substantially parallel to the fibrous tissue.
In some embodiments of implanting the helical nerve cuff or the implantable device, the helical nerve cuff is at least partially unwound by pulling the end of the helical nerve cuff passed behind the fibrous tissue. In some embodiments of implanting the helical nerve cuff or the implantable device, the helical nerve cuff is at least partially unwound prior to pulling the end of the helical nerve cuff passed behind the fibrous tissue.
In some embodiments of implanting the helical nerve cuff or the implantable device, the end of the helical nerve cuff is passed behind the fibrous tissue from underneath the fibrous tissue.
In some embodiments of implanting the helical nerve cuff or the implantable device, the method comprises separating the fibrous tissue from surrounding tissue. In some embodiments, the fibrous tissue is separated from the surrounding tissue by circumferentially dissecting a portion of the fibrous tissue.
In some embodiments of implanting the helical nerve cuff or the implantable device, the end of the helical nerve cuff passed behind the fibrous tissue is pulled by pulling a handle portion attached to the end of the helical nerve cuff.
In some embodiments of implanting the helical nerve cuff or the implantable device, the fibrous tissue comprises a splenic nerve. In some embodiments of implanting the helical nerve cuff or the implantable device, the fibrous tissue comprises a splanchnic nerve.
Further described herein is a method of making an implantable device, comprising attaching a feedthrough to a housing; positioning a board assembly comprising a wireless communication system in the housing; attaching the housing to a first nerve cuff layer; attaching the first nerve cuff layer to a second nerve cuff layer comprising one or more electrodes; and electrically connecting the one or more electrodes of the nerve cuff to the board assembly through the feedthrough. In some embodiments, the feedthrough is attached to the housing prior to board assembly being positioned into the housing. In some embodiments, the feedthrough is attached to the board assembly before the board assembly is positioned into the housing. In some embodiments, the method comprises sealing the housing. In some embodiments, the method comprises attaching an acoustic window to the housing. In some embodiments, the acoustic window is attached to an open top of the housing after the board assembly is positioned within the housing. In some embodiments, the method comprises assembling the acoustic window by attaching a foil to a frame. In some embodiments, the method comprises filling the housing with an acoustically conductive material. In some embodiments, acoustically conductive material is filled into the housing through a port on the housing, the method comprising sealing the port. In some embodiments, the method comprises attaching the wireless communication system to the board assembly. In some embodiments, the wireless communication system comprises one or more ultrasonic transducers. In some embodiments, the board assembly comprises 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 a 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 comprises 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 comprises making the second nerve cuff layer by embedding one or more electrodes in a substrate material. In some embodiments, the method comprises wrapping the second nerve cuff layer around a mandrel, and attaching the second nerve cuff layer to the first nerve cuff layer while the second nerve cuff layer is wrapped around the mandrel.
Helical nerve cuffs containing one or more electrodes for stimulating a nerve and/or detecting an electrophysiological signal (such as an action potential, or absence of an action potential) transmitted by a nerve are described herein. Also described are implantable devices that include the helical nerve cuff, which include a body configured to operate the helical nerve cuff. The body includes a wireless communication system, which can wirelessly receive instructions from another device or wirelessly transmit information (such as information about a detected electrophysiological signal or other physiological feature) to another device. Also described are methods of implanting the helical nerve cuff and implantable device, as well as methods of making the helical nerve cuff and implantable device.
The nerve cuff can include a helical substrate configured to at least partially wrap around a filamentous tissue comprising a nerve, and one or more electrodes positioned on an inner surface (for example, along the length) of the helical substrate. The helical nerve cuff can be implanted in a subject such that the electrode is in electrical communication with the nerve. The electrode(s) may be configured to detect an electrophysiological signal transmitted by a nerve or 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 on a small and/or difficult to access nerve of the subject, such as the splenic nerve or a splanchnic nerve, and the helical design of the nerve cuff allows for easier implantation.
The implantable device includes a body having a wireless communication system (which may include, for example, one or more ultrasonic transducers or one or more radiofrequency (RF) antennas), two or more electrodes in electrical communication with the wireless communication system, and the helical nerve cuff. The two or more electrodes are configured to detect an electrophysiological signal transmitted by a nerve or emit an electrical pulse to the nerve, and one or more of the electrodes are positioned on the helical nerve cuff. The body may include an electrically conductive housing, which itself is optionally one of the electrodes.
The helical nerve cuff may be implanted in a subject by circumferentially dissecting a portion of a fibrous tissue comprising a nerve (which may further include a blood vessel, i.e., a neurovascular bundle), threading an end of the nerve cuff through the back side of the fibrous tissue, and rotating the helical nerve cuff to position the nerve cuff around the fibrous tissue. The helical nerve cuff may be attached to a body, and the body of the device may be positioned in front of the fibrous tissue when the cuff is positioned around the fibrous tissue. If the helical nerve cuff includes a handle portion attached to an end of the helical nerve, the handle portion may be threaded through the back side of the fibrous tissue to lead the end of the helical nerve cuff through the back side of the fibrous tissue.
The handle portion attached to the helical nerve cuff allows for carful manipulation of the nerve cuff in the small compartment space of the nerve when nerve cuff is being implanted. A surgical grasping tool can be used to grasp the handle portion to thread it through to the back side of the circumferentially dissected fibrous tissue. In some embodiments, the nerve huff includes a second handle portion on the opposite end of the helical nerve cuff. The second handle portion may also be grasped by a surgical grasping tool to guide the nerve cuff in place, unwind the helix during implantation, or to rotate the helical nerve cuff to correctly position the device.
As used herein, the singular forms “a,” “an,” and “the” include the plural reference unless the context clearly dictates otherwise.
Reference to “about” or “approximately” a value or parameter herein includes (and describes) variations that are directed to that value or parameter per se. For example, description referring to “about X” includes description of “X.”
It is understood that aspects and variations of the invention described herein include “consisting” and/or “consisting essentially of” aspects and variations.
The term “subject” and “patient” are used interchangeably herein to refer to a vertebrate animal.
The terms “treat,” “treating,” and “treatment” are used synonymously herein to refer to any action providing a benefit to a subject afflicted with a disease state or condition, including improvement in the condition through lessening, inhibition, suppression, or elimination of at least one symptom, delay in progression of the disease or condition, delay in recurrence of the disease or condition, or inhibition of the disease or condition.
Where a range of values is provided, it is to be understood that each intervening value between the upper and lower limit of that range, and any other stated or intervening value in that stated range, is encompassed within the scope of the present disclosure. Where the stated range includes upper or lower limits, ranges excluding either of those included limits are also included in the present disclosure.
It is to be understood that one, some or all of the properties of the various embodiments described herein may be combined to form other embodiments of the present invention. The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.
Features and preferences described above in relation to “embodiments” are distinct preferences and are not limited only to that particular embodiment; they may be freely combined with features from other embodiments, where technically feasible, and may form preferred combinations of features. The description is presented to enable one of ordinary skill in the art to make and use the invention and is provided in the context of a patent application and its requirements. Various modifications to the described embodiments will be readily apparent to those persons skilled in the art and the generic principles herein may be applied to other embodiments. Thus, the present invention is not intended to be limited to the embodiment shown but is to be accorded the widest scope consistent with the principles and features described herein.
The helical nerve cuff includes a helical substrate configured to at least partially wrap around a filamentous tissue comprising a nerve, and one or more electrodes positioned 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.
The nerve cuff is configured to at least partially wrap around a filamentous tissue that includes a nerve. The filamentous tissue may include filamentous tissue in addition to the nerve, such as a vessel (e.g., a neurovascular bundle). For example, the splenic nerve is closely associated with the splenic artery and the nerve cuff may be configured to at least partially wrap around 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 filamentous tissue, which may different depending on the species of the subject, the target nerve, or other anatomical differences within the subject (e.g., the size of the nerve within the specific subject. By way of example, the inner diameter may be between about 1 mm and about 8 mm in diameter (such as between about 1 mm and about 2 mm, about 2 mm and about 3 mm, about 3 mm and about 4 mm, about 4 mm and about 5 mm, about 5 mm and about 6 mm, about 6 mm and about 7 mm, or about 7 mm and about 8 mm in diameter).
The helical nerve cuff may be configured to wrap around the nerve by at least one revolution. For example, the helical nerve cuff may wrap around the nerve by about 1 to about 4 revolutions, such as about 1 to about 1.3 revolutions, about 1.3 to about 1.7 revolutions, about 1.7 to about 2 revolutions, about 2 to about 2.5 revolutions, about 2.5 to about 3 revolutions, or about 3 to about 4 revolutions. In some embodiments, the helical nerve cuff is configured to wrap around the nerve by about 1.5 revolutions.
The substrate of the nerve cuff is an elongated material wound into 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, with optionally tapered or rounded ends. The width of the substrates define edges, and the edges may or may not contact each other as the substrate winds in the helical shape when the nerve cuff is in a relaxed position. For example, in some embodiments, a gap may or may not separate the revolutions 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 wherein at least a portion of the first edge contacts at least a portion of the second edge when the nerve cuff is in a 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 wherein the first edge does not contact the second edge when the nerve cuff is in a relaxed position.
The substrate of the helical nerve cuff is made from an insulating material, which may be a biocompatible and/or elastomeric material. Exemplary substrate materials include, but are not limited to, silicone, silicone rubber, polydimethylsioloxane (PDMS), a urethane polymer, a poly(p-xylylene)polymer (such as a poly(p-xylylene) polymer sold under the tradename PARYLENE®), or a polyimide.
In some embodiments, the substrate of the helical nerve cuff may include two or more layers, which may be of the same material or of different materials. The layers can included an inner layer that forms the inner surface of the helical nerve cuff and contacts the fibrous tissue, and an outer layer that forms that forms the outer surface of the helical nerve cuff. An electrically conductive material may be positioned between the inner and outer layers, which can form the electrodes of the helical nerve cuff. For example, the inner layer can include one or more opening on the inner surface to expose the electrically conductive material, which 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 tensile force than the outer layer when the helical nerve cuff is in a flexed configuration, which forces the substrate to curl inwards when the helical nerve cuff is in a relaxed configuration.
The width of the nerve cuff can depend on the on the length of nerve cuff (i.e., the maximal distance along an axis running through the center of the helix between the ends of the nerve cuff), the number of revolutions of the substrate, and size of a gap between substrate revolutions (if any). In some embodiments, the length of the nerve cuff is about 4 mm to about 20 mm (such as about 4 mm to about 7 mm, about 7 m to about 10 mm, about 10 mm to about 13 mm, about 13 mm to about 16 mm, or about 16 mm to about 20 mm). In some embodiments, the width (or the inner width) of the substrate is about 2 mm to about 8 mm (such as about 2 mm to about 4 mm, about 4 mm to about 6 mm, or about 6 mm to about 8 mm).
The nerve cuff may be flexible, which allows for manipulation of the nerve cuff upon implantation. For example, in some embodiments, the helical nerve cuff can be configured in a flexed position by at least partially unwinding the helical nerve cuff, and a relaxed position with the helical nerve cuff in a helical configuration.
The nerve cuff may include a right-handed helical portion, a left-handed helical portion, or both a right-handed helical portion a left-handed helical portion. For example, in some embodiments, the nerve cuff may include a right-handed helical portion joined to a left-handed helical portion, either directly or through a connecting member (which may be linear, curved, or hinged).
The one or more electrodes of the nerve cuff may be positioned on the inner surface of the nerve cuff substrate, and may be uncoated or coated with an electrically conductive material (e.g., electroplated with a poly(3,4-ethylenedioxythiophene) (PEDOT) polymer or other electrically conductive polymer or a metal to improve electrical characteristics of the electrode). In some embodiments, one or more of the electrodes are point electrodes. In some embodiments, one or more of the electrodes may be elongated, and may be positioned, for example, along the length of the helical substrate. The electrodes may terminate before the end of the substrate, at the end of the substrate, or beyond the end of the substrate. The one or more electrodes may be connected to a feed through on the helical nerve cuff, which allows the electrodes to be electrically connected to the outer surface of the substrate or a body attached to the outer surface of the nerve cuff.
The nerve cuff includes one or more electrodes, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more electrodes. In some embodiments, one or more of the electrodes are configured to emit an electrical pulse to the nerve. In some embodiments, the nerve cuff includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more electrodes configured to emit an electrical pulse to the nerve. In some embodiments, one or more of the electrodes are configured to detect an electrophysiological signal transmitted by the nerve. In some embodiments, the nerve cuff includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more electrodes configured to detect an electrophysiological signal transmitted by the nerve. In some embodiments, one or more electrodes are configured to emit an electrical pulse to the nerve, and one or more of the electrodes are configured to detect an electrophysiological signal transmitted by the nerve. In some embodiments, an electrode configured to emit an electrical pulse is wider than an electrode configured to detect an electrophysiological signal. Electrodes of the helical nerve cuff (having more than one electrode) may be positioned along the length of the helical nerve cuff alongside each other, or in different directions.
Optionally, one or more of the electrodes on the nerve cuff has a serpentine configuration, or one or more (e.g., 2, 3, 4, or more) serpentine segments.
The optional handle portion is configured to be grasped by a surgical grasping tool (e.g., forceps, hook, or other grasping or gripping instrument), and may be useful for manipulating the helical nerve cuff during implantation. The handle portion may extend from 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 within the handle portion or by forming a loop by either end of the handle portion being attached to the substrate. In some embodiments, the handle portion comprises a flexible filament (such as a thread, string, cord, suture, or wire), which is optionally biodegradable once implanted within the subject. In some embodiments, the handle portion comprises a bioabsorbable material, such as polyglycolide, polydioxanone, polycaprolactone, or copolymers thereof.
The optional handle portion may be attached to the nerve cuff proximal to the end of the nerve cuff (e.g., at the tip of the helical nerve cuff). The nerve cuff optionally includes more than one handle portion. For example, the helical portion may include an additional handle portion proximal to the opposite end of the helical substrate and/or an additional handle portion proximal to a middle portion of the helical substrate. If the helical nerve cuff is attached to a body, as further discussed herein, the one of the handle portions may be proximal to the body or distal to the body. By way of example, in some embodiments, the body is attached proximal to a 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 a 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, a body is attached proximal to a first end of the helical nerve cuff, and a first handle portion is attached proximal to the body and a second handle portion is attached proximal to a second end of the helical nerve cuff. In some embodiments, the body is attached to a middle portion of the helical nerve cuff, a first handle portion is attached proximal to a first end of the helical nerve cuff, a second handle portion is attached proximal to the body, and optionally a third handle portion is attached proximal to the second end of the helical nerve cuff.
Optionally, two or more handle portions attached to the nerve cuff are joined together. For example, a first handle portion includes a first end attached proximal to a first end of the helical nerve cuff, a second handle portion includes a first end attached proximal to a 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 together. 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° (for example, about 900 to about 120°, about 1200 to about 150°, or about 1500 to about 180°) around a helical axis.
The helical nerve cuff can optionally include a mount configured to receive a body. The mount provide additional stability to the device so that the body does not disconnect from the helical nerve cuff. The mount can attach 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 the end of the substrate of the helical nerve cuff. The one or more electrodes of the helical nerve cuff may extend beyond a terminus of the substrate such that they can be positioned deeper within the substrate receiving port than the substrate itself. The mount can also include a body receiving port sized and shaped to receive a body or housing containing the body. The mount can therefore provide stable attachment of the body to the substrate of the helical nerve cuff. As further described herein, the body can include components for operating the one or more electrodes on the helical nerve cuff. Accordingly, the mount provides an electrical connection between the body and the one or more electrodes of the helical nerve cuff. This may occur, for example, by allowing a direct connection between the one or more electrodes of the helical nerve cuff and the body. For example, the mount may include an opening that connects the substrate receiving port and the body receiving port to allow for the electrical connection between the body and the one or more electrodes. Alternatively, the mount can includes one or more electrical feedthroughs that intermediate the electrical connection between the body and the one or more electrodes on the helical nerve cuff.
The mount can be made of an insulating material, which may be a biocompatible and/or elastomeric material. Exemplary materials for the mount include, but are not limited to, silicone, silicone rubber, polyether ether ketone (PEEK), polydimethylsioloxane (PDMS), a urethane polymer, a poly(p-xylylene)polymer (such as a poly(p-xylylene) polymer sold under the tradename PARYLENE®), or a polyimide.
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 a rodent (such as a rat or mouse). The helical nerve cuff may be configured to at least partially wrap around a filamentous tissue (such as a peripheral nerve, or a filamentous tissue comprising a peripheral nerve, such as a neurovascular bundle) within any of these animals, or others. For example, in some embodiments, the helical nerve cuff is configured to at least partially wrap around a human peripheral nerve, such as a human splenic nerve, or a 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 a 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 a vagus nerve, a mesenteric nerve, a splenic nerve, a sciatic nerve, a tibial nerve, a pudendal nerve, a celiac ganglion, a sacral nerve, or any branch thereof.
An implantable device, which may be used to detect and electrophysiological signal transmitted by a nerve or emit an electrical pulse to a nerve, can include a body attached to a helical nerve cuff. The body is attached to the helical nerve cuff without an interceding lead between the body and the helical nerve cuff. That is, the body is directly attached to the outer surface of the helical nerve cuff to join the body to the nerve cuff. By securing the body to the helical nerve cuff, the never cuff and the body may be simultaneously positioned upon implantation. The body may include a wireless communication system, which is electrically connected to two or more electrodes. The two or more electrodes can be configured to detect an electrophysiological signal transmitted by a nerve or emit an electrical pulse to the nerve, and at least one of the electrodes is included on the helical nerve cuff. The helical nerve cuff may be, for example, a helical nerve cuff as described in further detail herein. The implantable device is full implantable; that is, no wires or leads connect outside the body of the subject after implantation.
The two or more electrodes of the device, including one or more of the electrodes on the helical nerve cuff, 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 through integrated circuit. The integrated circuit may be configured to operate the wireless communication system of the device body, and can operate the two or more electrodes of the implantable device to detect the electrophysiological signal and/or emit an electrical pulse. Optionally, the implantable device includes one or more sensors configured to detect a physiological condition (such as temperature sensor, an oxygen sensor, a pH sensor, a strain sensor, a pressure sensor, an impedance sensor, or a sensor that can detect a concentration of an analyte).
The body of the implantable device includes a wireless communication system, which can communicate with a separate device (such as an external interrogator or another implantable device). For example, the wireless communication may be configured to receive instructions for emitting one or more electrical pulses to the nerve and/or transmit information, such as data associated with detected electrophysiological signal transmitted by the nerve and/or data associated one or more physiological conditions (e.g., pulse, temperature, pressure, presence or concentration of an analyte, etc.). The wireless communication system can include, for example one or more ultrasonic transducers or one or more radiofrequency antennas. The wireless communication system may also be configured to receive energy (for example, through ultrasonic or radiofrequency (RF)) from another device, which can be used to power the implantable device.
Information about the detected electrophysiological signal or physiological condition may be transmitted using the wireless communication system to a receiving device. For example, the wireless communication system may include two or more ultrasonic transducers, which can be operated to encode information about the detected electrophysiological signal or physiological condition using ultrasonic backscatter waves or radiofrequency backscatter waves. Exemplary implantable devices that can detect an electrophysiological signal and encode information related to the detected electrophysiological signal are described in WO 2018/009910 A2. Exemplary implantable devices that can be operated using ultrasonic waves to emit an electrical pulse are described in WO 2018/009912 A2. Exemplary implantable devices that are powered by ultrasonic waves and can emit an ultrasonic backscatter encoding a detected physiological condition are described in WO 2018/009905 A2 and WO 2018/009911 A2.
An integrated circuit included in the device body can electrically connect and communicate between the electrodes or sensor and the wireless communication system (e.g., the 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, which modulates an electrical current flowing through the wireless communication system (e.g., one or more ultrasonic transducers or one or more radiofrequency antennas) to encode information in the electrical current. The modulated electrical current affects backscatter waves (e.g., ultrasonic backscatter waves or radiofrequency backscatter waves) emitted by the wireless communication system, and the backscatter waves encode the information.
The wireless communication system can be configured to receive instructions for operating the implantable device. The instructions may be transmitted, for example, by a separate device, such as an interrogator. By way of example, ultrasonic waves received by the implantable device (for example, those 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 may 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 may include, for example, information relating to when the electrical pulse should be emitted, a pulse frequency, a pulse power or voltage, a pulse shape, and/or a pulse duration.
In some embodiments, the implantable device can also be operated to transmit information (i.e., uplink communication), which can be received by the interrogator, through the wireless communication system. In some embodiments, the wireless communication system is configured to actively generate a communication signal (e.g., ultrasonic waves or radiofrequency waves) that encode the information. In some embodiments, the wireless communication system is configured to transmit information encoded on backscatter waves (e.g., ultrasonic backscatter waves or RF backscatter waves). Backscatter communication provides a lower power method of transmitting information, which is particularly beneficial for small devices to minimize energy sues. By way of example, the wireless communication system may include one or more ultrasonic transducers configured to receive ultrasonic waves and emit an ultrasonic backscatter, which can encode information transmitted by the implantable device. Current flows through the ultrasonic transducer, which can be modulated to encode the information. The current may be modulated directly, for example by passing the current through a sensor that modulates the current, or indirectly, for example by modulating the current using a modulation circuit based on a detected physiological condition or an electrophysiological pulse.
In some embodiments, the information transmitted by the wireless communication system includes information unrelated to a detected physiological condition or electrophysiological pules detected by the implantable device. For example, the information can include one or more of: information related to the status of the implantable device or a confirmation signal that confirms an electrical pulse was emitted, the power, frequency, voltage, duration, or other information related to an emitted electrical pulse, and/or an identification code for the implantable device. Optionally, the integrated circuit is configured to digitize the information, and the wireless communication system can transmit the digitized information.
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 in backscatter waves (e.g., ultrasonic backscatter or radiofrequency backscatter). The backscatter can be received by the interrogator, for example, and deciphered to determine the encoded information. Additional details about 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 incorporated herein by reference for all purposes. The 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 or contained within the integrated circuit.
An interrogator can transmit energy waves (e.g., ultrasonic waves or radiofrequency waves), which are received by the wireless communication system of the device to generate an electrical current flowing through the wireless communication system (e.g., to generate an electrical current flowing through the ultrasonic transducer or the radiofrequency antenna). The flowing current can then generate backscatter waves that are emitted by the wireless communication system. The modulation circuit can be configured to modulate the current flowing through the wireless communication system to encode the information. For example, the modulation circuit may be electrically connected to an ultrasonic transducer, which received ultrasonic waves from an interrogator. The current generated by the received ultrasonic waves can be modulated using the modulation circuit to encode the information, which results in ultrasonic backscatter waves emitted by the ultrasonic transducer to encode the information. A similar approach may be taken with a radiofrequency antenna that receives radiofrequency waves. 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 alter the impedance of a current flowing through the wireless communication system, and variation in current flowing through the wireless communication system encodes the information. In some embodiments, information encoded in the backscatter waves includes information related to an electrophysiological signal transmitted by the nerve, an electrical pulse emitted by the implantable device, or a physiological condition detected by a sensor of the implantable device. In some embodiments, information encoded in the backscatter waves includes a unique identifier for the implantable device. This can be useful, for example, to ensure the interrogator is in communication with the correct implantable device when a plurality of implantable devices is implanted in the subject. In some embodiments, the information encoded in the backscatter waves includes a verification signal that verifies an electrical pulse was emitted by the implantable device. In some embodiments, the information encoded in the backscatter waves includes an amount of energy stored or a voltage in the energy storage circuit (or one or more capacitors in the energy storage circuit). In some embodiments, the information encoded in the backscatter waves includes a detected impedance. Changes in the impedance measurement can identify scarring tissue or degradation of the electrodes over time.
In some embodiments, the modulation circuit is operated using a digital circuit or a mixed-signal integrated circuit (which may be part of the integrated circuit), which can actively encode the information in a digitized or analog signal. The digital circuit or mixed-signal integrated circuit may include a memory and one or more circuit blocks, systems, or processors for operating the implantable device. These systems can include, for example, an onboard microcontroller or processor, a finite state machine implementation, or digital circuits capable of executing one or more programs stored on the implant or provided via ultrasonic communication between interrogator and implantable device. In some embodiments, the digital circuit or a mixed-signal integrated circuit includes an analog-to-digital converter (ADC), which can convert analog signal encoded in the ultrasonic waves emitted from the interrogator so that the signal can be processed by the digital circuit or the mixed-signal integrated circuit. The digital circuit or mixed-signal integrated circuit can also operate the power circuit, for example to generate the electrical pulse to stimulate the tissue. In some embodiments, the digital circuit or the mixed-signal integrated circuit receives the trigger signal encoded in the ultrasonic waves transmitted by the interrogator, and operates the power circuit to discharge the electrical pulse in response to the trigger signal.
In some embodiments, the 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, wherein the second ultrasonic transducer is positioned so that the second polarization axis is orthogonal to the first polarization axis, and wherein the first ultrasonic transducer and the second ultrasonic transducer are configured to receive ultrasonic waves that power the device and emit an 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, wherein the second ultrasonic transducer is positioned so that the second polarization axis is orthogonal to the first polarization axis and the third polarization axis, wherein the third ultrasonic transducer is positioned so that the third polarization axis is orthogonal to the first polarization and the second polarization axis, and wherein the first ultrasonic transducer and the second ultrasonic transducer are configured to receive ultrasonic waves that power the device and emit an ultrasonic backscatter.
The ultrasonic transducer, if included in the wireless communication system, can be a micro-machined ultrasonic transducer, such as a capacitive micro-machined ultrasonic transducer (CMUT) or a piezoelectric micro-machined ultrasonic transducer (PMUT), or can be a bulk piezoelectric transducer. Bulk piezoelectric transducers can be any natural or synthetic material, such as a crystal, 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 tantalite (LiTaO3), potassium niobate (KNbO3), sodium tungstate (Na2WO3), bismuth ferrite (BiFeO3), polyvinylidene (di)fluoride (PVDF), and lead magnesium niobate-lead titanate (PMN-PT).
In some embodiments, the bulk piezoelectric transducer is approximately cubic (i.e., an aspect ratio of about 1:1:1 (length:width:height). In some embodiments, the piezoelectric transducer is plate-like, with an aspect ratio of about 5:5:1 or greater in either the length or width aspect, such as about 7:5:1 or greater, or about 10:10:1 or greater. In some embodiments, the bulk piezoelectric transducer is long and narrow, with an aspect ratio of about 3:1:1 or greater, and where the longest dimension is aligned to the direction of the ultrasonic backscatter waves (i.e., the polarization axis). In some embodiments, one dimension of the bulk piezoelectric transducer is equal to one half of the wavelength (k) corresponding to the drive frequency or resonant frequency of the transducer. At the resonant frequency, the ultrasound wave impinging on either the face of the transducer will undergo a 180° phase shift to reach the opposite phase, causing the largest displacement between the two faces. In some embodiments, the height of the piezoelectric transducer is about 10 μm to about 1000 μm (such as about 40 μm to about 400 μm, about 100 m to about 250 μm, about 250 μm to about 500 μm, or about 500 m to about 1000 μm). In some embodiments, the height of the piezoelectric transducer is about 5 mm or less (such as about 4 mm or less, about 3 mm or less, about 2 mm or less, about 1 mm or less, about 500 μm or less, about 400 μm or less, 250 μm or less, about 100 μm or less, or about 40 μm or less). In some embodiments, the height of the piezoelectric transducer is about 20 μm or more (such as about 40 μm or more, about 100 μm or more, about 250 μm or more, about 400 μm or more, about 500 μm or more, about 1 mm or more, about 2 mm or more, about 3 mm or more, or about 4 mm or more) in length. In some embodiments, the ultrasonic transducer has a length of about 5 mm or less such as about 4 mm or less, about 3 mm or less, about 2 mm or less, about 1 mm or less, about 500 μm or less, about 400 μm or less, 250 μm or less, about 100 μm or less, or about 40 μm or less) in the longest dimension. In some embodiments, the ultrasonic transducer has a length of about 20 μm or more (such as about 40 μm or more, about 100 μm or more, about 250 μm or more, about 400 μm or more, about 500 μm or more, about 1 mm or more, about 2 mm or more, about 3 mm or more, or about 4 mm or more) in the longest dimension.
The ultrasonic transducer, if included in the wireless communication system, can be connected two electrodes to allow electrical communication with the integrated circuit. The first electrode is attached to a first face of the transducer and the second electrode is attached to a second face of the transducer, wherein the first face and the second face are opposite sides of the transducer along one dimension. In some embodiments, the electrodes comprise 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 motion of the transducer.
The implantable device may be configured to wirelessly receive energy and convert the energy into an electrical energy, which may be used to power the device. The wireless communication system may be used to wireless receive the energy, or a separate system may be configured to receive the energy. For example, an ultrasonic transducer (which may be an ultrasonic transducer contained within the wireless communication system or a different ultrasonic transducer) can be configured to receive ultrasonic waves and convert energy from the ultrasonic waves into an electrical energy. In some embodiments, an RF antenna (which may be an RF antenna contained 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 an electrical energy. The electrical energy is transmitted to the integrated circuit to power the device. The electrical energy may power the device directly, or the integrated circuit may operate a power circuit to store the energy for later use.
In some embodiments, the integrated circuit includes a power circuit, which can include an energy storage circuit. The energy storage circuit may include a battery, or an alternative energy storage device such as one or more capacitors. The implantable device is preferably batteryless, and may instead rely on one or more capacitors. By way of example, energy from ultrasonic waves or radiofrequency waves received by the implantable device (for example, through the wireless communication system) is convened into a current, and can be stored in the energy storage circuit. The energy can be used to operate the implantable device, such as providing power to the digital circuit, the modulation circuit, or one or more amplifiers, or can be used to generate the electrical pulse used to stimulate the tissue. In some embodiments, the power circuit further includes, for example, a rectifier and/or a charge pump.
The integrated circuit may be configured to operate the two or more electrodes of the device configured to detect an electrophysiological signal transmitted by a nerve or emit an electrical pulse to the nerve, and at least one of the electrodes is included on the helical nerve cuff. The electrodes may be positioned on the helical nerve cuff, 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 working electrodes on the helical nerve cuff, and the housing may be configured as a counter electrode. Accordingly, 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 feedthroughs.
In some embodiments, the implantable device includes one or more sensors configured to detect a physiological condition. The sensor(s) may be, for example, included as part of the body of the device or on the helical nerve cuff. The sensors are configured to detect a physiological condition, such as temperature, oxygen concentration, pH, an analyte (such as glucose), strain, or pressure. Variation in the physiological condition modulates impedance, which in turn modulates current flowing through a detection circuit electrically connected to or part of the integrated circuit. The implantable device may comprise one or more (such as 2, 3, 4, 5 or more) sensors, which may 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 the backscatter waves emitted by the wireless communication system, which can be deciphered by an external computing system (such as the interrogator).
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 an end of the helical nerve cuff, or at a middle portion of the helical nerve cuff. Optionally, a handle portion may be attached to the helical nerve cuff, and may 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 attached to the helical nerve cuff, and a second handle portion attached to the helical nerve cuff at a distal position, such as at an end of the helical nerve cuff. Examples of an implantable device body attached to a helical nerve cuff is shown in
The body (or housing) of the of the implantable device may be attached to the helical nerve cuff through an adhesive (e.g., an epoxy, glue, cement, solder, or other binder), one or more fasteners (e.g., a staple, screw, bolt, clap, rivet, pin, rod, etc.), or any other suitable means to securely attach the body to the helical nerve cuff to ensure that it does not become separated from the nerve cuff after implantation. The body (or housing) may be directly attached to the nerve cuff.
The body can include a housing, which can include a base, one or more sidewalls, and a top. The housing is optionally made from an electrically conductive material and may be configured as one of the one or more electrodes of the implantable device configured to detect an electrophysiological signal transmitted by a nerve or emit an electrical pulse to the 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 an operating electrode. The housing is made from a bioinert material, such as a bioinert metal (e.g., steel or titanium) or a bioinert ceramic (e.g., titania or alumina). The housing is preferably hermetically sealed, which prevents body fluids from entering the body.
An acoustic window can be included in the housing of the body, for example on the top of the housing (see
The housing may be filled with an acoustically conductive material, such as a polymer or oil (such as a silicone oil). The material can fill empty space within the housing to reduce acoustic impedance mismatch between the tissue outside of the housing and within the housing. Accordingly, the body of the device is preferably void of air or vacuum. A port can be included on the housing, for example on the sidewall of the housing (see
The housing of the implantable device is relatively small, which allows for comfortable and long-term implantation while limiting tissue inflammation that is often associated with implantable devices. In some embodiments, the longest dimension of the housing of the device is about 8 mm or less, about 7 mm or less, about 6 m 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, about 0.1 mm or less in length. In some embodiments, the longest dimension of the housing of the device is about 0.05 mm or longer, about 0.1 mm or longer, about 0.3 mm or longer, about 0.5 mm or longer, about 1 mm or longer, about 2 mm or longer, about 3 mm or longer, about 4 mm or longer, about 5 mm or longer, about 6 mm or longer, or about 7 mm or longer in the longest dimension of the device. In some embodiments, the longest dimension of the housing of the device is about 0.3 mm to about 8 mm in length, about 1 mm to about 7 mm in length, about 2 mm to about 6 mm in length, or about 3 mm to about 5 mm in length. In some embodiments, the housing of the implantable device has a volume of about 10 mm3 or less (such as about 8 mm3 or less, 6 mm3 or less, 4 mm3 or less, or 3 mm3 or less). In some embodiments, the housing of the implantable device has a volume of about 0.5 mm3 to about 8 mm3, about 1 mm3 to about 7 mm3, about 2 mm3 to about 6 mm3, or about 3 mm3 to about 5 mm3.
The housing (such as the bottom of the housing) can include a feedthrough port, which may be aligned with the feedthrough port of the nerve cuff. A feedthrough can electrically connect the one or more electrodes of the nerve cuff to components of the body within the housing. For example, the feedthrough may be electrically connected to an integrated circuit and/or the wireless communication system of the device body.
In some embodiments, the implantable device is implanted in a subject. The subject can be for example, a mammal. In some embodiments, the subject is a human, dog, cat, horse, cow, pig, sheep, goat, monkey, or a rodent (such as a rat or mouse). The helical nerve cuff may be configured to at least partially wrap around a filamentous tissue (such as a peripheral nerve, or a filamentous tissue comprising a peripheral nerve, such as a neurovascular bundle) within any of these animals, or others. For example, in some embodiments, the helical nerve cuff is configured to at least partially wrap around a human peripheral nerve, such as a human splenic nerve, or 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 a vagus nerve, a mesenteric nerve, a splenic nerve, a sciatic nerve, a tibial nerve, a pudendal nerve, a celiac ganglion, a sacral nerve, or any branch thereof.
The interrogator can wirelessly communicate with one or more implantable devices using the wireless communication system of the implantable device. Wireless communication may include wirelessly receiving information from the implantable device, wirelessly transmitting instructions 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 that instructs the implantable device to emit an electrical pulse. In some embodiments, the interrogator further receives ultrasonic backscatter from the implantable device, which encodes information transmitted by the implantable device. The information may include, for example, information related to a detected electrophysiological pulse, an electrical pulse emitted by the implantable device, and/or a measured physiological condition.
In some embodiments, the interrogator wirelessly transmits energy (such as ultrasonic waves or radiofrequency waves) to power the implantable device. For example, the interrogator may transmit ultrasonic waves or RF waves to the implantable device, which can convert energy from the received waves into an electrical energy that is used to power the device, either immediately or by storing the energy in a power circuit.
The interrogator may include one or more ultrasonic transducers or radiofrequency antennas (depending, for example, if the implantable device includes an ultrasonic transducer or radiofrequency antenna in its wireless communication system), which can operate as a transmitter and/or a receiver (or as a transceiver, which can be configured to alternatively transmit or receive the ultrasonic waves). 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 transmitting function is separated from the receiving function on separate devices. That is, optionally, the interrogator comprises 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 in the array can have regular spacing, irregular spacing, or be sparsely placed. In some embodiments the array is flexible. In some embodiments the array is planar, and in some embodiments the array is non-planar.
An exemplary interrogator is shown in
The interrogator shown in
In some embodiments, the transducer connected to the channel is configured only to receive or only to transmit ultrasonic waves, and the switch is optionally omitted from the channel. The channel can include a delay control, which operates to control the transmitted ultrasonic waves. The delay control can control, for example, the phase shift, time delay, pulse frequency and/or wave shape (including amplitude and wavelength). The delay control can be connected to a level shifter, which shifts input pulses from the delay control to a higher voltage used by the transducer to transmit the ultrasonic waves. In some embodiments, the data representing the wave shape and frequency for each channel can be stored in a ‘wave table’. This allows the transmit waveform on each channel to be different. Then, delay control and level shifters can be used to ‘stream’ out this data to the actual transmit signals to the transducer array. In some embodiments, the transmit waveform for each channel can be produced directly by a high-speed serial output of a microcontroller or other digital system and sent to the transducer element through a level shifter or high-voltage amplifier. In some embodiments, the ASIC includes a charge pump (illustrated in
In the ultrasound receiving circuit, the received ultrasonic waves are converted to current by the transducers (set in a receiving mode), which is transmitted to a data capture circuit. In some embodiments, an amplifier, an analog-to-digital converter (ADC), a variable-gain-amplifier, or a time-gain-controlled variable-gain-amplifier which compensates for tissue loss, and/or a band pass filter is included in the receiving circuit. The ASIC can draw power from a power supply, such as a battery (which is preferred for a wearable embodiment of the interrogator). In the embodiment illustrated in
In some embodiments, the interrogator is implantable. In some embodiments, the interrogator is external (i.e., not implanted). By way of example, the external interrogator can be a wearable, which may be fixed to the body by a strap or adhesive. In another example, the external interrogator can be a wand, which may be held by a user (such as a healthcare professional). In some embodiments, the interrogator can be held to the body via suture, simple surface tension, a clothing-based fixation device such as a cloth wrap, a sleeve, an elastic band, or by sub-cutaneous fixation. The transducer or transducer array of the interrogator may be positioned separately from the rest of the transducer. For example, the transducer array can be fixed to the skin of a subject at a first location (such as proximal to one or more implanted devices), and the rest of the interrogator may be located at a second location, with a wire tethering the transducer or transducer array to the rest of the interrogator.
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 computed as:
where D is the size of the aperture and X is the wavelength of ultrasound in the propagation medium (i.e., the tissue). As understood in the art, the Rayleigh distance is the distance at which the beam radiated by the array is fully formed. That is, the pressure field converges to a natural focus at the Rayleigh distance in order to maximize the received power. Therefore, in some embodiments, the implantable device is approximately the same distance from the transducer array as the Rayleigh distance.
The individual transducers in a transducer array can be modulated to control the Raleigh distance and the position of the beam of ultrasonic waves emitted by the transducer array through a process of beamforming or beam steering. Techniques such as linearly constrained minimum variance (LCMV) beamforming can be used to communicate a plurality of implantable devices with an external ultrasonic transceiver. See, for example, Bertrand et al., Beamforming Approaches for Untethered, Ultrasonic Neural Dust Motes for Cortical Recording: a Simulation Study, IEEE EMBC (August 2014). In some embodiments, beam steering is performed by adjusting the power or phase of the ultrasonic waves emitted by the transducers in an array.
In some embodiments, the interrogator includes one or more of instructions for beam steering ultrasonic waves using one or more transducers, instructions for determining the relative location of one or more implantable devices, instructions for monitoring the relative movement of one or more implantable devices, instructions for recording the relative movement of one or more implantable devices, and instructions for deconvoluting backscatter from a plurality of implantable devices.
Optionally, the interrogator is controlled using a separate computer system, such as a mobile device (e.g., a smartphone or a tablet). The computer system can wirelessly communicate to the interrogator, for example through a network connection, a radiofrequency (RF) connection, or Bluetooth. The computer system may, for example, turn on or off the interrogator or analyze information encoded in ultrasonic waves received by the interrogator.
The implantable device and the interrogator wirelessly communicate with each other, for example using ultrasonic waves or radiofrequency waves. The communication may be a one-way communication (for example, the interrogator transmitting information to the implantable device, or the implantable device transmitting information to the interrogator), or a two-way communication (for example, the interrogator transmitting information to the implantable device, or the implantable device transmitting information to the interrogator). Information transmitted from the implantable device to the interrogator may rely on, for example, a backscatter communication protocol. For example, the interrogator may transmit ultrasonic or RF waves to the implantable device, which emits backscatter waves that encode the information. The interrogator can receive the backscatter waves and decipher the information encoded in the received backscatter waves.
In some embodiments, the implantable device receives ultrasonic or radiofrequency waves from the interrogator through one or more ultrasonic transducers or RF antennas on the implantable device, and the received waves can encode instructions for operating the implantable device. For example, vibrations of the ultrasonic transducer(s) on the implantable device generate a voltage across the electric terminals of the transducer, and current flows through the device, including the integrated circuit. The current (which may be generated, for example, using one or more ultrasonic transducers or RF antennas) can be used to charge an energy storage circuit, which can store energy to be used to emit an electrical pulse, for example after receiving a trigger signal. The trigger signal can be transmitted from the interrogator to the implantable device, signaling 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 decipher the trigger signal and operate the electrodes and electrical storage circuit to emit the pulse.
In some embodiments, ultrasonic backscatter or radiofrequency backscatter is emitted from the implantable device, which can encode information relating to the implantable device, the electrical pulse emitted by the implantable device, an electrophysiological pulse detected by the implantable device, or a detected physiological condition. For example, the backscatter can encode a verification signal, which verifies that electrical pulse was emitted. In some embodiments, an implantable device is configured to detect an electrophysiological signal, and information regarding the detected electrophysiological signal can be transmitted to the interrogator by the ultrasonic backscatter. To encode signals in the backscatter, current flowing through the ultrasonic transducer(s) of the implantable device is modulated as a function of the encoded information, such as a detected electrophysiological signal or measured physiological condition. In some embodiments, modulation of the current can be an analog signal, which may be, for example, directly modulated by the detected electrophysiological signal. In some embodiments, modulation of the current encodes a digitized signal, which may be controlled by a digital circuit in the integrated circuit. The backscatter is received by an external interrogator (which may be the same or different from the external interrogator that transmitted the initial ultrasonic waves). The information from the electrophysiological signal can thus be encoded by changes in amplitude, frequency, or phase of the backscattered ultrasound waves.
Communication between the interrogator and the implantable device can use a pulse-echo method of transmitting and receiving ultrasonic waves 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 pulses output can be two-level (GND and POS), three-level (GND, NEG, POS), 5-level, or any other multiple-level (for example, if using 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 a portion of the transducers on the interrogator are configured to receive ultrasonic waves and a portion of the transducers on the interrogator are configured to transmit ultrasonic waves. Transducers configured to receive ultrasonic waves and transducers configured to transmit ultrasonic waves can be on the same transducer array or on different transducer arrays of the interrogator. In some embodiments, a transducer on the interrogator can be configured to alternatively transmit or receive the ultrasonic waves. For example, a transducer can cycle between transmitting one or more pulses and a pause period. The transducer is configured to transmit the ultrasonic waves when transmitting the one or more pulses, and can then switch to a receiving mode during the pause period.
In some embodiments, the backscattered waves are digitized by the implantable device. For example, the implantable device can include an oscilloscope or analog-to-digital converter (ADC) and/or a memory, which can digitally encode information in current (or impedance) fluctuations. The digitized current fluctuations, which can encode information, are received by wireless communication system, which then transmits digitized ultrasonic or radiofrequency waves. The digitized data can compress the analog data, for example by using singular value decomposition (SVD) and least squares-based compression. In some embodiments, the compression is performed by a correlator or pattern detection algorithm. The backscatter signal may go through a series of non-linear transformation, such as 4th order Butterworth bandpass filter rectification integration of backscatter regions to generate a reconstruction data point at a single time instance. Such transformations can be done either in hardware (i.e., hard-coded) or in software.
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, the unique identifier can identify the implantable device of origin when from a plurality of implantable devices, for example when transmitting information from the implantable device (such as a verification signal). In some embodiments, an implantable device comprises a plurality of electrode pairs, which may simultaneously or alternatively emit an electrical pulse by a single implantable device. Different pairs of electrodes, for example, can be configured to emit an electrical pulse in different tissues (e.g., different nerves or different muscles) or in different regions of the same tissue. The digitized circuit can encode a unique identifier to identify and/or verify which electrode pairs emitted the electrical pulse.
In some embodiments, the digitized signal compresses the size of the analog signal. The decreased size of the digitized signal can allow for more efficient reporting of information encoded in the backscatter. By compressing the size of the transmitted information through digitization, potentially overlapping signals can be accurately transmitted.
In some embodiments, an interrogator communicates with a plurality of implantable devices. This can be performed, for example, using multiple-input, multiple output (MIMO) system theory. For example, communication between the interrogator and the plurality of implantable devices using time division multiplexing, spatial multiplexing, or frequency multiplexing. The interrogator can receive a combined backscatter from the plurality of the implantable devices, which can be deconvoluted, thereby extracting information from each implantable device. In some embodiments, interrogator focuses the ultrasonic waves transmitted from a transducer array to a particular implantable device through beamsteering. The interrogator focuses the transmitted ultrasonic waves to a first implantable device, receives backscatter from the first implantable device, focuses transmitted ultrasonic waves to a second implantable device, and receives backscatter from the second implantable device. In some embodiments, the interrogator transmits ultrasonic waves to a plurality of implantable devices, and then receives ultrasonic waves from the plurality of implantable devices.
The nerve cuff, or the implantable device comprising the nerve cuff, is implanted in a subject such that the helical nerve cuff at least partially wraps around a filamentous tissue comprising a nerve, which positions the electrodes of the device in electrical communication with the nerve. The nerve cuff or implantable device having the nerve cuff may be implanted in a surgical process using available surgical tools. Certain nerves or neurovascular bundles within a subject are limiting in space, and the implantation methods described herein may be beneficial for implanting the device or helical nerve cuff within a small surgical field.
The implantable device or helical nerve cuff may be implanted in the subject by at least partially unwinding the helical nerve cuff, passing an end of the helical nerve cuff behind a fibrous tissue comprising a nerve, and pulling the end of the helical nerve cuff that passed behind the fibrous tissue. Partially unwinding the helical nerve cuff configures the nerve cuff in a flexed state, and the nerve cuff may be released into a relax state, which wraps the helical nerve cuff around the fibrous tissue. The helical nerve cuff may be positioned once wrapped around the helical nerve cuff, for example by tucking the end of the helical nerve cuff under or behind the fibrous tissue.
The fibrous tissue may be isolated for implantation by separating the fibrous tissue from surrounding tissue, for example by circumferentially dissecting or partially circumferentially dissecting a portion of the fibrous tissue. An initial incision may be made to access the fibrous tissue, which may be overlaid by other tissue. Once the fibrous tissue is isolated, the implantable device or helical nerve cuff may be brought into the surgical field. The helical nerve cuff or implantable device may be oriented such that the axis of the helical nerve cuff is substantially parallel to the fibrous tissue. In this orientation, an end of the helical nerve cuff may be passed behind the fibrous tissue (for example from underneath the fibrous tissue).
The end of the helical nerve cuff may be initially threaded behind the fibrous tissue by pushing the end of the helical nerve cuff. A handle portion (e.g., a filament, suture, loop, etc.) may be attached to the end of the helical nerve cuff, which can be pulled to thread the helical nerve cuff behind the filamentous tissue.
In some embodiments, the helical nerve cuff is at least partially unwound prior to pulling the end of the helical nerve cuff passed behind the fibrous tissue. For example, a handle portion at one or both ends of the helical nerve cuff may be grasped and the helical nerve cuff manipulated to unwind the helix in a radial movement. Unwinding the helical nerve cuff configures the nerve cuff in a flexed configuration, and the nerve cuff can recoil in a relaxed configuration to rewind the helix. The end of the at least partially unwound helix can then be passed behind the fibrous tissue (which may include pulling on the end of the helical nerve cuff). Once the end is passed, the flexed helical nerve cuff may be released, which cases the helical nerve cuff to wrap around the fibrous tissue. The helical nerve cuff (and/or body, if present) can then be repositioned to ensure contact between the electrodes of the helical nerve cuff and the fibrous tissue.
In some embodiments, the helical nerve cuff is at least partially unwound by pulling the end of the helical nerve cuff passed behind the fibrous tissue. For example, the end of the helical nerve cuff may be passed behind the fibrous tissue with the helical nerve cuff in a relaxed configuration (i.e., a wound helix). The end of the helical nerve cuff passed behind the fibrous tissue can then be pulled (for example, by pulling a handle portion attached to the end of the helical nerve cuff). Pulling the end of the helical nerve cuff causes the nerve cuff to partially unwind as it is passed behind the filamentous tissue. The helical nerve cuff (and/or body, if present) can then be repositioned to ensure contact between the electrodes of the helical nerve cuff and the fibrous tissue.
The body of the implantable device may be attached to a first end of the helical nerve cuff or the middle of the helical nerve cuff, leaving the second end of the helical nerve cuff configured to pass behind the fibrous tissue. Optionally, the body may be held in an approximately steady position as the end of the helical nerve cuff is passed behind the fibrous tissue. 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 grasped to stabilize the body. There may be some slight movement of the body, but movement of the body can be limited to avoid the body catching on surrounding tissue or the fibrous tissue when the helical nerve cuff is passed behind the fibrous tissue. Nevertheless, in some embodiments, the body of the implantable device is unrestrained, and may freely move as the helical nerve cuff is passed behind the fibrous tissue.
Once the helical nerve cuff of an implantable devices is wrapped around the filamentous tissue, the body of the implantable device may be positioned in the desired orientation. For example, if the body includes an acoustic window, the acoustic window of the body can be oriented in a direction of a desired interrogator position.
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 a rodent (such as a rat or mouse). The helical nerve cuff may implanted such that it at least partially wrap around a filamentous tissue (such as a peripheral nerve, or a filamentous tissue comprising a peripheral nerve, such as a neurovascular bundle) within any of these animals, or others. For example, in some embodiments, the helical nerve cuff or implantable device is implanted such that the nerve cuff at least partially wrap around a human peripheral nerve, such as a human splenic nerve, or a human splenic neurovascular bundle. In some embodiments, the helical nerve cuff or implantable device is implanted such that the nerve cuff at least partially wrap around an autonomic nerve. In some embodiments, the nerve is a sympathetic nerve. In some embodiments, the nerve is a vagus nerve, a mesenteric nerve, a splenic nerve, a sciatic nerve, a tibial nerve, a pudendal nerve, a celiac ganglion, a sacral nerve, or any branch thereof.
The implantable device can be made by attaching a device body to a helical nerve cuff, or by assembling the helical nerve cuff on the device body. For example, the helical nerve cuff may comprise two or more substrate layers, and a first substrate layer may be attached to the device body before a second substrate layer is attached to the first substrate layer, thus forming the helical nerve cuff.
At step 1802, a feedthrough is attached to a housing. The housing can include a feedthrough port, for example on the bottom of the housing, which is configured to receive the feedthrough. The feedthrough may then be attached to the housing at the feedthrough port, for example by welding or braising the feedthrough to the housing. Attaching the feedthrough to the feedthrough port of the housing can create a seal at the feedthrough port.
At step 1804, a board assembly is positioned within the housing. The board assembly may 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 may be attached to a flex board, for example by using a conductive adhesive and/or wirebonding the components to form the board assembly. The board assembly is positioned within the housing to electrically connect the feedthrough to the board assembly. Alternatively, the feedthrough may be attached to the board assembly before the board assembly is positioned in the housing, and the feedthrough can then be attached to the housing once the board assembly is in place.
At step 1806, an open portion of the housing is closed with a lid, for example an acoustic window. The board assembly may be positioned in the housing, for example, through the open portion. The lid may include an acoustic window. For example, if the wireless communication system of the board assembly includes one or more ultrasonic transducers, an acoustic window can be included to allow ultrasonic waves to penetrate the housing. An acoustic window may be formed, for example, by attaching a foil to a frame (for example by diffusion bonding the foil to the frame). Then, the acoustic window may be attached to the open housing, for example by laser welding.
At step 1808, an acoustically conductive material is filled into the housing. This step is optional, and may not be applicable for example if the wireless communication system is not an acoustically-based communication system. However, if the wireless communication system includes one or more ultrasonic transducers, filling the housing with an acoustically conductive material can allow for better communication using ultrasonic waves. The acoustically conductive material may be filled in the housing using a port, which may be included on the side of the housing. A vacuum may optionally be used to ensure no bubbles are present in the acoustically conductive material. Once the housing is filled, the port can be sealed, for example by placing a plug in the port, which may be soldered or laser welded to seal the plug is position.
Once assembled, the housing is preferably hermetically sealed (for example, by sealing any housing opening, such as an open housing top, the feedthrough port and/or the acoustically conductive material port).
At step 1810, a first substrate layer for the nerve cuff is formed. The first nerve cuff layer may be molded or cut into a helical shape. A feedthrough port may also be cut or molded into the first nerve cuff layer, which is configured to allow the feedthrough attached to the housing to pass through the feedthrough port of the first layer.
At 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 feedthrough attached to the housing passes through the feedthrough port of the first substrate layer. The housing may be positioned as desired relative to the helical axis, such as parallel to or perpendicular to the helical axis. An adhesive and/or one or more fasteners may be used to secure the housing to the first substrate layer. For example, the housing may have one or more fasteners attached (e.g., soldered, welded, of formed form the housing), which can be passed through the first substrate and manipulated to secure the housing to the first layer.
At step 1814, the second substrate layer (e.g., the inner layer) is formed. One or more electrodes may be shaped (for example, by laser cutting an electrically conductive material), and then embedded in a second substrate material. If needed, flashing may be removed from the second substrate material to ensure the desired expos
At step 1816, the second substrate layer is attached to the first substrate layer. The second substrate layer may be aligned with the first substrate layer to align the feedthrough with the electrodes, thereby electrically connecting the electrodes to the board assembly through the feedthrough. The electrodes may be attached to the feedthrough, for example by soldering the feedthrough to the electrodes and/or using an adhesive. An adhesive may then be used to attach the second substrate layer to the first substrate layer, thereby forming the helical nerve cuff. Optionally, the second substrate layer is wrapped around a mandrel, and the first substrate layer may be 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 the 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.
The following embodiments are exemplary and are not intended to limit the scope of the present application:
Embodiment 1. An implantable device, comprising:
Embodiment 2. The implantable device of embodiment 1, wherein the wireless communication system comprises an ultrasonic transducer.
Embodiment 3. The implantable device of embodiment 2, wherein the ultrasonic transducer is about 5 mm or less in length in the longest dimension.
Embodiment 4. The implantable device of embodiment 2 or 3, wherein the wireless communication system comprises two or more ultrasonic transducers.
Embodiment 5. The implantable device of embodiment 1, wherein the wireless communication system comprises a radiofrequency antenna.
Embodiment 6. The implantable device of any one of embodiments 1-5, wherein the wireless communication system is configured to receive ultrasonic waves or radiofrequency waves, and convert energy from the ultrasonic waves or radiofrequency waves into an electrical energy that powers the device.
Embodiment 7. The implantable device of any one of embodiments 1-6, wherein the helical nerve cuff is configured to wrap around the nerve by at least one revolution.
Embodiment 8. The implantable device of embodiment 7, wherein the helical nerve cuff is configured to wrap around the nerve by about 1.3 to about 1.7 revolutions.
Embodiment 9. The implantable device of any one of embodiments 1-8, wherein the helical nerve cuff has a width that defines an inner surface, a first edge, and a second edges of the helical nerve cuff, and wherein at least a portion of the first edge contacts at least a portion of the second edge when the helical nerve cuff is in a relaxed position.
Embodiment 10. The implantable device of any one of embodiments 1-8, wherein the helical nerve cuff has a width that defines an inner surface, a first edge, and a second edges of the helical nerve cuff, and wherein the first edge does not contact the second edge when the helical nerve cuff is in a relaxed position.
Embodiment 11. The implantable device of any one of embodiments 1-10, wherein at least one of the two or more electrodes is positioned along the length of the helical nerve cuff.
Embodiment 12. The implantable device of embodiment 11, wherein the at least one of the two or more electrodes positioned along the length of the helical nerve cuff is positioned on an inner surface of the helical nerve cuff.
Embodiment 13. The implantable device of any one of embodiments 1-12, wherein the at least one electrode on the helical nerve cuff comprises one or more serpentine segments.
Embodiment 14. The implantable device of any one of embodiments 1-13, wherein the helical nerve cuff is flexible and is configurable in (a) a flexed position by at least partially unwinding the helical nerve cuff, and (b) a relaxed position.
Embodiment 15. The implantable device of any one of embodiments 1-14, further comprising a handle portion attached the helical nerve cuff or the body.
Embodiment 16. The implantable device of embodiment 15, wherein the handle portion comprises a loop.
Embodiment 17. The implantable device of embodiment 15 or 16, wherein the handle portion comprises a filament.
Embodiment 18. The implantable device of any one of embodiments 15-17, wherein the handle portion is attached to the nerve cuff at a position proximal to an end of the helical nerve cuff.
Embodiment 19. The implantable device of embodiment 18, further comprising a second handle portion attached to the helical nerve cuff at a position proximal to a second end of the helical nerve cuff.
Embodiment 20. The implantable device of embodiment 19, wherein the first handle portion is attached to the second handle.
Embodiment 21. The implantable device of any one of embodiments 16-20, further comprising an additional handle portion attached to a middle position along the length of the helical nerve cuff.
Embodiment 22. The implantable device of any one of embodiments 1-21, further comprising a mount configured to receive the body and the helical nerve cuff, thereby attaching the body on the helical nerve cuff.
Embodiment 23. The implantable device of any one of embodiments 1-21, wherein the body is directly attached on an outer surface of the helical nerve cuff.
Embodiment 24. The implantable device of any one of embodiments 1-23, wherein the body is attached to an end of the helical nerve cuff.
Embodiment 25. The implantable device any one of embodiments 1-23, wherein the body is attached to middle portion of the helical nerve cuff.
Embodiment 26. The implantable device of any one of embodiments 1-25, wherein the body comprises an attachment end attached to the helical nerve cuff and an extension end extending from the attachment end.
Embodiment 27. The implantable device of any one of embodiments 1-26, wherein the helical nerve cuff comprises a right-handed helical portion.
Embodiment 28. The implantable device of any one of embodiments 1-26, wherein the helical nerve cuff comprises a left-handed helical portion.
Embodiment 29. The implantable device of any one of embodiments 1-28, wherein the helical nerve cuff comprises a right-handed helical portion joined to a left-handed helical portion.
Embodiment 30. The implantable device of embodiment 29, wherein the body attaches to the helical nerve cuff at a position proximal to where the right-handed helix portion is joined to the left-handed helical portion.
Embodiment 31. The implantable device of embodiment 29 or 30, wherein the right-handed helical portion is joined to a left-handed helical portion through a linear joining portion.
Embodiment 32. The implantable device of any one of embodiments 1-31, wherein the helical nerve cuff comprises one or more electrodes configured to emit an electrical pulse to the nerve.
Embodiment 33. The implantable device of anyone of embodiments 1-32, wherein the helical nerve cuff comprises one or more electrodes configured to detect the electrophysiological signal transmitted by the nerve.
Embodiment 34. The implantable device of embodiments 33, wherein the helical nerve cuff comprises two or more electrodes configured to detect the electrophysiological signal transmitted by the nerve.
Embodiment 35A. The implantable device of any one of embodiments 1-34, wherein the nerve is a human splenic nerve.
Embodiment 35B. The implantable device of any one of embodiments 1-34, wherein the nerve is a human splanchnic nerve.
Embodiment 36. The implantable device of any one of embodiments 1-35A and 35B, wherein the body comprises a housing.
Embodiment 37. The implantable device of embodiment 36, wherein the housing is configured as one of the two or more electrodes.
Embodiment 38. The implantable device of embodiment 36 or 37, wherein the housing comprises an acoustic window.
Embodiment 39. The implantable device of any one of embodiments 36-38, wherein the housing contains an acoustically conductive material.
Embodiment 40. The implantable device of any one of embodiments 1-39, wherein the body comprises an integrated circuit electrically connected to the wireless communication system and the two or more electrodes.
Embodiment 41. The implantable device of embodiment 40, wherein the integrated circuit comprises an energy storage circuit comprising a capacitor.
Embodiment 42. The implantable device of any one of embodiments 1-41, wherein the body is about 8 mm or less in length in the longest dimension.
Embodiment 43. The implantable device of any one of embodiments 1-42, wherein the wireless communication system is configured to transmit data.
Embodiment 44. The implantable device of embodiment 43, wherein the wireless communication system is configured to emit an ultrasonic backscatter or radiofrequency backscatter that encodes the data.
Embodiment 45. The implantable device of embodiment 43 or 44, wherein the data comprises information related to a detected electrophysiological signal, a measured physiological condition, a device status, or an emitted electrical pulse.
Embodiment 46. The implantable device of any one of embodiments 1-45, wherein the wireless communication system is configured to receive instructions for operating the implantable device.
Embodiment 47. The implantable device of embodiment 46, wherein the instructions are encoded in ultrasonic waves or radiofrequency waves.
Embodiment 48. The implantable device of embodiment 46 or 47, wherein the instructions comprise a trigger signal that operates the implantable device to emit an electrical pulse to the nerve.
Embodiment 49. The implantable device of any one of embodiments 1-48, wherein the implantable device further comprises a sensor configured to detect a physiological condition.
Embodiment 50. The implantable device of embodiment 49, wherein the sensor is configured to detect temperature. pH, pressure, strain, or an analyte concentration.
Embodiment 51. The implantable device of any one of embodiments 1-50, wherein the fibrous tissue comprises a blood vessel.
Embodiment 52. A system, comprising the implantable device of any one of embodiments 1-51, and an interrogator comprising a second wireless communication system configured to wirelessly communicate with the wireless communication system of the implantable device.
Embodiment 53. The system of embodiments 52, wherein the second wireless communication system comprises one or more ultrasonic transducers configured to transmit ultrasonic waves to the implantable medical device, wherein the ultrasonic waves power the implantable medical device.
Embodiment 54. The system of embodiment 52, wherein the second wireless communication system comprises one or more radiofrequency antennas configured to transmit radiofrequency waves to the implantable medical device, wherein the radiofrequency waves power the implantable medical device.
Embodiment 55. The system of any one of embodiments 52-54, wherein the interrogator is configured to be worn externally.
Embodiment 56. A nerve cuff, comprising:
Embodiment 57. The nerve cuff of embodiment 56, wherein the handle portion comprises a loop.
Embodiment 58. The nerve cuff of embodiment 56 or 57, wherein the handle portion comprises a filament.
Embodiment 59. The nerve cuff of any one of embodiments 56-58, wherein the helical nerve cuff is configured to wrap around the nerve by at least one revolution.
Embodiment 60. The nerve cuff of embodiment 59, wherein the helical nerve cuff is configured to wrap around the nerve by about 1.3 to about 1.7 revolutions.
Embodiment 61. The nerve cuff of any one of embodiments 56-60, wherein a portion of the handle portion is embedded within the substrate.
Embodiment 62. The nerve cuff of any one of embodiments 56-61, wherein the handle portion is attached to the nerve cuff at a position proximal to an end of the helical nerve cuff.
Embodiment 63. The nerve cuff of embodiment 62, further comprising a second handle portion attached to the helical nerve cuff at a position proximal to a second end of the helical nerve cuff.
Embodiment 64. The nerve cuff of embodiment 63, wherein the first handle portion and the second handle portion are separated by a radial angle of about 90° to about 180° around a helical axis.
Embodiment 65. The nerve cuff of embodiment 63 or 64, wherein the first handle portion is attached to the second handle portion.
Embodiment 66. The implantable device of any one of embodiments 56-65, further comprising an additional handle portion attached to a middle position along the length of the helical nerve cuff.
Embodiment 67. The nerve cuff of any one of embodiments 56-66, wherein the substrate has a width that defines an inner surface, a first edge of the substrate, and a second edge of the substrate, and wherein at least a portion of the first edge contacts at least a portion of the second edge when the nerve cuff is in a relaxed position.
Embodiment 68. The nerve cuff of any one of embodiments 56-66, wherein the substrate has a width that defines an inner surface, a first edge of the substrate, and a second edge of the substrate, and wherein the first edge does not contact the second edge when the nerve cuff is in a relaxed position.
Embodiment 69. The nerve cuff of any one of embodiments 56-68, wherein the at least one of the one or more electrodes is positioned along the length of the helical nerve cuff.
Embodiment 70. The nerve cuff of embodiment 69, wherein the at least one of the one or more electrodes positioned along the length of the helical nerve cuff is positioned on an inner surface of the helical nerve cuff.
Embodiment 71. The nerve cuff of any one of embodiments 56-70, wherein the at least one of the one or more electrodes comprises one or more serpentine segments.
Embodiment 72. The nerve cuff of any one of embodiments 56-71, wherein the helical nerve cuff is configured to be unwound by at least one revolution.
Embodiment 73. The nerve cuff of any one of embodiments 56-72, wherein the helical nerve cuff comprises a right-handed helical portion.
Embodiment 74. The nerve cuff of any one of embodiments 56-72, wherein the helical nerve cuff comprises a left-handed helical portion.
Embodiment 75. The nerve cuff of any one of embodiments 56-73, wherein the helical nerve cuff comprises a right-handed helical portion joined to a left-handed helical portion.
Embodiment 76. The nerve cuff of any one of embodiments 56-75, comprising a first helical portion joined to a second helical portion through a linear connecting member.
Embodiment 77. The nerve cuff of any one of embodiments 56-76, wherein the nerve cuff comprises one or more electrodes configured to emit an electrical pulse to the nerve.
Embodiment 78. The nerve cuff of anyone of embodiments 56-77, wherein the nerve cuff comprises one or more electrodes configured to detect the electrophysiological signal transmitted by the nerve.
Embodiment 79. The nerve cuff of embodiments 78, wherein the nerve cuff comprises two or more electrodes configured to detect the electrophysiological signal transmitted by the nerve.
Embodiment 80. The nerve cuff of any one of embodiments 56-79, wherein the nerve cuff comprises one or more electrodes configured to detect the electrophysiological signal transmitted by the nerve, and one or more electrodes configured to emit an electrical pulse to the nerve, wherein at least one of the one or more electrodes configured to emit an electrical pulse to the nerve is wider than at least one of the one or more electrodes configured to detect the electrophysiological signal transmitted by the nerve.
Embodiment 81. The nerve cuff of any one of embodiments 56-80, further comprising a mount attached to the helical substrate configured to receive a body and electrically connect the one or more electrodes positioned along the length of the helical substrate to the body.
Embodiment 82. The nerve cuff of embodiment 81, wherein the body directly connects with the one or more electrodes.
Embodiment 83. The nerve cuff of embodiment 81, wherein the mount comprises one or more feedthroughs configured to electrically connect the body to the one or more electrodes.
Embodiment 84A. The nerve cuff of any one of embodiments 56-83, wherein the nerve is a splenic nerve.
Embodiment 84B. The nerve cuff of any one of embodiments 56-83, wherein the nerve is a splanchnic nerve.
Embodiment 85. A method of implanting a helical nerve cuff comprising one or more electrodes, comprising:
Embodiment 86. The method of embodiment 85, wherein the helical nerve cuff is the nerve cuff of any one of embodiments 56-84A and 84B.
Embodiment 87. A method of implanting an implantable device comprising a body comprising a wireless communication system on a helical nerve cuff comprising one or more electrodes, the method comprising:
Embodiment 88. The method of embodiment 87, comprising limiting movement of the body as the end of the helical nerve cuff is passed behind the fibrous tissue.
Embodiment 89. The method of embodiment 88, wherein the body is held in an approximately steady position by holding a handle portion attached to the helical nerve cuff at a position proximal to the body or a handle portion attached to the body.
Embodiment 90. The method of any one of embodiments 87-89, wherein the implantable device is the implantable device of any one of embodiments 1-51.
Embodiment 91. The method of any one of embodiments 85-90, comprising pulling the end of the helical nerve cuff passed behind the fibrous tissue.
Embodiment 92. The method of any one of embodiments 85-91, comprising orienting the helical nerve cuff substantially parallel to the fibrous tissue.
Embodiment 93. The method of any one of embodiments 85-92, wherein the helical nerve cuff is at least partially unwound by pulling the end of the helical nerve cuff passed behind the fibrous tissue.
Embodiment 94. The method of any one of embodiments 85-92, wherein the helical nerve cuff is at least partially unwound prior to pulling the end of the helical nerve cuff passed behind the fibrous tissue.
Embodiment 95. The method of any one of embodiments 85-94, wherein the end of the helical nerve cuff is passed behind the fibrous tissue from underneath the fibrous tissue.
Embodiment 96. The method of any one of embodiments 85-95, further comprising separating the fibrous tissue from surrounding tissue.
Embodiment 97. The method of embodiment 96, wherein the fibrous tissue is separated from the surrounding tissue by circumferentially dissecting a portion of the fibrous tissue.
Embodiment 98. The method of any one of embodiment 85-97, wherein the end of the helical nerve cuff passed behind the fibrous tissue is pulled by pulling a handle portion attached to the end of the helical nerve cuff.
Embodiment 99A. The method of any one of embodiments 85-98, wherein the fibrous tissue comprises a splenic nerve.
Embodiment 99B. The method of any one of embodiments 85-98, wherein the fibrous tissue comprises a splanchnic nerve.
Embodiment 100. A method of making an implantable device, comprising:
Embodiment 101. The method of embodiment 100, wherein the feedthrough is attached to the housing prior to board assembly being positioned into the housing.
Embodiment 102. The method of embodiment 100, wherein the feedthrough is attached to the board assembly before the board assembly is positioned into the housing.
Embodiment 103. The method of any one of embodiments 100-102, comprising sealing the housing.
Embodiment 104. The method of any one of embodiments 100-103, comprising attaching an acoustic window to the housing.
Embodiment 105. The method of embodiment 104, wherein the acoustic window is attached to an open top of the housing after the board assembly is positioned within the housing.
Embodiment 106. The method of embodiment 104 or 105, comprising assembling the acoustic window by attaching a foil to a frame.
Embodiment 107. The method of any one of embodiments 100-106, comprising filling the housing with an acoustically conductive material.
Embodiment 108. The method of embodiment 107, wherein the acoustically conductive material is filled into the housing through a port on the housing, the method comprising sealing the port.
Embodiment 109. The method of any one of embodiments 100-108, comprising attaching the wireless communication system to the board assembly.
Embodiment 110. The method of any one of embodiments 100-109, wherein the wireless communication system comprises one or more ultrasonic transducers.
Embodiment 111. The method of any one of embodiments 100-110, wherein the board assembly comprises an integrated circuit electrically connected to the wireless communication system.
Embodiment 112. The method of any one of embodiments 100-111, wherein the housing is directly attached to the first nerve cuff layer.
Embodiment 113. The method of any one of embodiments 100-112, wherein an adhesive or a fastener is used to attach the housing to the first nerve cuff layer.
Embodiment 114. The method of any one of embodiments 100-113, wherein the first nerve cuff layer is helical.
Embodiment 115. The method of any one of embodiments 100-114, comprising 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.
Embodiment 116. The method of any one of embodiments 100-115, comprising making the second nerve cuff layer by embedding one or more electrodes in a substrate material.
Embodiment 117. The method of any one of embodiments 100-116, comprising wrapping the second nerve cuff layer around a mandrel, and attaching the second nerve cuff layer to the first nerve cuff layer while the second nerve cuff layer is wrapped around the mandrel.
This application claims the priority benefit to U.S. Provisional Application No. 62/916,709, filed on Oct. 17, 2019, which is incorporated herein by reference for all purposes.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US2020/056161 | 10/16/2020 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 62916709 | Oct 2019 | US |
