Systems and methods for neurostimulation

Abstract

A method of stimulating nerves by providing a device having arms formed of an elastomeric material. A passage through which nerves pass is at least partially defined by the arms. The channel has a continuous axial longitudinal axis when resting. The neurostimulation chamber is at least partially defined by the arm. The nerve stimulation chamber is configured to retain a nerve therein. The device has an electrode within the chamber. The method reduces the size of the nerve. And the diameter is less than 50% of the undeformed nerve diameter. The device is configured such that the pressure applied to the nerve at any given point is less than 6.7 kPa. The nerve is placed in the room, and the cross section size of the stretched nerve is increased. At least 20% of the nerve perimeter remains in contact with the electrodes.

Description

[0001] priority

[0002] This patent application claims priority to U.S. Provisional Patent Application Nos. 63 / 391,574 and 63 / 391,584, filed on July 22, 2022, the disclosures of both applications are incorporated herein by reference in their entirety. Technical Field

[0003] Exemplary embodiments of the present invention relate generally to pelvic organ function, and more particularly, various embodiments of the present invention relate to selective neuromodulation for controlling bladder and pelvic floor function. Background Art

[0004] Millions of people in the United States and around the world suffer from overactive bladder ("OAB"), a condition that can cause debilitating urinary urgency and frequency, with or without urinary incontinence. Confounding many in the art, OAB is associated with nocturia, but in the absence of urinary tract infection or other overt pathology. The pathophysiology and etiology of idiopathic OAB are unclear, but appear to be related to bladder detrusor dysfunction or detrusor overactivity. Current drug treatments include oral antimuscarinics or oral β3-adrenergic receptor agonists. These treatments have significant disadvantages in that they have limited efficacy and tolerability, resulting in significant side effects, including dry mouth, dry eyes, constipation, tachycardia, and potential long-term cognitive effects. As a result, studies have shown that most OAB patients stop taking these medications within 6 to 12 months of treatment.

[0005] Another urinary problem is called "stress urinary incontinence" ("SUI"), which occurs when sudden pressure is put on the bladder and urethra, causing the sphincter muscle to briefly open, causing urine to leak out. With mild SUI, the pressure may come from sudden, intense activity, such as moderate exercise, sneezing, laughing, or coughing. However, if SUI is more severe, urine may leak during less strenuous activities such as standing, walking, or bending. Urine "accidents" like these can range from a few drops of urine to enough to soak through clothing.

[0006] Those skilled in the art generally use different treatment regimens to treat OAB and SUI. Summary of the invention

[0007] According to one embodiment, a neuromodulatory device includes a body including an airtight sealed housing containing electronics therein. The body has a buffer layer that at least partially encapsulates the airtight sealed housing. A movable arm is coupled to the body. The movable arm is configured to transition between an open configuration and a closed configuration. The movable arm is biased toward the closed configuration. A neurostimulation chamber is at least partially defined by the movable arm. The neurostimulation chamber is configured to retain a nerve therein. The size and shape of the chamber are adjusted by movement of the arm in response to contact with the nerve. The device has an open channel through which the nerve travels. The channel is at least partially defined by the movable arm. The size and shape of the channel are adjusted by movement of the arm in response to contact with the nerve. When the movable arm is in the closed configuration, the channel can extend continuously axially along the longitudinal axis of the channel. The chamber has an electrode.

[0008] Some embodiments include a second arm. The second arm can be configured to transition between an open configuration and a closed configuration. The second arm can be biased toward the closed configuration. Movement of the second movable arm can adjust the size of the chamber and / or the size of the channel. When the movable arm is biased toward the closed configuration, the movable arm can be configured to non-invasively retain a nerve having a resting maximum cross-sectional dimension of 0.5 mm to 4 mm in the chamber.

[0009] Among other things, the chamber may contain one or more nerve release spaces defined by the movable arm. The movable arm may also contain one or more bending points. The distal end of the electrode may be embedded in the movable arm. A continuous feedthrough electrical wire may extend through the hermetically sealed housing to form the electrode.

[0010] In various embodiments, the channel is non-linear. The chamber can be configured such that the electrode is curved and has a size that contacts at least 20% of the circumference of a nerve having a maximum cross-sectional dimension of 0.5 mm to 4 mm. The channel can be non-linear and extend continuously axially.

[0011] According to another embodiment, a method for stimulating a nerve provides a neuromodulatory device. The device has a body, which includes an airtight sealed housing containing electronic devices, and a buffer layer that at least partially encapsulates the airtight sealed housing. A movable arm is coupled to the body. The movable arm is configured to switch between an open configuration and a closed configuration. The movable arm is biased toward the closed configuration. The nerve stimulation chamber is at least partially defined by the movable arm. The nerve stimulation chamber is configured to hold the nerve therein. The size and shape of the chamber are adjustable by movement of the arm. The channel through which the nerve passes is at least partially defined by the movable arm. The size and shape of the channel are adjustable by movement of the arm. The channel extends continuously axially along the longitudinal axis of the channel. The device may include electrodes located within the chamber. The method reduces the maximum cross-sectional dimension of the nerve to define a stretched nerve with a reduced cross-sectional dimension. The stretched nerve moves in the channel along the central axis of the channel. The nerve is placed in the chamber, and the cross-sectional dimension of the stretched nerve increases.

[0012] In various embodiments, electrodes are used to stimulate nerves. Various control signals are used to control stimulation parameters.

[0013] According to another embodiment, a method stimulates a nerve. The method provides a device having a body including an airtight sealed housing containing electronic devices therein. The device has an arm formed of an elastic material. A channel through which the nerve passes is at least partially defined by the arm. The channel has a continuous axial longitudinal axis when at rest. A nerve stimulation chamber is at least partially defined by the arm. The nerve stimulation chamber is configured to hold the nerve therein. The device has an electrode in the chamber. The method reduces the maximum cross-sectional dimension of the nerve to define a stretched nerve having a reduced cross-sectional dimension. The reduction in the maximum cross-sectional dimension is less than 50% of the diameter of the undeformed nerve. The stretched nerve passes through the channel along a central axis so that the pressure exerted on the nerve by the wall of the channel at any given point is less than 6.7 kPa. The nerve is placed in the chamber and the cross-sectional dimension of the stretched nerve increases. At least 20% of the circumference of the nerve is in contact with the electrode.

[0014] In various embodiments, the nerve can have a different cross-sectional shape while in the chamber, but the cross-sectional area can be substantially the same as the undeformed nerve.

[0015] Some embodiments can reduce the cross-sectional dimension of the nerve in the chamber to define a stretched nerve having a second reduced cross-sectional dimension. The reduction in the maximum cross-sectional dimension can be less than 50% of the maximum cross-sectional dimension. The stretched nerve can be passed through the channel along the central axis to remove the nerve from the device such that the pressure exerted on the nerve by the channel wall is less than 6.7 kPa.

[0016] Various embodiments can maintain at least 20% of the circumference of the nerve in contact with the electrode while providing a holding pressure of less than 4 kPa to the nerve. The undeformed diameter of the nerve can be between 0.5 mm and 4 mm. The cross-sectional area of ​​the nerve placed in the chamber can be greater than 50% of the cross-sectional area of ​​the undeformed nerve. In some embodiments, the cross-sectional area of ​​the nerve in the chamber can be equal to the cross-sectional area of ​​the undeformed nerve. To this end, the chamber can include a nerve relief space.

[0017] The arms may be movable between an open configuration and a closed configuration. The arms may be biased toward the closed configuration such that the size of the chamber and / or channel may be adjustable by movement of the arms. The arms may have one or more bends such that the size of the chamber may be adjusted by bending of the arms. The arms may include a cushioning material configured to deform when a pressure is less than 6.7 kPa such that the size of the chamber and / or channel may be adjustable by deformation of the arms. One or more arms may form a continuous axial channel through which a nerve passes. The channel may be defined at least in part by the arms. The channel may be nonlinear along its central axis.

[0018] In various embodiments, the buffer layer may be formed of silicone. The package body may be formed of glass, ceramic, alumina, zirconium and / or plastic. A continuous feed-through conductor may extend through the package, the buffer layer and through the movable arm. The feed-through conductor may form an electrode. Thus, the electrode may advantageously not be welded / joined.

[0019] According to another embodiment, the movable arm is formed of an elastic material. The movable arm is configured to transition between an open configuration and a closed configuration. The movable arm is biased toward the closed configuration. The movable arm at least partially defines the chamber and the channel. The gap of the movable arm is less than 1 mm. The movable arm is configured to allow a nerve having a diameter between 1 mm and 3 mm to pass through the channel while providing a pressure of less than 6.7 kPa to the nerve. The movable arm is also configured to provide a pressure of less than 4 kPa to the nerve when the electrode in the chamber stimulates the nerve.

[0020] The movable arm can be configured to compress the nerve within the chamber to deform the nerve, but the cross-sectional area of ​​the nerve is reduced by no more than 10%.

[0021] According to one embodiment, a method controls bladder function of a patient having symptoms (e.g., associated with overactive bladder (OAB) or stress urinary incontinence (SUI)) that are associated with symptom signals (e.g., OAB signals) generated by the patient's body. The method provides a neuromodulatory device. The neuromodulatory device has a body and a movable arm. A channel is defined by the body and the movable arm. The channel leads from the outside of the neuromodulatory device to a stimulation chamber having stimulation electrodes therein. The movable arm transitions between a closed position and an open position. The movable arm is placed in the open position. After the movable arm is placed in the open position, a designated somatic motor nerve of the coccygeal plexus and / or perineal plexus associated with the pelvic floor is placed in the chamber. After the designated somatic motor nerve is placed in the chamber, the movable arm is placed in the closed position. The method transmits a symptom control signal (e.g., a SUI and / or OAB control signal) to the designated somatic motor nerve via an electrode. The control signal is configured to activate the pelvic floor in a designated manner to reduce the effects of the symptom signal on the spinal cord.

[0022] In some embodiments, a designated somatic nerve is positioned within the chamber and in contact with the electrode. Placing the movable arm in a closed position can compress the designated somatic nerve within the chamber, slightly deforming it without causing harm. For example, the nerve can be compressed by 30% without causing harm. In some embodiments, the nerve can be compressed by 50% without causing harm. The housing can include a protrusion configured to press against the movable arm when the movable arm is in the closed position. The protrusion can be configured to limit the amount of compression of the nerve by the movable arm.

[0023] In various embodiments, the electrode partially surrounds the nerve. The contact angle of the electrode to the circumference of the nerve can be less than 180 degrees. The movable arm can be biased toward a closed position. The designated somatic motor nerve includes the perineal nerve, further wherein the perineal nerve or pelvic floor nerve is part of the coccygeal plexus and / or the perineal plexus.

[0024] In some embodiments, the transmission includes generating a symptom control signal using a signal generator and transmitting the symptom control signal through an electrode. The symptom control signal can be transmitted using one or more wired or wireless communication media. The amplitude of the symptom control signal can be about 0.4 mA to 4 mA. The symptom control signal can be a periodic signal having a plurality of pulses, each having a pulse duration of about 200 microseconds to 400 microseconds. The symptom control signal can be a periodic signal having a frequency of about 5 Hz to 20 Hz. In a single session, the transmission time of the symptom control signal can be no less than 10 minutes and no more than 30 minutes.

[0025] Some embodiments may transmit the SUI control signal to a designated somatic motor nerve via an electrode. The frequency of the SUI control signal may be different from the frequency of the OAB control signal. The SUI control signal may be transmitted after the OAB control signal. The SUI control signal may be configured to enhance the pelvic floor when applied via a designated somatic motor nerve. The SUI control signal may be configured to enhance or repair the pelvic floor.

[0026] According to another embodiment, a system controls bladder function of a patient having a symptom (e.g., associated with overactive bladder (OAB) or stress urinary incontinence (SUI)). The symptom is associated with a symptom signal generated by the patient's body. The system includes a body coupled to a movable arm. The body and the movable arm define a channel therebetween. The channel leads from the outside of the body to a stimulation chamber. The movable arm is switchable between a closed position and an open position. The channel has a gap, the depth of which is greater in the open position than in the closed position. The system includes an electrode placed in the chamber. The electrode is configured to couple with a perineal nerve. The electrode has a receiving interface configured to receive an OAB control signal for actuating the perineal nerve. The gap depth in the closed position is configured to be less than about 100 μm to inhibit the perineal nerve from non-destructively entering the chamber. The gap depth in the open position is configured to be large enough (e.g., about 0.5 mm to 2.5 mm) to allow a nerve (e.g., a perineal nerve) to pass through. In various embodiments, the gap depth of the open position is configured to be large enough (eg, between about 0.5 mm and 2.5 mm) to allow the perineal nerve to pass through.

[0027] In some embodiments, the gap depth in the closed position is substantially zero. The system may also include a signal generator having a transmit interface configured to communicate with the receive interface of the electrode. The signal generator may be configured to send an OAB control signal to the electrode via the transmit interface and the receive interface. The OAB control signal may have a set of specified specifications to activate the pelvic floor in a specified manner, thereby mitigating the effects of the natural OAB signal on the pelvic floor.

[0028] In various embodiments, the electrode and the signal generator comprise components of the kit. The signal generator may have a memory for storing a specified specification group. The specified specification group may include an amplitude between about 0.4 mA and 4 mA. The specified specification group may include an OAB control signal, which is a periodic signal with multiple pulses. The pulse duration of each pulse is about 200 microseconds to 400 microseconds. The specified specification group may include an OAB control signal, which may have a periodic signal with a frequency of about 5 Hz to 20 Hz. The specified specification group may include a time frame for transmitting the OAB control signal. The duration of the time frame in a single connection may be no less than 10 minutes and no more than 30 minutes.

[0029] The signal generator may be configured to transmit a SUI control signal to the perineal nerve. The frequency of the SUI control signal may be different from the frequency of the OAB control signal. The signal generator may be configured to transmit the SUI control signal after the OAB control signal. The SUI control signal may be configured to enhance the pelvic floor when applied through the electrode and the perineal nerve.

[0030] The exemplary embodiments of the present invention are implemented in the form of a computer program product having a computer usable medium with computer readable program code, which can be read and used by a computer system in a conventional manner. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Those skilled in the art should more fully appreciate the advantages of the various embodiments of the present invention from the following "Detailed Description" discussed with reference to the drawings summarized below.

[0032] Figure 1A , 1B , 2A, 2B, 3A, 3B, 4A, 4B, 4C, 5, 6, and 7 schematically illustrate neuromodulation devices configured according to exemplary embodiments. It should be noted that the dimensions listed in these figures are illustrative and are not intended to limit the various embodiments.

[0033] Fig. 8A is an anatomical diagram illustrating various nerves and related anatomical structures in an exemplary embodiment.

[0034] Figure 8BThe innervation pattern of the target nerve according to an exemplary embodiment of the present invention is shown.

[0035] Fig. 9 is a neuromodulation process of an exemplary embodiment.

[0036] Figures 10A to 10B The process of converting the device from a closed configuration to an open configuration according to an exemplary embodiment is schematically illustrated.

[0037] Figures 10C to 10D The process of converting the device from a closed configuration to an open configuration according to an exemplary embodiment is schematically illustrated.

[0038] Fig.11 A close-up view of an arm of an exemplary embodiment of the invention is schematically shown.

[0039] Fig.12 Various orientations of the device body and channel / chamber directions of exemplary embodiments of the present invention are schematically shown.

[0040] Fig.13 A device with multiple electrodes and chambers is schematically shown according to an exemplary embodiment.

[0041] Fig.14 A detail of a protrusion on an arm of an exemplary embodiment is schematically shown.

[0042] Fig.15 , 16 17 schematically illustrate various electrodes of an exemplary embodiment.

[0043] Fig.18A , 18B , 18C, 18D, 18E, 18F, 18G, 18H, 19A, 19B, 19C, 20A, 20B and 20C schematically illustrate another embodiment of the neuromodulation device of the exemplary embodiment.

[0044] Fig.21 A neuromodulation device according to an exemplary embodiment is schematically shown.

[0045] Fig. 22 A neuromodulation device according to an exemplary embodiment is schematically shown.

[0046] Fig.23A , 23B and 23C schematically illustrate an exemplary embodiment of a neuromodulatory device.

[0047] Figures 24A to 24B A large diameter nerve located within a chamber is schematically shown in accordance with an exemplary embodiment.

[0048] It should be noted that the above drawings and the elements depicted therein are not necessarily drawn to consistent scale or any ratio. Unless the context otherwise requires, the same elements are represented by the same numbers. The drawings are mainly for illustrative purposes and are not intended to limit the scope of the inventive subject matter described herein. DETAILED DESCRIPTION

[0049] In an exemplary embodiment, a nerve is placed in a stimulation chamber of a neuromodulatory device. The device includes a movable arm that, when open, allows the nerve to enter the stimulation chamber. The arm, when closed, prevents or impedes the nerve from moving out of the stimulation chamber without excessively compressing the nerve. The movable arm is configured to hold nerves of various sizes within the chamber (e.g., the chamber accommodates nerves of 0.5 mm to 4 mm). In various embodiments, the arm is biased toward a closed or substantially closed position.

[0050] In addition, the device can be configured to hold nerves of different sizes in the chamber and in contact with the electrodes while applying a non-invasive holding force to the nerve. The channel is also configured to allow the nerve to pass in response to pressure from the nerve. The pressure required to open the channel is configured to be less than a pressure that can damage the nerve. Details of exemplary embodiments are discussed below.

[0051] Various embodiments further selectively stimulate peripheral nerves in areas of higher density of small nerves using a combination of lower power stimulation directed to specific neural targets without the need for destructive, time-consuming and / or traumatic surgery. Electrode arrays of the prior art disadvantageously fail to provide sufficiently specific stimulation to the target nerves and can result in unexpected side effects. Similarly, nerve cuffs are disadvantageously limited by predetermined dimensions and often do not achieve optimal results when coupled to inappropriately sized nerves. In addition, surgical implantation methods are time-consuming, invasive, and difficult to perform without damaging the nerves, particularly as the size of the target nerves decreases over time during the implantation process. Various embodiments disclosed herein advantageously deliver selective stimulation signals via electrodes that are in close contact with the target nerves in a simple implantation procedure.

[0052] In addition, various embodiments include a neuromodulatory device having a channel defined by a plurality of movable and / or deformable jaws or arms. The size of the channel is adjustable to allow nerves of various sizes to enter the chamber and to ensure that the nerve is secured therein, and the details of exemplary embodiments are discussed below.

[0053] Figures 1A to 4C A neuromodulation device 100 is schematically shown configured in accordance with an exemplary embodiment. To this end, the neuromodulation device 100 has a body 40 coupled to a movable arm 50 (also referred to as a movable jaw 50). The arm 50 may be hingedly coupled to the body 40 (e.g., such that the arm 50 pivots relative to the body 40).

[0054] In various embodiments, the body 40 can include a housing 48. The housing 48 can also enclose at least a portion of the movable arm 50. To this end, the housing 48 can be formed of an elastic or deformable material. The body 40 and the movable arm 50 (or the portion of the housing 48 surrounding the movable arm 50 and the body 40) can define a chamber 101, which is configured to receive the nerve 200 and a channel 102 leading to the chamber 101. In some embodiments, the chamber 101 can be defined by one or more arms 50. The chamber 101 contains at least one electrode 104 to stimulate the nerve 200.

[0055] The housing 48 encapsulates the package 46 of the main body 40. The housing 48 includes a buffer layer 49. As known to those skilled in the art, the package 46 encapsulates electronic devices and semiconductor materials. For example, the package 46 can contain different types of circuits, including stimulators, sensors, communications and / or power supply circuits. In various embodiments, the package 46 can be formed by a substantially rigid material, such as titanium, stainless steel, glass, ceramics, alumina, zirconium, plastics and / or other generally accepted airtight sealing packaging materials. In various embodiments, the electronic package and the nerve / connection electrode are integrated. In various embodiments, the feedthrough pin is not extended by the airtight sealing housing and welded to the electrode, but the electrode is formed by the feedthrough pin. In such an embodiment, the electrode is unwelded (i.e., there is no welding joint connecting it to the feedthrough pin). Instead, the feedthrough pin forms the electrode. When the feedthrough pin is embedded in a movable arm (e.g., silicone), it operates as a reinforcement of the deflection arm.

[0056] The package 46 forms an airtight seal around the internal electronic circuit. The electronic circuit is preferably enclosed in the airtight package 46 and sealed in an inert oxygen and low humidity (water-limited) environment. After the airtight seal is formed, two advantages are provided. First, the airtight seal ensures that the electronic package 46 will not enter the additional liquid, thereby causing electrical failure. Second, the airtight seal ensures that the non-biocompatible materials forming the internal electronic devices do not penetrate into the body.

[0057] Preferably, the package 46 is made of glass or ceramic materials, which have less interference with radio frequencies used for wireless power and wireless communications than other commonly used package 46 materials. The package 46 (also referred to as a hermetic seal 46) can be formed by glass wafers bonded directly to each other. Alternatively, the package 46 can be made of zirconia ceramic with brazed feedthroughs. In various embodiments, the package 46 can be sealed using a laser welded titanium surface brazed to the zirconia.

[0058] The cushioning layer 49 covers the encapsulation body 46, providing a second biocompatible layer and a suitable soft surface in the human body, as well as continuity with the portion contacting the nerve 200. As previously described, the arm 50 can include an overmolded housing 46 formed of a softer material (e.g., a Shore A durometer value of 30 to 50 durometer).

[0059] The buffer layer 49 can be formed of a material configured to conform to its resting position in the body. Although the arms 50 and the package body 46 can be encapsulated by the housing 48, the buffer layer 49 does not cover the electrodes 104. Therefore, the housing 48 can have openings for the electrodes 104 and / or the EMG 42. In addition, the through holes 45 can be formed through the housing. In various embodiments, the buffer layer 49 can encapsulate about 20% to about 99% of the device.

[0060] The vias 45 may extend through the package body 46 and / or the housing 48 (including the buffer layer 49). The electrodes 104 and other external electrical connections may be connected to the metallized vias 45. The metallized vias may be formed using platinum feedthroughs or the like. The package body 46 and the buffer layer 49 may be connected using RTV biocompatible silicone.

[0061] exist Figures 1A to 2B , the arm 50 is depicted in a closed position or a substantially closed position (collectively referred to as the closed position of the device), wherein the size of the channel 102 is small enough so that the nerve 200 cannot pass through the channel 102. The arm can be moved from the closed position to an open position, in which the size of the channel 102 is large enough so that the nerve 200 can pass through the channel 102. In some embodiments, the open position is large enough so that the nerve 200 can pass through the channel (e.g., by stretching and / or squeezing the nerve through the channel) with a diameter reduction of less than about 30% to about 50%. As described below, various embodiments can be configured to receive various nerve sizes. In various embodiments, the arm 50 can be biased toward the closed position (e.g., by using a biasing internal member 51). The medical staff can convert the arm 50 to the open position by applying a force to the arm 50 (e.g., by pulling the graspable extension 52) or by pressing the arm 50 with the nerve 200 itself. The nerve 200 can then enter or leave the chamber 101 through the channel 102.

[0062] like Figure 3A As shown in detail in FIG. 4 , various embodiments may include a protrusion 54 extending from the housing 48. In some embodiments, the protrusion 54 may be integrally formed with the housing 48 and / or the enclosure 46. The channel 102 may be at least partially formed between the protrusion 54 and the arm 50. The protrusion 54 may have a convex outer surface (e.g., a concave surface) configured to abut against the concave surface of the arm 50. Figure 3A). Protrusion 54 and arm 50 may have dimensions designed to prevent arm 50 from compressing nerve 200 in chamber 101 beyond a predetermined amount.

[0063] Although the discussion herein may refer to channels 102 formed between or defined by arms 50, it should be understood that this includes embodiments where arms 50 are enclosed by housing 48. Thus, the various embodiments are not limited to arms 50 that are uncovered.

[0064] Figure 3B Schematically, another embodiment is shown without a protrusion 54 extending from the body (eg, from the housing 48). Instead, the arm 50 may include the protrusion 54. Figure 3A Similarly, protrusion 54 and housing 48 can be configured to prevent arm 50 from squeezing nerve 200 in chamber 101 beyond a predetermined amount. In various embodiments, to enhance retention of nerve 200 within chamber 101, housing 48 can include a receiving portion 56 (e.g., a groove) configured to receive a portion of protrusion 54 (e.g., a tip).

[0065] like Figures 4A to 4B As shown, when nerve 200 is contained in chamber 101, nerve 200 is substantially prevented from moving in the X or Y direction (i.e., the force of arm 51 compressing nerve 200). Specifically, nerve 200 is sandwiched between nerve contact surface 58 (which may be concave) and electrode 104. As shown, nerve 200 may be slightly compressed. However, in some embodiments, chamber 101 may be sized such that nerve 200 is not compressed at all. In such embodiments, channel 102 is narrow enough in the closed position that nerve 200 cannot escape from or enter channel 102 under normal use. Figure 4A , movement of nerve 200 in the Z direction is not prevented (other than frictional forces that may be induced by moving nerve 200 through the compression region). Thus, in various embodiments, when arm 50 is in the closed configuration, movable arm 50 defines chamber 101 having a first open end and a second open end. Chamber 101 may also be fluidly coupled to channel 102, which is defined by movement of arm 50. Arm 50 may be moved such that the gap of channel 102 is less than the cross-sectional dimension of nerve 200 in the closed configuration (e.g., substantially zero). Arm 50 may also be moved such that the gap of channel 102 is greater than the cross-sectional dimension of nerve 200 in the open configuration.

[0066] It will be apparent to those skilled in the art that, unlike prior art nerve cuffs, in various embodiments, the electrode 104 only partially surrounds the nerve 200. In other words, the nerve 200 has a circumferential segment of the outer surface that is partially, but not completely, in contact with the electrode 104.

[0067] Figure 4C Another embodiment with an extended electrode 104A is schematically shown. In some embodiments, the extended electrode 104A can be the second electrode 104. The extended electrode 104A can stimulate the nerve 104 (if placed in the channel 102). In addition, the electrode 104A can be used to stimulate the nerve 200 and provide information to medical personnel (for example, the nerve 200 is not in the desired position within the chamber 101 that requires stimulation). In various embodiments, the electrode 104A can extend to the protrusion 54 and / or extend onto the protrusion 54. In some embodiments, the chamber 101 can have the function of a recording chamber 101 and / or a stimulation chamber 101. For example, the recording chamber 101 can record electrical activity within the chamber 101, and the stimulation chamber 101 can induce electrical stimulation within the chamber 101. To this end, the electrode 104 (and / or the electrode 104A) can be used to record signals from the nerve 200 and / or stimulate the nerve 200.

[0068] The device 100 can be made at least in part from a polymer and a selected metal. For example, in some embodiments, the neuromodulation device 100 is fabricated using a flexible polyimide / SiC substrate that is gold metallized at an ultra-microscale using established thin film and photolithography methods. In another example, the device 100 can be made from SU-8 or other such polymers using commonly used micromachining and photoresist techniques.

[0069] As described above, the device 100 has conductive components. For example, the device 100 can be connected to an electrical pulse generator and / or an electrical stimulator (sometimes collectively referred to as a "signal generator"). In some cases, the device 100 can include circuitry for communicating with the signal generator. For example, the communication circuitry can facilitate magnetic inductive coupling or direct conductive coupling (e.g., via wires or other hard-wired electrical interfaces).

[0070] Chamber 101 is configured to receive nerve 200 (e.g., a human somatic motor nerve). Nerve 200 may include a plurality of nerve axons, nerve fibers, nerve bundles, nerve fascicles, or other similar neuroanatomical structures. However, it should be understood that nerve 200 is preferably a fully functional nerve or a partially functional nerve. For example, a fully functional nerve should have functional presynaptic and postsynaptic terminals and should be functionally capable of propagating action potentials. For example, in some embodiments, the average diameter of nerve 200 may be at least 100 μm, at least 200 μm, at least 300 μm, at least 400 μm, at least 500 μm, at least 600 μm, at least 700 μm, at least 800 μm, or at least 900 μm. In some embodiments, the average diameter of nerve 200 may be about 50 μm to 4 mm, about 50 μm to 3.5 mm, or other ranges between the above exemplary sizes.

[0071] In some embodiments, chamber 101 can be generally cylindrical in shape, wherein the ends of cylindrical chamber 101 are open to allow nerve 200 to exit longitudinally from chamber 101 toward the presynaptic and postsynaptic terminals of nerve 200. Although a cylinder comprises a circular cross-sectional shape, it should be understood that chamber 101 can also comprise a triangular, quadrilateral, pentagonal, hexagonal, or polygonal cross-sectional shape having n sides while maintaining a general three-dimensional structure similar to a cylinder or a tube having an opening and being operable to receive nerve 200. Some embodiments of chamber 101 do not have a specific cross-sectional shape, but can be an irregular cross-sectional shape.

[0072] In some embodiments, chamber 101 can be in fluid communication with an outer surface 103 and a second (opposite) outer surface 103 of device 100. Specifically, the first outer surface and the second outer surface 103 in this example are located on opposite sides of device 100 and chamber 101, and device 100 and chamber 101 are located between the first outer surface and the second outer surface, and are in fluid communication with each of the opposite first and second outer surfaces 103 of device 100.

[0073] As a three-dimensional area, chamber 101 has a length, a depth, and a height. The length of chamber 101 corresponds to the z-axis that moves longitudinally along the nerve 200 passing through device 100. The depth of chamber 101 corresponds to the x-axis, and the height corresponds to the y-axis. In some embodiments, the average length of chamber 101 can be at least 50 μm, at least 100 μm, at least 500 μm, or at least 1000 μm. In some embodiments, the average length of chamber 101 can be about 50 μm to 11 mm (e.g., about 2 mm). In some embodiments, the average length of chamber 101 can be about 10 μm to 5 mm, about 10 μm to 3 mm, about 10 μm to 1 mm, about 50 μm to 2 mm, about 50 μm to 11 mm, or about 10 μm to 11 mm.

[0074] The various dimensions of chamber 101 are described below. It should be assumed that the dimensions of chamber 101 are the dimensions of the chamber when it is in the closed position. As previously described, chamber 101 is defined in part by movable arm 50. Therefore, chamber 101 has a closed configuration (also referred to as the closed position) and an open configuration (also referred to as the open position). The chamber also has intermediate configurations between the open configuration and the closed configuration, but the final configuration is described herein. Unless the context requires otherwise, it should be assumed that the dimensions of chamber 101 described herein refer to the closed configuration.

[0075] As described above, the depth and height of the chamber 101 can be considered to correspond to the cross-sectional dimensions of the xy plane orthogonal to the z-axis of the chamber 101. For example, a cylindrical chamber 101 can have a depth and height corresponding to the diameter of the chamber 101. The diameter of the non-cylindrical chamber 101 can be measured by measuring the average of the distances intersected by the center point of the cross section of the chamber 101, wherein the center point is located on the z-axis extending through the middle of the chamber 101. In some embodiments, the average diameter of the chamber 101 can be less than 10 mm. In some embodiments, the average diameter of the chamber 101 is about 10 μm (micrometer) to about 2000 μm, about 10 μm to about 4000 μm, 10 μm to about 3000 μm, about 1 μm to 2000 μm, about 10 μm to 1000 μm, about 10 μm to 900 μm, or about 10 to 800 μm, or about 10 μm to 500 μm.

[0076] In some embodiments, the average diameter of the chamber 101 is substantially the same as the average diameter of the target nerve 200 or is 10% smaller than the average diameter of the target nerve 200. In some embodiments, the average diameter of the chamber 101 is no more than 5% larger or no more than 5% smaller than the average diameter of the target nerve 200. In some embodiments, the average diameter of the chamber 101 is no more than 15% larger or no more than 15% smaller than the average diameter of the target nerve 200. For example, for a target nerve 200 having an average diameter of about 80 μm, the average diameter of the device 100 may be no less than about 56 μm and no more than 104 μm. In some embodiments, the average diameter of the chamber 101 is about 80% to 120% of the target nerve 200, about 85% to 115% of the target nerve 200, about 90% to 110% of the target nerve 200, about 95% to 105% of the target nerve 200, or about 100% of the target nerve 200 or the same size.

[0077] In some embodiments, channel 102 is defined by two walls that can provide an upper boundary and a lower channel boundary. In some cases, the distal end of channel 102 can be in fluid communication with the interior of chamber 101, and the proximal end of channel 102 can be in fluid communication with the outer surface 103 of device 100. Therefore, the distal end of channel 102 leads to chamber 101. In some embodiments, chamber 101 leads to channel 102 indefinitely or continuously, so that the distal opening of channel 102 to chamber 101 is not closed. In addition, channel 102 can connect the interior of chamber 101 with the outer surface 103 of device 100. Therefore, in this embodiment, chamber 101 substantially maintains constant communication with the outer surface 103 of device through channel 102. For example, chamber 101 always remains open to channel, and channel 102 always remains open to the outer surface.

[0078] Various dimensions of the channel 102 are described below. It should be assumed that the dimensions of the channel 102 refer to the dimensions when the channel 102 is in the closed position. As previously described, the channel 102 is partially defined by the movable arm 50. Therefore, the channel 102 has a closed configuration (also referred to as the closed position) and an open configuration (also referred to as the open position). The channel 102 also has intermediate configurations between the open configuration and the closed configuration, but the terminal configuration is described herein. Unless the context indicates otherwise, it should be assumed that the dimensions of the channel 102 described herein refer to the open configuration. This is in contrast to the discussion of the chamber 101, which generally refers to the dimensions of the chamber in the closed configuration.

[0079] As a three-dimensional area, channel 102 has a length, a height, and a width (also referred to as a gap or opening). Similar to the length of chamber 101 described above, the length of channel 102 corresponds to a measurement along the z-axis, which extends longitudinally along nerve 200. It can be measured at any point between the distal end of the channel opening of channel 102 leading to chamber 101 and the proximal end of the channel opening leading to the outer surface 103 of the device. In some embodiments, the distal end of channel 102 can be in fluid communication with chamber 101 over the entire length of chamber 101. In some cases, the average length of channel 102 is substantially the same as the average length of chamber 101 of device 100 described herein. In various embodiments, the length of channel 102 and / or chamber 101 does not change from an open position to a closed position.

[0080] In some embodiments, the average length of the channel 102 can be at least 100 μm. In some embodiments, the average length of the channel 102 can be at least 1000 μm, at least 2000 μm, or at least 4000 μm, or at least 6000 μm. In some embodiments, the average length of the channel 102 can be about 100 μm to about 10 mm. In some embodiments, the average length of the channel 102 can be about 100 μm to 6 mm, about 100 μm to 3 mm, about 100 μm to 8 mm, or about 10 μm to 9 mm (e.g., embodiments of devices having batteries).

[0081] The height of the channel 102 corresponds to the measured distance between the distal opening and the proximal opening of the channel 102, wherein the distance is measured along an imaginary centerline placed equidistant between each channel wall. In some cases, the height can be a linear measurement. For example, in some cases, the channel 102 is a linear channel 102. In other cases, the channel 102 can be non-linear, wherein the non-linear channel includes one or more turns, curved segments, or angles in the channel wall (e.g., from the protrusion 54). Therefore, in some cases, the height of the non-linear channel 102 can be measured by measuring the distance between the distal opening and the proximal opening of the channel 102 and along each bend in the non-linear channel 102 along the virtual centerline of the channel 102. For example, in some embodiments, the channel 102 can include an "L" shape, so that the channel 102 height measurement includes a 90-degree turn, and each end of the "L" corresponds to the distal opening and the proximal opening of the channel. In an exemplary channel having a 90 degree turn, the height can be measured by adding the distances extending from the imaginary centerline of the channel of each arm of the "L" shaped arm of the channel 102 between the proximal and distal openings of the channel 102 to the intersection of the imaginary lines of each arm. The shape of the channel can also include other configurations, such as T, Z, S, etc.

[0082] In some embodiments, the average height of the channel 102 can be about 100 μm to 5 mm (e.g., 4.5 mm). In some embodiments, the average height of the channel 102 can be about 100 μm to 5 mm, about 100 μm to 1 mm, about 100 μm to 2 mm, about 100 μm to 3 mm, about 100 μm to 4 mm, or about 100 μm to 5 mm.

[0083] As described above, the width of the channel 102 corresponds to the measurement of the channel 102 in the xy plane orthogonal to the z-axis. The width of the channel 102 can be constant so that the width of the channel 102 does not change between the proximal opening and the distal opening of the channel 102. That is, in some embodiments, the width of the channel 102 includes an average width variation of less than 10% over the entire height of the channel 102. In some cases, the channel 102 includes an average width variation of less than 5%, less than 3%, or less than 2% over the entire height measurement of the channel 102. In some cases, the width can be determined by measuring the shortest distance between the body 40 (e.g., the housing 48) and the arm 50.

[0084] In some embodiments, the width of the channel 102 is less than the diameter of the target nerve 200. For example, in some embodiments, the width of the channel 102 can be at least 5% less than the diameter of the target nerve 200. In some embodiments, the width of the channel 102 can be at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, or at least 50% less than the diameter of the nerve 200. In some embodiments, the width of the channel 102 can be no less than 60% less than the diameter of the target nerve 200. In other embodiments, the width of the channel 102 can be no less than 50% less than the diameter of the target nerve 200. In some embodiments, the width of the channel 102 can be approximately 5% to 60% less than the diameter of the target nerve 200. In some cases, the width of channel 102 can be approximately 10% to 50%, approximately 10% to 40%, approximately 15% to 40%, approximately 20% to 35%, or approximately 20% to 40% smaller than the diameter of target nerve 200 .

[0085] In addition, similar to the chamber 101 described above, the channel 102 can have an open end in fluid communication with the open end of the chamber 101, so that when the channel 102 is in an open position, the nerve 200 can be inserted into the chamber 101 by sliding, moving or inserting the longitudinal portion of the nerve 200 into the chamber 101 through the channel 102. Therefore, the channel 102 is configured to receive the target nerve 200. In addition, in some embodiments, the channel 102 can be in fluid communication with one, two, or all three outer surfaces 103 of the device 100. For example, the channel 102 can be open to the interior of the chamber 101 at the distal end of the channel, the channel can extend along the height of the channel to the third outer surface 103 at the proximal end of the channel, and at the same time be in fluid communication with the first outer surface 103 and the second outer surface 103 on opposite sides of the device 100 corresponding to opposite ends of the z-axis.

[0086] As described above, the device 100 has at least one electrode 104 in the chamber 101. The electrode 104 can include various types of electrodes, including fiber or flat electrodes, thin film electrodes, or needle electrodes. For example, the electrode 104, when coupled to the chamber 101, can act as a thin film electrode that records or stimulates a surface within 100-2000 μm2, or within 50 μm of the outer surface of the nerve 200. The needle electrode in the chamber can have a needle-shaped recording and / or stimulation surface that can penetrate the surface of the nerve 200 when in the chamber 101. The electrode that penetrates the nerve in the chamber 101 stimulates and / or records intraneurally, thereby providing greater selectivity and / or resolution when recording and / or stimulating. In addition, the electrode 104 can be placed on any other surface in the chamber 101, including the top, bottom, and / or side chamber surfaces.

[0087] When chamber 101 has multiple electrodes 104, a combination of multiple electrode types can be used. For example, flat electrodes and / or needle electrodes can be used in recording and / or stimulation chamber 101. Among them, electrode 104 can be a monopolar, bipolar, tripolar or multi-electrode array electrode, etc. In some cases, multiple electrodes 104 can be configured in a tripolar configuration, which should provide improved neural specificity and / or selectivity while reducing external biological noise.

[0088] As described above, electrode 104 may be formed at least in part by one or more conductive metals. For example, the electrode may be formed at least in part by gold, titanium nitride (TiN), iridium oxide (IrO), iridium, carbon nanotubes, graphene, graphene oxide and / or platinum (Pt). In some cases, electrode 104 may have a charge injection capacity of about 0.1 mC / cm2 or more. In addition, in some embodiments, electrode 104 may be a wired electrode or a wireless electrode. Wireless electrode 104 may have a wireless integrated circuit capable of communicating with an external device.

[0089] In some embodiments, the electrode 104 may have a thickness of about 25 μm. 2 Up to 25mm 2 In some cases, the electrodes comprise approximately 100 μm 2 Up to 1mm 2 or about 100 μm 2 Up to 0.5mm 2 of stimulation and / or recording surface area.

[0090] Exemplary embodiments use specified neuromodulation techniques to selectively activate one or more pelvic floor muscles. Wherein, these pelvic floor muscles may include cremaster muscle, bulbar muscle (Bgm), sciatic cavernous muscle (Ism), bulbospongiosus muscle (Bsm), pubococcygeus muscle (Pcm), iliococcygeus muscle (Icm), coccygeus muscle (Cgm) or puborectalis muscle (Prm) etc. However, it is preferred to use the perineal nerve to drive the pubococcygeus muscle. Alternatively, the pubococcygeus branch may also be used for driving. In some embodiments, the pelvic floor muscles may be neuromodulated or stimulated simultaneously with or independently of one or more other pelvic floor muscles. In some cases, the pelvic nerve may include any nerve, nerve bundle, nerve fascicle or nerve fiber bundle (nerve tract), which innervates the pelvic floor muscles or pelvic organs, including the pudendal nerve, clitoral nerve or dorsal nerve of the penis, or any branch of these nerves or other nerves in the pelvis. In various embodiments, some embodiments can be used to help treat pelvic organ prolapse by stimulating the distal terminal branches of the pudendal nerve (e.g., perineal nerve, inferior rectal nerve) and / or the terminal branches of the levator ani nerve. In addition, some embodiments can also be used in veterinary applications to stimulate animal nerves.

[0091] It should be understood that the above-described device 100 is only one example of a neuromodulation device that can be used to stimulate appropriate somatic nerves. For example, two or more devices 100 can be used to stimulate two or more pelvic floor muscles or organs. In addition, because the device 100 can record and / or stimulate, two or more devices can be used on the same pelvic floor muscle to record and stimulate independently, or one device can be used to record and stimulate a pelvic floor muscle or organ.

[0092] Figure 5 Another embodiment of the device 100 of the exemplary embodiment is schematically shown. Note that this figure has different reference numbers for the same components as described above, but similar components have the same or similar functions. As shown, the device includes a battery or other powered pulse generator and electronic controller 1901, which is connected to an electrode 1905 via a wire 1903. As shown, the electrode is part of a chamber 1907 of a neuromodulation device 1911. As shown, the neuromodulation device 1911 can include a curved channel 1909 that can be configured to receive a nerve. In some embodiments, at least a portion of the width of the channel 1901 can be smaller than the diameter of the target nerve in the closed configuration and / or the open configuration. Therefore, the target nerve can be temporarily reversibly compressed or stretched and slide through the channel until the target nerve is fixed within the chamber 1907. In some embodiments, the diameter of the chamber 1907 can be larger than the nerve so that the nerve is not compressed or stretched within the chamber 1907. Alternatively, the diameter of the chamber 1907 can be smaller than the nerve. Thus, in such an embodiment, at least a portion of the nerve can extend into channel 1909, while the majority of the nerve is contained within chamber 1907. In addition, chamber 1907 can provide an isolated fluid environment that allows for targeted, specific stimulation of the portion of the nerve held within chamber 1907.

[0093] Figure 6 Schematically illustrates an exemplary embodiment of a wireless neuromodulation device and an external system. Figure 5Similarly, this figure has different reference numerals for the same components as described above, but similar components have the same or similar functions. The device has an external battery or other power supply pulse generator and electronic controller 2001, which includes a coil for transmitting power, data and / or control signals to the wireless neuromodulation device 2013. In particular, the electromagnetic field 2003 can couple the pulse generator and electronic controller 2001 to the wireless neuromodulation device 2013. The corresponding electronic devices and magnetic induction coil 2005 in the neuromodulation device 2013 can be connected to a conductive material used as an electrode 2007. The electrode 2007 can form a part of the chamber 2009. As described in other embodiments, the neuromodulation device of this figure can include a chamber 2009 configured to receive a nerve, and a channel 2011 (e.g., an expandable gap) through which the nerve can pass when placed in the chamber 2009.

[0094] Figure 7 Another wireless implementation of the system is schematically shown. Figures 5 to 7 Similarly, components identical to those described above are labeled with different reference numerals, but similar components have the same or similar functions. To this end, an external battery powered pulse generator and electronic controller 2101 with a coil is configured to transmit power, data, and / or control signals to a neuromodulation device 2115. An electromagnetic field 2103 couples with the coil 2105 of the neuromodulation device 2115. In some embodiments, the electronics and coil 2105 can be isolated and implanted separately from the stimulation element of the neuromodulation device 2115. The location of the electronics and coil 2105 can be selected to optimize the signal strength and transmission quality between the external pulse generator and electronic controller 2101 and the neuromodulation device 2115.

[0095] Additionally, the configuration of the separate electronics and coil 2105 can reduce battery requirements and the voltage and / or amplitude applied. Wires 2107 can couple the electronics and coil 2105 to the neuromodulation device 2115, and more specifically, to electrodes 2109 located within the chamber 2111. As with some other embodiments, the neuromodulation device 2115 can include a chamber 2111 configured to receive a nerve, and a channel 2113 (or expandable gap) through which the nerve can pass when placed in the chamber 2111.

[0096] Among other advantages, connecting the implantable electronics with the receive coil to the neuromodulation device effectively decouples the receive coil. This allows medical personnel to implant the receive coil in the same location and orientation relative to the body's hard tissue structures, regardless of where the electrodes and neuromodulation device are located. The consistency of the receive coil location and orientation is expected to provide more consistent, efficient, and reliable coupling and induction in the implanted coil and electronics. This can help avoid changes in stimulation or changes in the need for external coil location or orientation.

[0097] Based on the inventors' experiments, they have found that stimulation of the pelvic floor muscles can activate sensory fibers that have not been previously associated with urinary incontinence. Specifically, this includes proprioceptive type Ia and type Ib large myelinated sensory afferents. Using appropriate parameters / specifications, these sensory afferents can be targeted for selective neuromodulation to activate previously unknown central nervous system sensory pathways, including those in the spinal cord and brainstem involved in storage / voiding control.

[0098] To this end, the inventors surprisingly found that acute wireless stimulation of the bulbocavernosus nerve in certain animals significantly increased maximum urethral pressure and urination efficiency, proportional to the frequency of stimulation. Acute stimulation was sufficient to increase urethral pressure and urination volume by 3-fold, suggesting that activation of this perineal nerve strengthens the urethral sphincter that supports continence and urination efficiency. This result confirms that a miniature wireless stimulator can effectively contract the pelvic floor muscles and serve as a strategy to reverse SUI-like features in elderly and multiparous rabbits.

[0099] The coccygeal plexus is anatomically and functionally distinct from the pelvic plexus, which contains the pudendal nerve. Thus, sacral neuromodulation (SNM), percutaneous tibial nerve stimulation (PTNS), and pudendal nerve stimulation (PNS) are all part of the pelvic plexus, primarily targeting the same sacral (S2-3) level in the spinal cord, where axons in the sacral or peripheral nerves are anatomically and functionally intermingled with pain, mechanoreceptive motor, proprioceptive, and autonomic neurons. The inventors believe (but have not yet confirmed) that the mechanism of action of SNM, PTNS, and PNS for the treatment or urge urinary incontinence involves the modulation of mechanosensory afferent fibers.

[0100] In contrast, the inventors have found that the axons innervating the pelvic floor muscles are innervated by either the pelvic plexus or the coccygeal plexus, which are more anatomically and functionally consistent, consisting primarily of motor somatic efferents and proprioceptive (Ia / Ib) sensory afferents, which enter the spinal cord via the perineal nerve and / or the levator ani nerve via anterior (S2-3) and / or more posterior (S4-5) spinal cord levels, respectively. However, proprioceptive axons ascend all the way to lumbar vertebra (L) 7, linking the function of the PFM to that of the bladder and other pelvic organs. Therefore, the inventors have found that stimulating proprioceptive sensory afferents also inhibits bladder activity, and have therefore found that such stimulation may be an effective method for treating overactive bladder. An exemplary embodiment selects the motor branch of the perineal nerve that controls the pubococcygeus muscle. For details, see Fig. 8A .

[0101] Figure 8B The innervation pattern of the target nerve of an exemplary embodiment of the present invention is shown. As shown, the pubococcygeus muscle is innervated by the perineal plexus and the coccygeal nerve from branches at different ends. Although the pelvic nerve is a branch of the perineal plexus that innervates the anterior Pcm, it also receives innervation from the pubococcygeus nerve that branches from the levator ani muscle. The percentage of innervation is derived based on the two reference numbers listed in the slide.

[0102] Various embodiments can combine and stimulate nerves to treat, inter alia, female sexual dysfunction, male erectile dysfunction, fecal incontinence (which can include, but is not limited to, sacral nerve stimulation), overactive bladder / urge incontinence (including, but not limited to, sacral nerve stimulation or tibial nerve stimulation), pain management (including chronic pelvic pain), headaches, somatic (i.e., muscles, extremities) and visceral (by activating mechanoreceptive or proprioceptive fibers that compete with nociceptive signals or directly blocking signals from pain fibers), blood pressure management, sleep apnea, nausea stimulation, tremor stimulation, and / or stimulation of the vagus nerve, sacral nerve roots, and abdominal nerve roots, stimulation for various applications, etc. Various embodiments can stimulate various nerves according to the stimulation parameters provided herein (e.g., for OAB and SUI), and stimulate other treatments according to the same or different parameters (e.g., for OAB and / or SUI).

[0103] Fig. 9 A neuromodulation process of an exemplary embodiment is shown. It should be noted that the process is simplified from a longer process that is commonly used. Therefore, the process has many steps used by those skilled in the art. In addition, some steps can be performed in an order that may be different from the order shown. In addition, or alternatively, some steps can be performed simultaneously. Therefore, those skilled in the art can modify the process as needed.

[0104] The process uses at least one "control signal" to neuromodulate the appropriate motor and proprioceptive nerve branches from the coccygeal plexus and / or the perineal plexus (in this case, the perineal nerve). These control signals are called:

[0105] 1) "OAB control signals" for controlling overactive bladder, and

[0106] 2) "SUI control signal" for controlling stress urinary incontinence.

[0107] therefore, Fig. 9 The process begins at step 1000, which sets the specifications of the control signals. In various embodiments, the control signals may be OAB and / or SI control signals. These specifications may be stored in a database, memory, or other storage medium for use in subsequent steps. Such a location may be, among other locations, a part of the device 100 itself, a part of a signal generator, somewhere on a local area network (e.g., an enterprise network), or somewhere on a larger wide area network (e.g., the Internet). The inventors have determined using calculations and experiments that the subsequent specifications should produce satisfactory results.

[0108] The process uses at least one "control signal" to neuromodulate the appropriate nerve, such as the coccygeal plexus somatic nerve, which in this case would be the perineal nerve. These control signals are called:

[0109] 1) “OAB control signals” – stimulation parameters used to manage overactive bladder, and

[0110] 2) “SUI control signals” – stimulation parameters used to manage stress urinary incontinence.

[0111] Specifically, the OAB control signal may have one or more of the following sets of specifications for humans:

[0112] The amplitude is about 0.4 mA to 1 mA,

[0113] The pulse duration of each pulse is about 200 microseconds to 400 microseconds (when the OAB control signal is a periodic signal),

[0114] A frequency of about 5 Hz to 20 Hz (when the OAB control signal is a periodic signal), and

[0115] The duty cycle is about 5% to 100% (eg, more specifically about 8% to 12%).

[0116] The stimulation pulse lasts for about 10 to 20 seconds, followed by a 2.5 minute OFF period, repeated at least 3 to 4 times in a single session

[0117] The duration of transmitting OAB control signals during a single connection shall not be less than 10 minutes and not more than 30 minutes.

[0118] These values ​​can be adjusted appropriately for different mammals. In addition, these values ​​can be adjusted according to the number of treatments per day or week, the individual and / or the severity of the disease.

[0119] The SUI control signal may have one or more of the following specifications for humans:

[0120] The amplitude is about 0.5 mA to 2 mA,

[0121] The pulse duration of each pulse is about 200 microseconds to 400 microseconds (for example, when the OAB control signal is a periodic signal),

[0122] A frequency of about 60 Hz to 100 Hz (when the OAB control signal is a periodic signal), and

[0123] The duty cycle is about 5% to 100% (eg, more specifically about 8% to 12%).

[0124] The stimulation pulse lasts for about 10 to 20 seconds, followed by a 2.5 minute OFF period, repeated at least 3 to 4 times in a single session

[0125] The duration of transmitting the SUI control signal during a single connection shall not be less than 30 seconds and not more than 120 seconds.

[0126] As another example, the OAB control signal may have the following set of one or more rules for humans:

[0127] grid:

[0128] The amplitude is about 0.4 mA to 1 mA,

[0129] The pulse duration of each pulse is about 200 microseconds to 400 microseconds (when the OAB control signal is a periodic signal),

[0130] A frequency of about 5 Hz to 20 Hz (when the OAB control signal is a periodic signal), and

[0131] The duration of OAB control signal transmission during a single connection shall not be less than 10 minutes and not more than 30 minutes.

[0132] These values ​​can be adjusted appropriately for different mammals. In addition, these values ​​can be adjusted according to the number of treatments per day or week, the individual and / or the severity of the disease.

[0133] The SUI control signal may have one or more of the following specifications for humans:

[0134] The amplitude is about 0.4 mA to 4 mA,

[0135] The pulse duration of each pulse is about 200 microseconds to 400 microseconds (for example, when the OAB control signal is a periodic signal),

[0136] A frequency of about 60 Hz to 100 Hz (for example, when the OAB control signal is a periodic signal), and

[0137] The duration of the SUI control signal during a single connection is not less than 30 seconds and not more than 120 seconds.

[0138] As with the specifications for the OAB control signal, these values ​​can be adjusted appropriately for different mammals. In addition, these values ​​can be adjusted based on the number of treatments per day or week, the individual, and / or the severity of the disease.

[0139] Typically, the frequency of symptom control signals for pelvic floor neuromodulation can be about 2 Hz to about 100 Hz. Nerve blocking signals can use higher frequencies, such as about 1 kHz to about 40 kHz. However, some embodiments can use lower frequencies (e.g., <10 Hz for nerve blocking).

[0140] Advantageously, the same neuromodulation device 100 may be used to deliver both afferent and efferent control signals over the same nerve.

[0141]

[0142] The inventors' experiments have shown that the use of the above-mentioned stimulation parameters to stimulate the efferent nerve can close the external rectal sphincter and the secondary rectal sphincter.

[0143] Details of various control signals that may be used are described in co-pending US Patent Application No. 17 / 985,843, which is incorporated herein by reference in its entirety.

[0144] The process continues to step 1001, which converts the device 100 to an open configuration. As previously described, the device 100 has an open configuration and a closed configuration. Fig. 10A and 10C Various embodiments of the device 100 are schematically shown in a closed configuration. In the closed configuration, the depth of the channel 102 (also referred to as the gap) between the movable arm 50 and the housing 48 (or the protrusion 54) is small enough that the target nerve cannot enter the chamber 101 through the channel 102 without being damaged. Therefore, conversion to the open configuration allows the nerve to enter the chamber.

[0145] Fig. 10B and 10DVarious embodiments of the device 100 in an open configuration are schematically shown. In various embodiments, the opening of the channel can be tapered or "V" shaped to help guide the nerve into the chamber. In the open configuration, the depth of the channel 102 is large enough so that the nerve can enter the chamber 101 through the channel 102. It should be understood that the open configuration can be but does not necessarily have to be the maximum open position. This means that the device can be in an open configuration even if the arm 50 can be moved additionally to make the gap larger. In various embodiments, the size of the gap can be determined by measuring the shortest distance between the housing 48 and the arm 50.

[0146] In various embodiments, the size of the gap in the closed configuration is equal to or less than the diameter of the target nerve 200. For example, the size of the closed gap can be configured to be 30 to 50% smaller than the target nerve 200. In various embodiments, the gap in the closed configuration can be about 0 mm to about 0.7 mm, for example, 0.5 mm. In various embodiments, the gap in the open configuration can be about 0.75 mm, 1.75 mm, or 2.75 mm.

[0147] The transition to the open configuration can be accomplished by the medical professional pulling on the movable arm 50 to create a gap and / or increase the size of the gap to allow the passage of a nerve (or a stretched nerve), pressing a button, or using the nerve itself to open the passage. In other embodiments, the arm 50 can be electrically operated (e.g., by pressing a button). In other embodiments, the biased arm 50 (e.g., a polymer "loaded spring" within an elastic range, the elastic properties of the material itself, the addition of a spring, etc.) can be pre-opened, or can be opened using a delivery system or tool.

[0148] In some other embodiments, the force of the nerve pressing on the biasing arm 50 is sufficient to move the biasing arm 50 and allow the nerve to pass. In various embodiments, the medical practitioner can stretch the nerve to reduce the diameter of the nerve, and the nerve can fit into the opening of the channel 102. The reduced diameter of the nerve allows the medical practitioner to slide the nerve into the slightly open (i.e., open configuration) channel 102 to allow the nerve to pass. After the nerve passes through the channel 102, the medical practitioner closes the channel back to its closed configuration and retains the unstretched nerve in the chamber 101. In the chamber 101, the medical practitioner stops stretching the nerve, so the nerve remains in the chamber.

[0149] As described above, the process continues to step 1002, which couples the electrode to a somatic nerve (e.g., the perineal nerve). Thus, medical personnel can align the nerve with the channel 102 and place the perineal nerve through the channel 102. The nerve 200 can then be secured in the chamber 101.

[0150] In some embodiments, the nerve 200 can be stretched to a thinner cross-sectional dimension to allow it to pass through the channel 102. If the nerve 200 is stretched briefly, it is released in the "free" region at the bottom of the chamber where the nerve recovers and returns to approximately its original shape and size. However, in some embodiments, the gap of the channel 102 is large enough to allow the unstretched nerve 200 to pass through. When coupled in the chamber 101, depending on the size of the nerve, the nerve can relax or return to its normal state.

[0151] The process then proceeds to step 1003, which converts the device to a closed configuration. As previously described, the arms 50 can be biased closed. Thus, the medical professional only needs to remove the force used to open the arms 50, and the biasing force closes the channel 102 and moves to the closed configuration. As previously described, the closed configuration does not necessarily need to have zero gap. In some embodiments, the gap is small enough to prevent the nerve from moving out of the chamber 101.

[0152] In various embodiments, the movable arm 50 can be spring loaded. Thus, the movable arm feature can also be referred to as a "clip" that allows the nerve to be in the chamber in an uncompressed state, but with a gentle holding force to press the nerve toward the electrode. As the nerve moves down the channel, the spring force of the fixed arm 50 returns to the resting position and gently holds the nerve 200 in place. (Alternatively, the spring loaded fixed arm 50 can remain open until the nerve is fully in the chamber and then return to the resting position.)

[0153] The channel can accommodate nerves 200 of various sizes. The inventors have determined that the movable arms of various embodiments can effectively accommodate nerves 200 with cross-sectional dimensions varying by up to 400% or more (e.g., 1 mm nerve to 4 mm nerve). Various embodiments utilize a channel-chamber orientation, where the channel defined by the spring-loaded arms accommodates the stretched nerve 200, rather than being "fixed" in place by a clamp, so that the spring loading does not apply undue pressure to the nerve. The nerve 200 moves down the channel (e.g., a variable width channel) based on the position of the spring-loaded arms and resides in a chamber area, the size of which also varies with the size of the nerve due to the same spring arms. As the channel slowly closes under the action of the spring force, the directional characteristics of the chamber wall help maximize contact with the electrode.

[0154] Thus, it should be appreciated that in the closed configuration, nerve 200 may be slightly compressed by arms 50 (eg, nerve contact surface 58). However, in other embodiments, nerve 200 may not be compressed by arms 50, but may simply be trapped within chamber 101.

[0155] As described above, the nerve is preferably directly conductively coupled to the electrode 104. Therefore, preferably, there are no other non-negligible organic components of the patient between the nerve and the device 100 (e.g., the electrode 104 and the nerve). Some embodiments may have a coating or other structure on the electrode 104, but can still be directly connected or coupled to the nerve.

[0156] The process then proceeds to step 1004. With the nerve secured in chamber 101, the signal generator can begin transmitting an OAB control signal to device 100 through electrode 104 and to the perineal nerve (step 1004). Over time, the signal reverses and returns the OAB symptoms to normal. The stimulation activates the pelvic floor in a specified manner. However, during the experiment, the inventors were surprised to find that the signal appeared to mitigate the effects of the natural OAB signal on the pelvic floor. Specifically, the patient's body naturally sends OAB signals (referred to as "natural OAB signals"), which are part of the patient's mechanism for triggering OAB symptoms. However, this activation on the perineal nerve appears to block or otherwise interfere with the body's response to the natural OAB signal, thereby weakening or otherwise mitigating the effects of the natural OAB signal.

[0157] As described above, for a single connection, the method can transmit the OAB control signal to the perineal nerve for approximately 10 to 30 minutes. As described above, the timing can be fine-tuned based on the patient's condition, the severity of the disease, etc. After the OAB signal treatment is completed, the process can continue to optional step 1006 to also treat SUI. In addition, or alternatively, the process can send a FI signal to treat FI. Specifically, if the patient also suffers from SUI, the method can transmit the SUI control signal to the perineal nerve in this connection for 30 to 120 seconds. In addition, or alternatively, the process can send a FI signal to treat FI. Other embodiments can exchange the order of steps 1004 and 1006.

[0158] The process then proceeds to step 1007 where the nerve is removed from chamber 102. Some embodiments may be permanently implanted and thus this step may be skipped. However, advantageously, various embodiments may be easily removable. As previously described, the device is converted to an open configuration. In some embodiments, medical personnel may use a tool to do this. In other embodiments, medical personnel may stretch the nerve and may pass it through channel 102. The force of the nerve may slightly open channel 102 to the open configuration. After the nerve is removed from chamber 101, channel 102 may return to its biased closed configuration.

[0159] Although various embodiments relate to movable arms that transition between an open configuration and a closed configuration, some embodiments may have immovable arms or fixed arms. In such embodiments, channel 102 may be configured so that a nerve can pass through atraumatically when stretched. To this end, the material of arm 50 (e.g., a cushioning layer) may be sufficiently soft so that it deforms to allow nerve 200 to pass through.

[0160] Part or all of the process can be implemented by hardware, software, or both. For example, part or all of the process can be implemented using a custom ASIC, FPGA, microcontroller, or other logic and software (e.g., firmware) and integrated with the rest of the system.

[0161] Thus, the inventors discovered that they could treat OAB and SUI through relatively easily accessible somatic nerves, such as the perineal nerve. Advantageously, such nerves are very small, and therefore require much less power than many other conventional nerve stimulation systems.

[0162] Fig.11 A close-up view of the arm 50 of an exemplary embodiment of the present invention is schematically shown. The device is shown in a closed configuration. As previously described, the closed configuration is intended to gently hold the nerve 200 in the chamber where the double-sided electrode 194 is located. The advantage of this gentle holding force is to maintain direct contact with the nerve 200 on the wall 66 or floor 65 of the chamber 101 where the electrode 104 is located, and to reduce the size of the channel 102 for smaller nerve 200 sizes. In some embodiments, the total height of the wall 66 from the bottom to the top of the channel can be 1400 μm. The shape and size of the electrode 104 can be a curved "L" shape to promote direct contact whether the nerve 200 is at the longer or shorter end of the size range.

[0163] The main protrusion 62 of the spring loaded retention arm 50 has two purposes: one, to provide a reduced width of the channel 102 to help secure the largest nerve 200 in the chamber 101 after the nerve moves down the channel 102; and two, to provide gentle resistance to the movement of the nerve 200 to keep it in the electrode 104. The angle of the protrusion 62 is angled to gently push the nerve 200 toward the electrode. In various embodiments, the length of the protrusion 62 can be 430 microns. The protrusion 62 can be paired with a double-sided or angled electrode 104 (see, for example, Fig.16 ) to accommodate the changing angle of the spring loaded fixed arm 50 as the size of the nerve changes. Smaller nerves 200 are pushed down into the horizontal portion of the electrode. As this angle changes with the size of the nerve, the largest nerves 200 are pushed more toward the vertical portion. The figure below lists the breakdown of angles and distances for nerves with diameters of 100 μm to 400 μm.

[0164] In various embodiments, the spring-loaded fixed arm 50 can be mainly composed of an elastic material (e.g., silicone or plastic). Various embodiments can form at least a portion (e.g., an outer coating) of the arm 50 by a material with a Shore A hardness of 30 to 50. In addition, although soft neural interface materials (e.g., silicone) are ideal, the spring-loaded arm 50 can have an overmolded or insert-molded component embedded in silicone to provide further spring force, especially in larger applications. Some options for this insert component are nitinol springs, stainless steel springs, other elastic materials or overmolded springs, and other similar materials with different hardnesses. In addition, various material layers with different elastic materials can also provide the required force. The material preferably has biocompatibility for long-term implantation. Some embodiments can form arms by silicone, polyurethane, embedded nitinol and / or stainless steel springs, etc.

[0165] The electrodes 104 may also include relief spaces 64 on both sides for nerve swelling. The nerve 200 is flexible and acts more like a water balloon than a cable. If the nerve 200 is traumatized during implantation, it swells and uses the relief spaces 64 to expand so as not to experience enough pressure to cause further damage. During swelling, or in the event that temporary swelling exceeds the ability of the clamp to accommodate changes in nerve size, there are one or more relief spaces 64 for the nerve to expand to ensure that the nerve is not further damaged. The relief spaces 64 provide a relief area for any swelling or pressure buildup without affecting the electrode-nerve contact.

[0166] Fig.12 Multiple orientations of the device body and channel / chamber orientations of exemplary embodiments of the present invention are schematically shown. The orientation of the channel 102 and chamber 101 can be horizontal, vertical, or at any angle relative to the housing 48 / body 40 of the neuromodulator. In addition, the channel 102 and chamber 101 can be located at the center or one end of the body 40 as needed to meet various anatomical requirements. Alternatively, some embodiments can separate the channel / chamber structure from the body 40 of the implant and use it at the end of the wire or wire extension to improve the implantation time of conventional neurostimulators.

[0167] Fig.13 A device having a plurality of electrodes 104A-104D and chambers 101A-101D is schematically shown in accordance with an exemplary embodiment. The various chambers 101A-101D may accommodate nerves 200 of various sizes. Fig.13 Also shown are different orientations of the channel 102 relative to the device body 40. A double-sided electrode 104A-104D may be located in each chamber 101A-101D.

[0168] Having a series of channels 102A to 102D and chambers 101A to 101D (e.g., gradually getting smaller) facilitates the stretched nerve 200 to enter the appropriate chamber 101A to 101D according to the size of the nerve. This arrangement accommodates a wider range of nerve sizes. The increasing protrusions provide a force to press the nerve 200 into the electrode located in the chamber, but also prevent or inhibit larger nerves from passing through the smaller chamber 101, while preventing or inhibiting the relaxed nerve from leaving the chamber where it is currently located. In addition, or alternatively, some embodiments may include a flap or latch (e.g., at the entrance of the channel 102 or the entrance of the chamber 101) to further secure the nerve in the chamber. The flap (not shown) can be made of silicone to keep the device in a closed state. The latch or fixing feature can be a latch or fixing feature added to the open end.

[0169] The apparatus 100 and the signal generator may be distributed separately or together as a kit.

[0170] Obviously, various embodiments provide many advantages. For example, originally easy to infiltrate liquid and biocompatible electronic components are reliably separated from aqueous in vivo implantation environment. In addition, encapsulation body 46 and / or housing 48 are formed by the material selected for transmitting RF energy. The housing 48 of silicone overmolding allows the manufacture of complex shapes. Silicone can be processed at a higher temperature than the electronic device originally withstands (for example, if they are to be injection molded). In various embodiments, device 100 has a reliable airtight package, and has a desired (for example, complex) external geometry and hardness to contact with tissue (for example, nerve 200) in the body.

[0171] As another example, exemplary embodiments are easy to implant, i.e., the nerve only needs to be slid into the chamber with minimal force. Exemplary embodiments also reduce surgical time, avoid trauma, can be implanted in a smaller space, and cause minimal changes to the tissue relative to typical electrode cuffs. In addition, exemplary embodiments can be suture-free (i.e., no complex sutures are required to secure the nerve - easy to deploy). In addition, the direction and orientation of the gentle force of the arm 50 promotes direct contact with the nerve, resulting in the electrical signal being directly close to the nerve, reducing power consumption, maximizing stimulation, and reducing tissue ingrowth between the nerve and the electrode, thereby reducing signal attenuation.

[0172] Typically, the pressure to position the largest size nerve within the chamber is well below the generally accepted acute limit of 30 mmHg for the largest nerve within the design window. In some embodiments, the cross-sectional size (e.g., diameter) of the nerve can be about 0.5 mm to about 3.0 mm. However, various embodiments can accommodate larger nerves or even smaller nerves. The holding force pressure is also well below the generally accepted chronic limit of 20 mmHg for the largest nerve within the design window. To confirm this, the inventors performed various tests. The pressure of the device on the nerve was performed on a 10X scale model. The pressure sensor was combined with a phantom nerve filled with fluid. The nerve was inserted and removed from the device, and the maximum pressure and holding pressure were recorded (the insertion of the nerve was the worst case, without manually opening the clamp, but the nerve was subjected to the full pressure of the clamp when inserted). The maximum force recorded was 15 mmHg and the maximum holding force recorded was 3.1 mmHg.

[0173] Fig.14 Detail of the protrusion 62 on the arm 50 of an exemplary embodiment is schematically shown. As the size of the nerve changes from 100 μm to 400 μm, the angle of the protrusion 62 on the spring loaded fixed arm can be changed to accommodate the larger size difference. The calculations for 100 μm to 400 μm are shown below and can be adjusted for other nerve ranges. The examples provided below assume the following:

[0174] The channel in the open configuration has a width of 300 μm when fully opened,

[0175] Raised features in the channel are slightly larger than the maximum configuration size of 430 μm,

[0176] The electrodes are 450 μm in both vertical and horizontal directions.

[0177] The total height of the channel and chamber is 1.4 mm.

[0178] Distance between electrode and corner (e): 0.13mm

[0179]

[0180] Figures 15 to 17 Various details of the electrode 104 of an exemplary embodiment of the present invention are schematically shown. The electrode 104 in question can have horizontal planes and vertical surfaces to accommodate various angles of engagement of the pressing portion of the arm 50 with the nerve. The surface area of ​​the electrode 104 is preferably adapted to the desired charge density on each face of the electrode 104. Fig.15 The curved electrodes of an exemplary embodiment are schematically shown.It should be apparent that the above dimensions are exemplary only.

[0181] Fig.15 An angle electrode conforming to exemplary dimensions is schematically shown. The angle between the two portions of the angle electrode 104 can be adjusted. The bent or folded electrode can provide better direct contact with the nerve than a conventional one-dimensional electrode. Since the angle of pressure on the nerve varies with the size of the nerve, flexibility is provided so that both horizontal and vertical directions can be in close contact with the conductive surface. Alternatively, in different directions, the double-sided electrode can be configured not only in an "L" shape, but also in various internal angles to accommodate different electrode orientations. Fig.17 The folded electrode 104 of an exemplary embodiment is schematically shown. The folded electrode 104 is configured such that both sides of the electrode extend to both sides of the nerve, "sandwiching" the nerve between the two sides of the electrode.

[0182] Figures 18A to 20C Other embodiments of the neuromodulation device 100 according to an exemplary embodiment are schematically shown. Specifically, Figures 18A to 20C Embodiments having multiple jaws 50 (e.g., formed of silicone or including silicone overmolding as discussed previously) are shown. The body 40 is omitted in some of the figures, but it should be understood that various embodiments may include the body 40, the housing 48 (e.g., ceramic), and / or other components previously described. However, in contrast to the previously shown embodiments in which the direction of the passage 102 opening is substantially perpendicular to the body 40, Figures 18A to 20C An embodiment is shown where the channel 102 opens substantially parallel to the longitudinal axis of the body 40. However, in other embodiments, the channel 102 may be oriented in any direction (e.g., diagonally from the body 48). It should also be understood that the direction relative to the body may depend on the orientation and size of the body.

[0183] In some embodiments, the jaws are directly coupled to the body 40. Thus, the chamber is at least partially formed by the body 40 (e.g., by the enclosure 46 and / or a housing surrounding the enclosure 46). Alternatively, the jaws 50 may be separately coupled to the body via an attachment portion. For convenience, Figures 18A to 20C The body 40 and the housing 48 are not shown in FIG. 4 , but it should be understood that various embodiments of the jaws 50 may be coupled to the housing 48 and / or the enclosure 46 .

[0184] Advantageously, a single device 100 is configured to couple to and stimulate nerves 200 of various sizes (eg, 0.5 mm to about 4 mm).

[0185] although Fig.18A4. The body 48 is shown as being smaller than the jaws 50, but it should be understood that the figure is not necessarily drawn to scale. In some embodiments, the body 48 can be larger or smaller than the jaws 50. In addition, in various embodiments, the body 48 can form a portion of the chamber 101 having the electrodes 104. However, in other embodiments, the body 48 may not form a portion of the chamber 101. Instead, the jaws 50 and / or an intermediate between the jaws 50 can define the chamber 101.

[0186] Figures 18A to 18C The process of positioning a small nerve 200 (eg, about 0.5 mm to about 1.5 mm in diameter) within chamber 101 for stimulation is schematically illustrated. A side view of device 100 is shown.

[0187] To facilitate discussion, Figures 18A to 18C The nerve shown in the figure is a small nerve with a diameter of about 1 mm. The jaws 50 together define a V-shaped funnel 68 on the outside of the device 100, which is configured to help the surgeon position the nerve 200 at the proximal end 72 of the channel 102. When the nerve 200 is located at the proximal end 72 of the channel 102, the cross-sectional dimension of the nerve 200 is preferably larger than the channel 102. For example, the cross-sectional dimension of the channel 102 can be about 0.45 mm to about 0.75 mm. However, in some embodiments, the channel 102 can be completely closed (e.g., with a dimension of about 0 mm). Advantageously, the reduced channel size 76 prevents the nerve 200 from accidentally shifting. In addition, to this end, the channel 102 can have a nonlinear or tortuous shape to help prevent the nerve 200 from accidentally shifting. Therefore, various embodiments may require medical personnel to apply force in at least two different directions to pass through the channel (when inserting and removing the nerve). However, some embodiments may include a linear channel 102.

[0188] In any case, if Fig.18B As shown, the nerve 200 can be stretched (e.g., by a surgeon applying force) and / or squeezed (e.g., by the inner surface of the channel 102) to reduce the cross-sectional size of the nerve 200. Preferably, the reduction in size of the nerve 200 is less than 50% to prevent or reduce damage to the nerve 200 caused by excessive reduction in cross-sectional size. For example, a 1 mm nerve 200 can be reduced to a cross-sectional size of approximately 0.75 mm. Assuming that the channel size 76 is approximately 0.5 mm, the nerve 200 may still be too large to pass through the channel 102. To this end, the device 100 may include a hinge 78 that allows the jaws 50 to open, thereby expanding the channel size 76. In some embodiments, the hinge 78 is formed of a deformable material (e.g., silicone), allowing the jaws 50 to open outward. In addition, or alternatively, the channel 102 can include a deformable and / or elastic wall or coating that is used to expand the channel size 76.

[0189] like Fig.18C As shown, when the nerve 200 passes through the distal end 74 of the channel 102 and enters the chamber 101, the jaws 50 can be closed again. Due to the reduction in channel size 76 and the non-linear channel 102 shape, the small nerve 200 can be securely coupled within the chamber 101. Although not drawn to scale, the jaws 50 can include a nerve contact surface 58 that is configured to press and / or hold the nerve 200 against the electrode 104. In various embodiments, the jaws 50 are biased to return to the closed position, and / or the deformable material can be resilient and return to its original size.

[0190] Fig.18D A perspective view of the device 100 is schematically shown (details of the chamber 101, such as the electrodes 104, are omitted). The channel 112 has a specific movement path 113 (also referred to as the central axis 113) for the nerve 200. For example, Fig.18D As shown, the central axis 113 is non-linear. The central axis 113 may be defined by the arm 50.

[0191] In addition to the central axis 113, the device 100 also has a longitudinal axis 112 that is orthogonal to the central axis 113 at any given point. During nerve implantation, the nerve 200 is generally parallel to the longitudinal axis 112 as it moves along the central axis 113. Two different longitudinal axes 112A and 112B are shown at two different points along the central axis.

[0192] Fig.18E Schematically shows Fig.18D 1. A cross-sectional view of the longitudinal axis 112A of the jaws 50. As shown, the channel 102 is axial so that the longitudinal axis 112A is uninterrupted. The nerve 200 passes through the channel 102 with minimal manipulation by the surgeon. In some embodiments, the nerve 200 can be stretched to pass through the channel 102 and / or the channel wall formed by the jaws 50 can be deformable. Figure 18G A nerve passing through channel 102 is schematically shown at a cross section of shaft 112A.

[0193] Fig.18F Schematically shows Fig.18D A cross-sectional view along the longitudinal axis 112B. Fig.18F Shown with Fig.18D However, again, the channel 102 is axial, so that the longitudinal axis 112B is uninterrupted. It can therefore be said that the channel is continuously axial, that is, the longitudinal axis 112 at any given point along the central axis 113 is uninterrupted.

[0194] Fig.18H Schematically shows Figures 18E to 18GIn another embodiment, the longitudinal axis 112C is interrupted (e.g., by the tooth 151). In order to allow the nerve 200 to pass through Fig.18H To remove the channel 102, the surgeon must very carefully manipulate the nerve 200 (e.g., conform it to the shape of the shaft 112C), force the nerve through by applying traumatic pressure, or actively open the jaws 50 (e.g., using a separate tool). Fig.18H There is no axial longitudinal axis 112C at rest (as shown), but when jaws 50 are opened, longitudinal axis 112C may become axial. However, exemplary embodiments advantageously have axial longitudinal axes 112A, 112B at rest so that the nerve can easily slide into chamber 101.

[0195] Therefore, if Figures 18D to 18F As shown, some embodiments have a continuous axial non-linear channel 102 (ie, along the central axis 113). Advantageously, nerves can be passed through the channel 102 with minimal manipulation and without trauma, and without the need for a separate tool to open the arm 50.

[0196] Figures 19A to 19C The process of positioning a medium sized nerve 200 (eg, about 1.5 mm to about 2.5 mm in diameter) within chamber 101 for stimulation is schematically illustrated. A side view of device 100 is shown.

[0197] To facilitate discussion, Figures 19A to 19C The nerve 200 shown in is a medium nerve having a diameter of approximately 2 mm. Similar to the previous process, the V-shaped funnel helps to position the nerve 200 at the proximal end 72 of the channel 102. For ease of discussion, the nerve 200 can be stretched to reduce the nerve diameter to approximately 1.5 mm. As previously discussed, the channel dimension 72 can be approximately 0.5 mm. Therefore, when the jaws 50 are in the resting position, the nerve is much thicker than the channel 102. The jaws 50 can be opened to increase the channel dimension 76 and allow the nerve 200 to pass through the channel. To this end, an exemplary embodiment can include a delivery device having a cam feature that can press the jaws 50 open by deformation and / or articulation. Although Fig.18B The hinge split is schematically shown, but various embodiments do not have a hinge opening (which could otherwise trap a portion of a larger deformed nerve).

[0198] like Fig.19CAs shown, with nerve 200 in chamber 101, jaws 50 can be reclosed. For example, nerve 200 relaxes and returns to its 2 mm diameter. In addition, the silicone of jaws 50 can relax and channel size 76 returns to approximately 0.5 mm, thereby preventing the nerve from backing out of channel 102. In some embodiments, jaws 50 are biased to a resting position (e.g., a position in which channel 102 dimension 76 is approximately 0.5 mm or fully closed). In addition, or alternatively, the delivery device can close jaws 50. The silicone deformation and small Z channel 102 ensure that the medium-sized nerve is firmly coupled in chamber 101.

[0199] Figures 20A to 20C The process of positioning a large nerve 200 (e.g., having a diameter of about 2.5 mm to about 3.5 mm) within chamber 101 for stimulation is schematically illustrated. A side view of device 100 is shown. Fig. 20A As shown, the device 100 is considered to be in a resting or resting position. In the resting position, the device is in a stable state, that is, no force is applied to the device to open the jaws 50 (e.g., by a nerve or tool). Therefore, in various embodiments, the resting position is the "closed position" of the device. As previously described, the closed position does not mean that the channel or chamber needs to be closed. In fact, as shown in the figure, in various embodiments, the device has an open channel 102 when at rest. In addition, when the device is in a resting state (and when the device is converted to its open configuration), the channel 112 can be continuously axial. Some embodiments can close the channel (e.g., using a flexible flap or valve with a very low opening pressure). This closure can be applied to the channel 102 without limiting the ability to use the sliding lock nerve positioning method.

[0200] To facilitate discussion, Figures 20A to 20C The nerve 200 shown in is depicted as a large nerve having a diameter of about 3 mm when undeformed. As previously described, the nerve 200 can be located at the proximal end 72 of the channel. The device 100 can have a chamber size 83A (e.g., a maximum chamber size or a minimum chamber size) in which the nerve 200 is not present.

[0201] like Fig. 20BAs shown, the nerve 200 can be moved along the central axis 113 of the channel. In some embodiments, the nerve 200 is stretched (e.g., by a surgeon) and / or squeezed (e.g., by the inner surface of the channel 102) to reduce the cross-sectional size of the nerve 200. Preferably, the reduction in size of the nerve 200 is less than 50% to ensure the safety of the nerve 200, as a greater reduction in the cross-sectional size can cause some damage. For example, the nerve can be reduced to a cross-sectional size of about 2.25 mm. Assuming that the channel size 76 is about 0.5 mm, the nerve 200 may still be too large to pass through the channel 102. To this end, the hinge 78 opens the jaws 50 and expands the channel 102 size 76, thereby allowing the large nerve 200 to pass through the channel 102. Therefore, various embodiments have a chamber 102 of adjustable size and / or shape. Similarly, the chamber size 83B can be adjusted by movement of one or more arms 50.

[0202] like Fig. 20C As shown, when the nerve 200 passes through the distal end 74 of the passage 102 and enters the chamber 101, the jaws 50 can be closed again. However, due to the large size of the nerve 200, the jaws 50 may or may not be able to fully close and return the passage 102 to its original size 77. Similarly, the arms 50 may or may not be able to fully close and return the chamber 101 to its original size 83A. When the nerve 200 is located in the chamber 101, the chamber 101 can have a new adjusted chamber size 83C. Regardless, the jaws 50 retain the large nerve 200 within the chamber 101. To this end, the jaws 50 can include relief spaces 64 (also referred to as deformation regions 64), wherein the shape of the nerve 200 can deform and expand when compressed (e.g., so that the cross-sectional area of ​​the nerve is not reduced as it would be without the deformation regions 64). In various embodiments, the nerve 200 can deform and / or expand in one or more relief spaces 64, thereby reducing the pressure applied to the nerve. The device can be configured to allow for nerve free space 64, with the pressure applied to the nerve being less than 4 kPa. Additionally, to help reduce the pressure applied to nerve 200, contact surface 58 can be configured to deform, thereby providing additional space for nerve 200 to expand within chamber 101. Additionally, in some embodiments, such as Fig. 20C As shown, the dimension 76 of the channel 102 in the resting configuration may be expanded due to interference with the greater nerve 200 .

[0203] Due to the reduction in channel dimension 76 and the non-linear channel 102 shape, a small nerve 200 can be securely coupled within chamber 101. Although not drawn to scale, jaws 50 can include a nerve contacting surface 58 configured for pressing and / or holding nerve 200 against electrode 104.

[0204] It should be appreciated that various embodiments advantageously allow nerve 200 to expand / deform within chamber 101, rather than compensatory expansion / deformation which may occur outside of chamber 101 and damage nerve 200. However, in various embodiments, some deformation may occur outside of chamber 101. Preferred embodiments advantageously provide deformable nerve contacting portions of the jaws, as well as designated relief spaces 64 within the device to allow deformation near / local to the area of ​​nerve compression. As is known in the art, nerves are comprised of bundles of axons. By allowing local deformation of the nerve, the position of individual axons and / or bundles may be rearranged without necessarily damaging any individual axons (as would occur if the nerve were sharply compressed or stretched).

[0205] Fig.21 and 22 A neuromodulation device 100 is schematically shown in accordance with an exemplary embodiment. Fig.21 Four different views of the neuromodulation device 100 are shown. The hermetically sealed body 40 is largely omitted. However, a feed-through conductor 80 extending from the interior of the hermetically sealed body 40 is shown. The feed-through conductor 80 extends through the encapsulation body 46 and the buffer layer 49. The feed-through conductor 80 then forms an electrode 104 within the chamber 101 defined by the movable arm 50.

[0206] The movable arm 50 is shown biased toward a closed position. Although referred to as a "closed position", some embodiments may have a gap 76. Therefore, the movable arm 50 does not necessarily have to completely close the gap 76 in the closed position. The closed position 76 is used to refer to a position of the passageway 102 that is narrow enough to retain a nerve. As the nerve passes through the passageway 102, the gap 76 increases (e.g., because the arm 50 moves and / or deforms), and the movable arm 50 transitions to an open position. To help facilitate the opening of the passage, the movable arm 50 may include one or more bend points 81 formed of a material configured to bend so as to accommodate the nerve 200. It should be understood that the gap 76 does not need to be completely closed to be biased toward the closed position. Similarly, the gap 76 does not need to be completely open to transition to an open position.

[0207] As previously described (e.g., see Figures 18A to 18G), the device 100 defines an axial channel along the length of the channel 102. Advantageously, the continuous axial channel 112 allows for easy insertion and / or removal of the nerve 200, particularly using the sliding lock method described in U.S. Patent Application No. 16 / 414,169, the entire contents of which are incorporated herein by reference. Some embodiments may use a non-axial channel 112 so that the longitudinal axis of the channel 112 changes direction along its length (e.g., the interlocking teeth in FIG. 18). However, embodiments having an axial channel 112 may advantageously use a sliding lock method, for example, by axially stretching the nerve 200 and sliding it through the continuous axial channel 102. This method advantageously does not require the use of external tools or other forces (other than the pressure of the nerve pressing on the jaws 50) to help open the jaws 50 to allow the nerve to pass through the channel 102.

[0208] Fig. 22 Four different views of alternatives of the movable arm 50 are shown according to an exemplary embodiment. Fig. 22 A curved feature 81 is shown that is configured to move a larger nerve 200 as it passes through the channel 102 and / or sinks into the chamber 101. However, the curved feature 81 (e.g., neck) helps to keep the smaller nerve 200 pressed against the electrode 104. Advantageously, the neck 81 allows the head 82 to pivot to accommodate various sized nerves 200 in the channel 102 and / or chamber 101.

[0209] In some embodiments, the feed-through conductor 80 is welded to a separate electrode 104 at a welding point outside the hermetically sealed package 46. However, various embodiments provide a seamless (e.g., unwelded) electrode 104 formed by the feed-through conductor 80. The tolerance of welding the electrode 104 to the feed-through pin 80 at this scale is difficult. By using a seamless electrode 104, the manufacturing problem is simplified. In addition, as shown, a portion of the electrode 104 can be embedded in the arm 50. Therefore, the electrode 104 can have an exposed electrode portion 104A and an embedded electrode portion 104B. For example, the embedded portion 104B can include the end of the electrode. In various embodiments, the exposed electrode portion 104A is configured to contact at least 20%, at least 25%, or at least 35% of the circumference of the nerve 200 located in the chamber 101. In some embodiments, the exposed electrode 104A is configured to contact at least 40% of the circumference of the nerve 200 located in the chamber 101.

[0210] As shown, various embodiments combine the neural coupling portion (i.e., chamber 101) and the implantable pulse generator (e.g., within the package 46), advantageously providing a smaller device 100 and a simpler implantation procedure. In addition, various embodiments do not require external wires between the neural coupling portion and the IPG. Advantageously, a single seamless feedthrough conductor 81 can extend from the hermetically sealed housing 46 into the chamber 100 to form the electrode 104. This is in contrast to a device in which the feedthrough conductor 81 is welded to the electrode 104. Exemplary embodiments can use the feedthrough conductor directly as the electrode 104, thereby providing a seamless or continuous electrode.

[0211] The method of implanting an IPG with prior art devices is to expose the nerve to place the cuff, then use a custom tool to tunnel the wire to the location of the IPG, where a pocket is formed under the skin to place the IPG. The IPG is then connected to the wire and placed in the pocket. In contrast, the exemplary embodiment provides a simpler process because the size is automatically adjusted to the nerve (within about + / - 50% to 75% of the acceptable range, for a 2mm nerve, the range is 0.5mm to 3.5mm). Advantageously, there is no tunnel and no need to set up a separate surgical site for the IPG.

[0212] In addition, the entire lead body and connector block, proximal connector and other similar components are not required. The feed-through conductor 81 (e.g., extending from the hermetically sealed package 46) can be used as the electrode 104. The feed-through conductor 81 can be formed of, for example, a Pt-Ir material. Another advantage of using this structure as the electrode 104 is that the feed-through pin 81 can be bent and used to support the structure and retention force of the movable arm 50, thereby non-invasively coupling the nerve 200.

[0213] Thus, the exemplary embodiment provides a neuromodulation device in which the feedthrough conductor 81 serves as both an electrode 104 and a structural component, which together achieve the appropriate bending characteristics of the arm 50. The selection of material properties allows the nerve 200 to maintain close contact with the electrode 104 without causing trauma.

[0214] The movable and / or flexible arm 50 can be adjusted both during nerve insertion into the channel 102 and while the nerve is in the chamber 101. The arm 50 is configured to adjust the size of the chamber 101 to capture smaller nerves (e.g., 0.5 mm, 1 mm) without applying traumatic pressure to larger nerves 200 (e.g., 3 mm, 4 mm).

[0215] Exemplary embodiments are configured to hold nerves of 0.5 mm to 4 mm in size in chamber 101 at a pressure of less than 6.7 kPa. Nerve 200 is relatively susceptible to high pressure damage. Therefore, exemplary embodiments form arm 50 from a material that biases the arm to reduce the pressure on nerve 200 as it passes through channel 102 and stays in chamber 101. Specifically, arm 50 is configured to apply a pressure of less than 6.7 kPa to nerve 200 to prevent structural damage to the nerve. For example, the bursting pressure of channel 102 is preferably less than 6.7 kPa. In various embodiments, device 100 is configured so that the pressure applied to the nerve is less than 10 kPa or less than about 1.5 psi. Of course, some embodiments can provide higher pressures than those disclosed herein. Based on the time that nerve 200 stays in channel 102, the pressure can be reduced. For example, if it takes 2 minutes or more for the nerve to pass through channel 102, device 100 should be configured to apply a pressure of less than 6.7 kPa to the nerve. Likewise, the nerve 200 is located in the chamber for a long period of time, and therefore, the device can be configured to apply less than 4 kPa of pressure to the nerve at any given time in the chamber. The device 100 can be configured to generate these pressures using specific materials, relief spaces 64, and / or multiple arms 50, etc.

[0216] In addition, the exemplary embodiment is configured to maintain a nerve 200 having a size of 0.5 mm to 4 mm at a pressure of 4 kPa (or 30 mm Hg) in the chamber 101 to reduce undesirable long-term effects, such as nerve dysfunction and / or edema. Therefore, the chamber 101 preferably has a holding pressure of less than 4 kPa for a nerve 200 having a diameter of 1 mm to 3 mm (nerve diameter is a generally accepted measurement of nerve size when the nerve is at rest and undeformed).

[0217] Bench testing of device 100 showed that the maximum insertion force for large nerves (e.g., 4 mm diameter nerves) was less than 2 kPa (15 mm Hg), and the average compression force after the model nerve was placed in the chamber was 0.147 kPa (1.1 mm Hg), indicating that the flexible channel / chamber solution is a feasible solution.

[0218] In addition, some electrodes implanted in nerves in clinical studies chronically compress the nerve (approximately 40%). These electrodes, referred to as “flat” electrodes (primarily FINE electrodes), have been reported to estimate intrafascicular pressures below 30 mm Hg to reshape the nerve without significantly altering nerve physiology or histology. Flattening a nerve to greater than 60% produces a pressure of 60 mm Hg and can result in nerve damage. As described in the previous paragraph, early bench testing of the NeuroClip has shown that chronic pressure values ​​much lower than the 60 mm Hg shown with the “flat” electrodes can be achieved.

[0219] Exemplary embodiments provide a neuromodulation device configured to non-invasively couple to various nerve sizes ranging from 0.5 mm to 4 mm. As described herein, the non-invasive coupling provides a sustained pressure of less than 4 kPa to the nerve while the nerve is in the chamber (e.g., staying in the chamber for hours, days, etc.). In addition, the non-invasive coupling provides a pressure of less than 6.7 kPa when passing through the channel 102 (e.g., passing through the channel for a short period of time, less than 1 minute).

[0220] The device 100 is configured to accommodate various nerve sizes (eg, from 1 mm to 3 mm). The same approach can be extended to a variety of nerve size ranges.

[0221] To accommodate a variety of nerve sizes, the device is flexible enough to allow the largest nerves to pass through the channel portion and remain in the chamber, but not so large that the smallest nerves can easily slip out while in contact with the electrodes. To this end, various embodiments use silicone from Nusil (a product of NUSIL with Class VI biocompatibility certification), a biomaterial widely used in long-term active implantable devices. This material bends to accommodate the largest nerve passing through the channel 102 and, when the nerve is in the chamber, reshapes to the additional space provided to prevent pressure buildup inside the nerve. The greater teres major nerve is not overly compressed in the chamber, but instead changes shape to fill the open space provided. The nerve 200 can withstand moderate reshaping of the cross-sectional shape without causing damage (e.g., a 30% reduction in maximum cross-sectional area).

[0222] Figures 23A to 23C A neuromodulation device according to an exemplary embodiment is schematically shown. Fig.23A A 1 mm nerve is shown pressing against the arm 50 and the protrusion 54. In some embodiments, the arm 50 is movable and deflects in response to pressure from the nerve. Additionally, or alternatively, the arm 50 and / or the protrusion 54 are formed of a deformable material (e.g., a cushioning layer) that deforms to expand the channel gap. In other embodiments, the arm 50 may be static. Fig. 23B The nerve is shown deforming to pass through the continuous axial channel 102. Finally, Fig.23C The position of the nerve 200 relative to the electrode 104 is shown. Unlike the static arm 50, the exemplary embodiment of the movable arm 50 can provide a contact pressure to the nerve 200 that pushes the nerve 200 into contact with the electrode 104.

[0223] Fig.23C The nerve shown in is a relatively small nerve (e.g., 1 mm in diameter). Larger nerves (e.g., 3 mm in diameter or more) deform to match the available space in chamber 101 without applying traumatic pressure to the nerve after remodeling. Figures 23D and 23E schematically illustrate a large nerve changing its cross-sectional shape, but maintaining its cross-sectional area.

[0224] In addition, the small nerve 200 is held in the chamber very close to the electrode 104, ensuring that the stimulation amplitude can be kept low and maintaining signal efficiency. The inventors tested large nerves (e.g., 3 mm or more) using a device with a movable arm 50 and found that after placing them in the chamber, the pressure was less than 5 mmHg.

[0225] Clearly, the exemplary embodiments provide the advantages of a single device that can couple and reliably stimulate a variety of different sized nerves. In addition, the device can reliably hold nerves of different sizes (e.g., a small diameter of 0.5 mm to a large diameter of 4 mm) without causing undue compression / trauma to the nerve 200. In fact, the chamber 101 (e.g., a portion of the movable arm 50) adjusts to help hold the nerve.

[0226] Various embodiments use a combination of epoxy and medium durometer silicone (e.g., 60 to 90 Shore A), with or without additional structural components. For example, epoxy can be used to support feedthrough conductors to minimize bending strain points. Feedthrough conductors (e.g., Pt-Ir, gold, Nitinol, or similar materials) are bent and bonded to the head structure to provide additional structural support and retention. The feedthrough or connected electrodes are then embedded in a medium to low durometer silicone portion (typically 30 to 50 Shore A) that has the positioning and resistance required to achieve nerve retention without causing damage to the nerve. The structure is different from a conventional nerve because, in extreme cases, the cuff requires both the nerve and the cuff to deform in order to "slide" the nerve through the channel and into the chamber. By utilizing the natural stretching ability of the nerve and the slight movement of the silicone or wire arms of the device, acute pressure on the nerve can be minimized, even in cases where the nerve is 50-75% larger than the maximum size. Additionally, by minimizing internal nerve pressure by utilizing the ability of the largest nerve to adjust and redistribute its structure at minimal resting or ultimate force, there is ample room in the chamber for the nerve to relax, achieving a resting pressure well below the 60% compression known to cause injury.

[0227] For the smallest nerves, the “arm” portion of the device deforms less to achieve the same movement through the channel. In the chamber, significant deformation is required, but the structure of the feedthrough flexures as electrodes provides ample opportunity to maintain close connection between nerve and electrode, thus minimizing the impact on signal strength.

[0228] Therefore, in various embodiments, the channel 102 and / or chamber 101 is formed of a material configured to deform in response to non-traumatic pressure (e.g., less than 6.7 kPa) from the nerve. In addition, the channel 102 and / or chamber 101 is configured to change size due to one or more movable arms 50.

[0229] Among other advantages, the continuous axial channel 102 of the exemplary embodiment facilitates installation of the nerve into the chamber and removal of the nerve from the chamber 101. The channel 102 may also be non-linear to help keep the nerve within the channel (so that it is less likely to slide out of the continuous axial channel). The continuous axial channel 102 also helps reduce trauma to the nerve 200 during installation and removal. To further help reduce trauma, the device may include one or more bend points 81 that are configured to bend or pivot to accommodate nerves of various shapes and sizes. These features work together to allow the nerve to slide through the channel and / or push and / or deform the arm 50 to allow the nerve to pass through.

[0230] It should also be apparent that in various embodiments, one or more arms 50 define the dimensions of chamber 101 and / or channel 102. Arms 50 also provide a non-invasive force to deflect nerves 200 of various sizes toward electrode 104 such that the electrode contacts at least 20%, at least 25%, or at least 35% of the circumference of nerve 200. In various embodiments, particularly for larger nerves (e.g., 3 mm or more), electrode 104 contacts at least 60% of the circumference of the nerve when nerve 200 is located in chamber 101. Thus, device 100 advantageously non-invasively accommodates nerves of various different sizes. In addition, one or more arms 50 facilitate continuous contact and electrical coupling with electrode 104 by providing a restrictive force to compress the nerve. In addition, exemplary embodiments couple the device to the nerve without the use of sutures and without the need for specialized tools, thereby allowing for easy removal of the device.

[0231] Although various embodiments describe a device for coupling and treating nerves having a diameter of about 0.5 mm to about 4 mm, it should be understood that such devices and methods can be extended to accommodate nerves of various different sizes. For example, one skilled in the art can use the disclosure herein to configure the device to couple larger nerves having a diameter of about 5 mm to about 8 mm. As another example, the device can be configured to couple nerves 200 having a diameter of about 0.2 mm to about 2 mm. These devices can be configured to couple various nerve sizes without damaging the nerve (e.g., by applying less than 4 kPa of pressure to the nerve).

[0232] Although various inventive embodiments are described and illustrated herein, a person of ordinary skill in the art will easily conceive of various other methods and / or structures to achieve the functions described herein and / or obtain the results and / or one or more advantages, and each of these changes and / or modifications is considered to be within the scope of the inventive embodiments described herein. More generally, it will be readily understood by those skilled in the art that all parameters, dimensions, materials and configurations described herein are exemplary, and the actual parameters, dimensions, materials and / or configurations will depend on the specific application to which the invention teachings are applicable. Those skilled in the art will recognize, or will be able to determine using only routine experiments, that the specific inventive embodiments described herein have many equivalents. Therefore, it should be understood that the foregoing embodiments are presented only by way of example, and within the scope of the attached claims and their equivalents, the inventive embodiments may be implemented in a manner different from that specifically described and required. The inventive embodiments of the present invention are directed to each individual feature, system, article, material, kit and / or method described herein. In addition, any combination of two or more such features, systems, articles, materials, kits and / or methods (if such features, systems, articles, materials, kits and / or methods are not mutually contradictory) is included within the scope of the invention of the present invention.

[0233] Various inventive concepts may be embodied as one or more methods, of which examples have been provided. The actions performed as part of a method may be ordered in any suitable manner. Thus, embodiments may be constructed that are performed in a different order than the illustrated order, including some operations that may be performed simultaneously, even though they are shown as sequential operations in the exemplary embodiments.

[0234] Although the subject matter contained herein has been described in detail for purposes of illustration, it should be understood that such detailed description is for this purpose only and that the invention is not limited to the disclosed embodiments, but rather is intended to cover modifications and other arrangements within the spirit and scope of the appended claims. For example, it should be understood that the invention contemplates that, to the extent possible, one or more features of any embodiment can be combined with one or more features of any other embodiment.

[0235] Other examples are also within the scope and spirit of the specification and claims. In addition, some of the above functions can be implemented using software, hardware, firmware, hard wiring, or any combination thereof. Features that implement functions can also be physically located in various locations, including distribution, so that parts of the functions are implemented in different physical locations.

[0236] Although the subject matter contained herein has been described in detail for purposes of illustration, it should be understood that such detailed description is for this purpose only and that the invention is not limited to the disclosed embodiments, but rather is intended to cover modifications and equivalent arrangements within the spirit and scope of the appended claims. For example, it should be understood that the invention contemplates that, to the extent possible, one or more features of any embodiment can be combined with one or more features of any other embodiment.

[0237] Other examples are also within the scope and spirit of the specification and claims. In addition, some of the above functions can be implemented using software, hardware, firmware, hard wiring, or any combination thereof. Features that implement functions can also be physically located in various locations, including distribution, so that parts of the functions are implemented in different physical locations.

Claims

1. A method for stimulating nerves, comprising: A neuromodulatory device is provided, the neuromodulatory device having: a body comprising a hermetically sealed housing containing electronic devices therein, and a buffer layer at least partially encapsulating the hermetically sealed housing, An arm formed of an elastic material, a passage through which a nerve passes, the passage being defined at least in part by the arm, the passage having a continuous axial longitudinal axis when at rest, a neural stimulation chamber, the chamber being defined at least in part by the arm, the neural stimulation chamber being configured to retain a nerve therein, and an electrode within the chamber; reducing a maximum cross-sectional dimension of the nerve to define a stretched nerve having a reduced cross-sectional dimension, the reduction in the maximum cross-sectional dimension being less than 50%; moving the stretched nerve along the central axis through the channel such that the pressure exerted on the nerve by the channel walls at any given point is less than 6.7 kPa; placing the nerve within the chamber and increasing the cross-sectional size of the stretched nerve; and Keep at least 20% of the nerve's circumference in contact with the electrode.

2. The method according to claim 1, further comprising: reducing a cross-sectional dimension of the nerve within the chamber to define a stretched nerve having a second reduced cross-sectional dimension, the reduction in the maximum cross-sectional dimension being less than 50% of the maximum cross-sectional dimension; The stretched nerve is moved along the central axis through the channel to remove the nerve from the device such that the pressure exerted on the nerve by the channel wall is less than 6.7 kPa.

3. The method according to claim 1, wherein: At least 20% of the circumference of the nerve is maintained in contact with the electrode such that a pressure of less than 4 kPa is provided to the nerve.

4. The method according to claim 1, wherein: The undeformed diameter of the nerve is between 0.5 mm and 4 mm.

5. The method according to claim 1, wherein: The cross-sectional area of ​​the nerve in the chamber is greater than 50% of the cross-sectional area of ​​the undeformed nerve.

6. The method according to claim 5, wherein: The cross-sectional area of ​​the nerve in the chamber is equal to the cross-sectional area of ​​the undeformed nerve.

7. The method according to claim 5, wherein: The chamber contains a nerve release space.

8. The method according to claim 1, wherein: The arm is movable between an open configuration and a closed configuration, the movable arm being biased toward the closed configuration such that the size of the chamber and / or the channel can be adjusted by movement of the arm.

9. The method according to claim 1, wherein: The arm has one or more curved portions so that the size of the chamber can be adjusted by bending the arm.

10. The method according to claim 1, wherein: The arm comprises a cushioning material configured to deform at a pressure less than 6.7 kPa, such that the size of the chamber and / or the channel can be adjusted by deformation of the arm.

11. The method according to claim 1, wherein: One or more arms form a continuous axial passage through which the nerve passes, the passage being at least partially defined by the arms, the passage having a non-linear central axis.

12. The method according to claim 1, wherein: The buffer layer is formed of silicone.

13. The method according to claim 1, wherein: The package is formed of glass, ceramic, alumina, zirconium and / or plastic.

14. The method of claim 1, further comprising a continuous feed-through conductor extending through the package body, buffer layer, and movable arm, the feed-through conductor forming the electrode.

15. The method according to claim 1, wherein: The buffer layer is formed of a material having a Shore A hardness of 30 to 50.

16. The method according to claim 1, wherein: A portion of the body and a portion of the arm defining the channel are covered by the buffer layer.

17. The method according to claim 1, wherein: The buffer layer covers about 20% to about 99% of the neuromodulation device.

18. The method of claim 1 further comprising a second movable arm configured to transition between an open configuration and a closed configuration, the movable arm being biased toward the closed configuration, wherein: Movement of the second movable arm adjusts the size of the chamber and / or the size of the channel.

19. A neuromodulatory device comprising: A movable arm formed of an elastic material, the movable arm being configured to transition between an open configuration and a closed configuration, the movable arm being biased toward the closed configuration, the movable arm at least partially defining a chamber and a channel, the gap of the channel being less than 1 mm, the movable arm being configured to allow a nerve having a diameter of 1 mm to 3 mm to pass through the channel while providing a pressure of less than 6.7 kPa to the nerve, and the movable arm being further configured to apply a pressure of less than 4 kPa to the nerve when the nerve is stimulated by an electrode in the chamber.

20. The device according to claim 19, wherein The movable arm is configured to compress a nerve within the chamber to deform the nerve but to reduce a cross-sectional area of ​​the nerve by no more than 10%.

21. A method of controlling bladder function in a patient having symptoms (e.g., symptoms associated with overactive bladder (OAB) or stress urinary incontinence (SUI)) associated with a symptom signal (e.g., an OAB signal) generated by the patient's body, the method comprising: A neuromodulation device is provided, the neuromodulation device having a hermetically sealed enclosure and a movable arm, the enclosure and the movable arm being at least partially covered by a housing having a cushioning layer having a Shore hardness value softer than the enclosure, a passage defined by the body and the movable arm, the passage leading from an exterior of the neuromodulation device to a stimulation chamber having a stimulation electrode therein, the movable arm being capable of transitioning between a closed position and an open position; positioning the movable arm in an open position; After positioning the movable arm in the open position, positioning a designated somatic motor nerve of the coccygeal plexus and / or the perineal plexus associated with the pelvic floor within the chamber; After positioning the designated somatic motor nerve within the chamber, the movable arm is positioned in a closed position, the movable arm being configured such that a portion of the movable arm in contact with the designated somatic motor nerve is covered by the cushioning layer.

22. The method according to claim 21, wherein: The buffer layer is formed of silicone.

23. The method according to claim 21, wherein: The package is formed of glass, ceramic, alumina, zirconium and / or plastic.

24. The method according to claim 21, wherein: A feedthrough hole extends through the package body and the buffer layer.

25. The method according to claim 21, wherein: The buffer layer is formed of a material having a Shore A hardness of 30 to 50.

26. The method of claim 21, wherein: A portion of the body and a portion of the arm defining the channel are covered by the buffer layer.

27. The method of claim 21, wherein: The buffer layer covers about 20% to about 99% of the neuromodulation device.

28. The method of claim 21, wherein: The buffer layer has openings for electrodes and / or EMG.

29. The method according to claim 21, wherein: The buffer layer facilitates biasing of the movable arm.

30. The method of claim 21, further comprising: Clinical symptoms associated with certain forms of SUI and / or OAB are improved by transmitting modulatory signals to nerves via electrodes, the nerve signals being configured to activate the pelvic floor in a specified manner to restore damaged neuromuscular connections in SUI and block overactive sensory signals from the bladder to the spinal cord, thereby blocking urinary urgency symptoms.

31. The method of claim 21, wherein: The buffer layer is formed of a conformable material.

32. The method of claim 21, wherein: The designated somatic nerve is positioned within the chamber such that the designated somatic motor nerve is in contact with the electrode.

33. The method of claim 21, wherein: Positioning the movable arms in a closed position lightly compresses a designated somatic nerve within the chamber, wherein the light compression slightly deforms the nerve without causing damage.

34. The method of claim 21, wherein: The housing includes a protrusion configured to press against the movable arm in a closed position, the protrusion being configured to limit an amount of compression of the nerve by the movable arm.

35. The method of claim 21, wherein: The electrode partially surrounds the nerve.

36. The method of claim 21, wherein: The contact angle between the electrode and the nerve perimeter is less than 180 degrees.

37. The method of claim 21, wherein: The movable arm is biased toward a closed position.

38. The method of claim 21, wherein: The designated somatic motor nerve comprises the perineal nerve, further wherein the perineal nerve or pelvic floor nerve is part of the coccygeal plexus and / or the perineal plexus.

39. The method of claim 21, wherein: The transmitting includes generating a symptom control signal using a signal generator and transmitting the symptom control signal through an electrode, wherein the symptom control signal is transmitted using one or more wired or wireless communication media.

40. The method of claim 21, wherein: The amplitude of the symptom control signal is approximately 0.4 mA to 4 mA.

41. The method of claim 21, wherein: The symptom control signal is a periodic signal having a plurality of pulses, each pulse having a pulse duration of about 200 microseconds to 400 microseconds.

42. The method of claim 21, wherein: The symptom control signal is a periodic signal having a frequency of about 5 Hz to 20 Hz.

43. The method of claim 21, wherein: The transmission includes transmitting the symptom control signal in a single communication for no less than 10 minutes and no longer than 30 minutes.

44. The method of claim 21, further comprising transmitting a SUI control signal to the designated somatic motor nerve via the electrode, the SUI control signal having a frequency different from a frequency of the OAB control signal.

45. The method of claim 24, wherein: The SUI control signal is transmitted after the OAB control signal.

46. ​​The method of claim 24, wherein: The SUI control signal is configured to strengthen the pelvic floor when applied via the designated somatic motor nerve.

47. The method of claim 21, wherein: The SUI control signal is configured to strengthen or repair the pelvic floor.

48. A system for controlling bladder function in a patient having symptoms, such as symptoms associated with overactive bladder (OAB) or stress urinary incontinence (SUI), said symptoms being associated with symptom signals generated by the patient's body, said system comprising: a body at least partially covered by a buffer layer; a movable arm at least partially covered by the buffer layer, the body and the movable arm defining a passage therebetween, the passage leading from an exterior of the housing to the stimulation chamber; The movable arm is transitionable between a closed position and an open position such that the channel has a gap having a greater depth in the open position than in the closed position; an electrode located in the chamber, the electrode configured to couple with the perineal nerve, the electrode having a receiving interface configured to receive an OAB control signal for driving the perineal nerve; wherein the depth of the gap in the closed position is configured to be sufficiently small to inhibit non-destructive entry of nerves into the chamber, The depth of the gap in the open position is configured to be large enough to allow the perineal nerve to pass through.

49. The system of claim 48, wherein: The depth of the gap in the closed position is substantially zero.

50. The system of claim 48, wherein: The buffer layer is formed of silicone.

51. The system of claim 48, wherein: The package is formed of glass, ceramic, alumina, zirconium and / or plastic.

52. The system of claim 48, wherein: A feedthrough hole extends through the package body and the buffer layer.

53. The system of claim 48, wherein: The buffer layer is formed of a material having a Shore A hardness of 30 to 50.

54. The system of claim 48, wherein: A portion of the body and a portion of the arm defining a channel are covered by the buffer layer.

55. The system of claim 48, wherein: The buffer layer covers about 20% to about 99% of the neuromodulation device.

56. The system of claim 48, wherein: The buffer layer has openings for electrodes and / or EMG.

57. The system of claim 48, wherein: The buffer layer facilitates biasing of the movable arm.

58. An implantable neuromodulatory device comprising: a chamber configured to receive a nerve, the chamber having a cross-sectional chamber dimension; at least one electrode disposed in the chamber; as well as A non-linear channel having a proximal end and a distal end, the distal end terminating in the chamber, the non-linear channel having an adjustable channel inner dimension, the adjustable channel inner dimension defining a maximum channel inner dimension and a minimum channel inner dimension, wherein the chamber inner dimension is greater than the cross-sectional channel inner dimension.

59. The implantable neuromodulation device of claim 58, further comprising: A plurality of jaws define the non-linear channel.

60. The implantable neuromodulatory device of claim 59, wherein: The plurality of jaws at least partially define the chamber.

61. The implantable neuromodulator of claim 59, wherein: The jaws contain a nerve release space.

62. The implantable neuromodulator of claim 59, wherein: At least one of the jaws includes a hinge.

63. The implantable neuromodulatory device of claim 59, wherein: At least one of the jaws includes a deformable portion.

64. The implantable neuromodulatory device of claim 59, wherein: Each jaw includes a nerve contacting portion configured to compress a nerve having a diameter of about 1 mm to about 3 mm toward the electrode.

65. A method of stimulating a nerve, comprising: Provides nerves with resting nerve dimensions at rest; Providing an implantable neuromodulation device having a chamber configured to apply electrical stimulation or record neural activity, the chamber having a cross-sectional chamber dimension, the neuromodulation device having an adjustable channel, the channel having a maximum channel dimension and a minimum channel dimension, the minimum channel dimension being smaller than the cross-sectional dimension of the resting nerve; adjusting the channel size to be greater than 50% of the resting nerve size; positioning the nerve within the chamber by passing the nerve through the channel; Adjust the channel size so that it is less than or equal to 50% of the resting nerve size.

66. The method of claim 65, wherein: The neuromodulatory device comprises a plurality of jaws defining a channel size, wherein the jaws are movable and / or deformable.

67. The method of claim 65, wherein: The nerve has a diameter of about 1 mm to about 3 mm.

68. The method of claim 65, wherein: The channel defines a tortuous path.

69. The method of claim 65, wherein: The jaws contain a nerve release space.

70. The method of claim 65, wherein: The jaws include a nerve contacting portion configured to deform when contacting a nerve.

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