Systems and methods for neurostimulation

Abstract

The neuromodulation device includes a movable arm coupled with 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. The nerve stimulation chamber is at least partially defined by the movable arm. The nerve stimulation chamber is configured to hold a nerve therein. 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 chambers and channels are adjustable by movement of the arms in response to contact with the nerves. The channel may be continuously axial along a longitudinal axis of the channel when the movable arm is in the closed configuration. The chamber has an electrode.

Description

[0001] priority

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

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

[0004] Overactive bladder ("OAB"), which affects millions of people in the United States and worldwide, can lead to debilitating urgent and frequent urination, with or without urinary incontinence. Many in the field are puzzled by the fact that OAB is associated with nocturia, but there is no urinary tract infection or other obvious pathological conditions. The pathophysiology and etiology of idiopathic OAB are unclear, but it appears to be related to bladder detrusor dysfunction or detrusor overactivity. Current pharmacological treatments include oral antimuscarinics or oral β3-adrenergic receptor agonists. Such treatments have significant disadvantages in that they have limited efficacy and tolerability and cause 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, called "stress urinary incontinence" ("SUI"), occurs when urine leaks, where there is sudden pressure on the bladder and urethra, causing the sphincter to briefly open. With mild SUI, the pressure may come from sudden forceful activity, such as moderate exercise, sneezing, laughing, or coughing. However, if SUI is more severe, urine may leak with less forceful activities, such as standing, walking, or bending over. Urine "accidents" like these can range from a few drops of urine to enough to soak through clothing.

[0006] Those skilled in the art typically treat OAB and SUI with different treatment regimens. Summary of the invention

[0007] According to an embodiment, a neuromodulatory device includes a body having an airtightly sealed housing that contains an electronic device therein. The body has a buffer layer that at least partially encapsulates the airtightly sealed housing. A movable arm is connected 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. A neurostimulation chamber is at least partially defined by the movable arm. The neurostimulation chamber is configured to hold a nerve therein. The size and shape of the chamber can be adjusted by the arm moving 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 can be adjusted by the arm moving in response to contact with the nerve. When the movable arm is in the closed configuration, the channel can be continuously axial 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 passage. The movable arm can be configured to atraumatically retain a nerve having a stationary maximum cross-sectional dimension of 0.5 mm to 4 mm in the chamber when the movable arm is biased toward the closed configuration.

[0009] Among other things, the chamber may include one or more nerve relief spaces defined by the movable arm. The movable arm may also include one or more bending points. The distal end of the electrode may be embedded in the movable arm. A continuous feed-through 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 sized to contact 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 continuous axial.

[0011] According to another embodiment, a method for stimulating a nerve provides a neuromodulatory device. The device has a body, the body including an airtight sealed housing and a buffer layer, the airtight sealed housing containing electronic devices therein, the buffer layer at least partially encapsulating the airtight sealed housing. A movable arm is connected 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. A 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 can be adjusted by movement of the arm. The channel through which the nerve travels is at least partially defined by the movable arm. The size and shape of the channel can be adjusted by movement of the arm. The channel is continuously axial along the longitudinal axis of the channel. The device may include an electrode 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 is moved through the channel along the central axis of the channel. The nerve is positioned in the chamber and the cross-sectional dimension of the stretched nerve is increased.

[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 a hermetically sealed housing that houses electronics therein. The device has an arm formed of an elastomeric material. A channel through which the nerve travels 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 is moved through the channel along a central axis so that the channel wall applies a pressure of less than 6.7 kPa to the nerve at any given point. The nerve is positioned in the chamber and the cross-sectional dimension of the stretched nerve is increased. At least 20% of the circumference of the nerve is maintained in contact with the electrode.

[0014] In various embodiments, the nerve can have a different cross-sectional shape when 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 moved through the channel along the central axis to remove the nerve from the device such that the channel wall applies a pressure of less than 6.7 kPa to the nerve.

[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 nerve can have an undeformed diameter of 0.5 mm to 4 mm. The cross-sectional area of ​​the nerve positioned 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 arm can be moved between an open configuration and a closed configuration. The arm can be biased toward the closed configuration so that the size of the chamber and / or channel can be adjusted by movement of the arm. The arm can have one or more curved portions so that the size of the chamber can be adjusted by bending of the arm. The arm can include a cushioning material that is configured to deform at a pressure of less than 6.7 kPa so that the size of the chamber and / or channel can be adjusted by deformation of the arm. One or more arms can form a continuous axial channel through which a nerve travels. The channel can be defined at least in part by the arm. The channel can 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 body, the buffer layer and through the movable arm. The feed-through conductor may form an electrode. Thus, the electrode may advantageously be unsoldered / unjoined.

[0019] According to another embodiment, the movable arm is formed of an elastomeric 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 a chamber and a channel. The channel has a gap of less than 1 mm. The movable arm is configured to allow a nerve to pass through the channel for nerves having a diameter of 1 mm to 3 mm 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 nerve is stimulated by the electrode in the chamber.

[0020] The movable arm may be configured to press against a nerve in the chamber to deform the nerve but not to reduce the cross-sectional area of ​​the nerve by 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 is switchable between a closed position and an open position. The movable arm is positioned to the open position. After positioning the movable arm in the open position, a prescribed somatic motor nerve of the coccygeal plexus and / or perineal plexus associated with the pelvic floor is positioned within the chamber. After positioning the prescribed somatic motor nerve in the chamber, the movable arm is positioned to the closed position. The method transmits a symptom control signal (e.g., a SUI and / or OAB control signal) to the prescribed somatic motor nerve via an electrode. The control signal is configured to activate the pelvic floor in a prescribed manner to reduce the effects of the symptom signal on the spinal cord.

[0022] In some embodiments, a prescribed somatic nerve is located within the chamber and contacts the electrode. Positioning the movable arm in a closed position can compress the prescribed somatic nerve in the chamber, causing the nerve to deform slightly without causing damage. For example, the nerve can be compressed 30% without damage. In some embodiments, the nerve can be compressed 50% without damage. The housing can include a protrusion that is configured to press against the movable arm in the closed position. The protrusion can be configured to limit the amount of compression on the nerve from the movable arm.

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

[0024] In some embodiments, the transmitting step includes: using a signal generator to generate a symptom control signal and transmitting the symptom control signal using an electrode. The symptom control signal can be transmitted using one or more of a wired or wireless communication medium. 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 pulse 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. The symptom control signal can be transmitted for no less than 10 minutes and no longer than 30 minutes in a single treatment process.

[0025] Some embodiments may transmit the SUI control signal to a prescribed 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 strengthen the pelvic floor when applied via a prescribed somatic motor nerve. The SUI control signal may be configured to strengthen or repair the pelvic floor.

[0026] According to another embodiment, a system controls bladder function of a patient having symptoms (e.g., the symptoms are associated with overactive bladder (OAB) or stress urinary incontinence (SUI)). The symptoms are associated with symptom signals generated by the patient's body. The system includes a body coupled to a movable arm. A channel is defined between the body and the movable arm. The channel leads to a stimulation chamber from the outside of the body. The movable arm can be switched 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 positioned 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 stimulating the perineal nerve. In the closed position, the depth of the gap is configured to be less than about 100 microns to inhibit the perineal nerve from non-destructively entering the chamber. In the open position, the depth of the gap 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.

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

[0028] In various embodiments, the electrodes and the signal generator form an integral part of the kit. The signal generator may have a memory for storing the set of prescribed technical specifications. The set of prescribed technical specifications may include an amplitude of about 0.4 mA to 4 mA. The set of prescribed technical specifications may include: the OAB control signal is a periodic signal having a plurality of pulses. Each pulse has a pulse duration of about 200 microseconds to 400 microseconds. The set of prescribed technical specifications includes: the OAB control signal may be a periodic signal having a frequency of about 5 Hz to 20 Hz. The set of prescribed technical specifications may include a time frame for transmitting the OAB control signal. The time frame may have a duration of not less than 10 minutes and not more than 30 minutes in a single treatment process.

[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 deliver the SUI control signal after the OAB control signal. The SUI control signal may be configured to strengthen the pelvic floor when applied via the electrode and the perineal nerve.

[0030] The illustrative embodiments of the present invention are implemented as a computer program product having a computer usable medium having computer readable program code thereon. The computer readable code can be read and used by a computer system according to conventional procedures. 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," which discusses the embodiments with reference to the accompanying drawings summarized immediately below.

[0032] Figure 1A , Figure 1B , Figure 2A , Figure 2B , Figure 3A , Figure 3B , Figure 4A , Figure 4B , Figure 4C , Figure 5 , Figure 6 and Figure 7 A neuromodulation device constructed in accordance with an illustrative embodiment is schematically shown. 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 showing various nerves and related anatomical structures of an illustrative embodiment.

[0034] Figure 8B An innervation pattern of a target nerve is shown, according to an illustrative embodiment of the invention.

[0035] Fig. 9 is a neuromodulation process according to an illustrative embodiment.

[0036] FIG. 10A to FIG. 10B The device is schematically shown transitioning from a closed configuration to an open configuration in accordance with an illustrative embodiment.

[0037] FIG. 10C to FIG. 10D The device is schematically shown transitioning from a closed configuration to an open configuration in accordance with an illustrative embodiment.

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

[0039] Fig.12 Various orientations of the device body and channel / chamber orientations are schematically shown according to illustrative embodiments of the invention.

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

[0041] Fig.14 Detail of a protrusion on an arm is schematically shown according to an illustrative embodiment.

[0042] Fig.15 , Fig.16 and Fig.17 Various electrodes are schematically shown in accordance with illustrative embodiments.

[0043] Fig.18A , Fig.18B , Fig.18C , Fig.18D , Fig.18E , Fig.18F , Figure 18G , Fig.18H , Fig.19A , Fig.19B , Fig.19C , Fig. 20A , Fig. 20B and Fig. 20C Alternative embodiments of neuromodulation devices in accordance with illustrative embodiments are schematically shown.

[0044] Fig.21 A neuromodulation device is schematically shown in accordance with an illustrative embodiment.

[0045] Fig. 22 A neuromodulation device is schematically shown in accordance with an illustrative embodiment.

[0046] Fig.23A , Fig. 23B and Fig.23C A neuromodulation device is schematically shown in accordance with an illustrative embodiment.

[0047] FIG. 24A to FIG. 24B A large diameter nerve is schematically shown positioned within a chamber in accordance with an illustrative embodiment.

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

[0049] In an illustrative embodiment, a nerve is positioned into a stimulation chamber of a neuromodulatory device. The device includes a movable arm that opens to allow the nerve to enter the stimulation chamber. The arm closes to prevent or impede displacement of the nerve from the stimulation chamber without overly compressing the nerve. The movable arm is configured to hold nerves of various sizes within the chamber (e.g., the chamber accommodates nerves ranging from 0.5 mm to 4 mm). In various embodiments, the arm is biased toward a closed or substantially closed position.

[0050] Additionally, the device can be configured to hold nerves of varying sizes in the chamber and in contact with the electrodes while applying an atraumatic holding force on the nerve. The channel is similarly configured to allow the nerve to pass therethrough in response to pressure from the nerve. The pressure required to open the channel is configured to be less than a pressure that may damage the nerve. Details of an illustrative embodiment are discussed below.

[0051] Various embodiments further selectively stimulate peripheral nerves in areas with a high density of small nerves using a combination of lower power stimulation to specific neural targets without the need for destructive, time intensive and / or traumatic surgery. Prior art electrode arrays disadvantageously do not provide specific adequate stimulation to the target nerve and may cause unexpected side effects. Similarly, nerve cuffs are disadvantageously limited by predefined sizes, which are often suboptimal when connected to inappropriately sized nerves. In addition, surgical implantation methods are lengthy, invasive, and difficult to perform without damaging the nerve, particularly when the target nerve is temporarily reduced in size during implantation. Various embodiments disclosed herein advantageously deliver selective stimulation signals via electrodes in close contact with the target nerve through 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 also to allow the nerve to be secured within the chamber. Details of illustrative embodiments are discussed below.

[0053] Figures 1A to 4C A neuromodulation device 100 constructed in accordance with an illustrative embodiment is schematically shown. 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 may include a housing 48. The housing 48 may also enclose at least a portion of the movable arm 50. To this end, the housing 48 may be formed of an elastic or deformable material. The body 40 and the movable arm 50 (or the portion of the body 40 and the housing 48 surrounding the movable arm 50) may define a chamber 101 configured to receive the nerve 200 and a channel 102 leading to the chamber 101. In some embodiments, the chamber 101 may be defined by one or more arms 50. The chamber 101 includes at least one electrode 104 to stimulate the nerve 200.

[0055] The housing 48 encapsulates the package 46 of the 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 may include different types of circuits, including stimulators, sensors, communications and / or power supply circuits. In various embodiments, the package 46 may be formed of a substantially rigid material, such as titanium, stainless steel, glass, ceramics, alumina, zirconium, plastics and / or other generally acceptable airtight packaging materials. In various embodiments, the electronic package and the nerve / attachment electrode are integrated. In various embodiments, instead of the feedthrough pin extending from the airtight sealed housing welded to the electrode, the feedthrough pin forms the electrode. In such an embodiment, the electrode is unwelded (i.e., there is no welding joint connecting the electrode to the feedthrough pin). Instead, the feedthrough pin forms the electrode. When the feedthrough pin is embedded in the movable arm (e.g., silicone), the feedthrough pin serves as a reinforcing member for the deflection arm.

[0056] The package 46 forms an airtight seal around the internal electronic circuit. The electronic circuit is preferably loaded into the airtight cover 46 and sealed in an inert oxygen and water-restricted environment. After the airtight seal is formed, two advantages are provided. First, the airtight seal ensures that no additional liquid is introduced into the electronic package 46, which may cause electrical failure. Second, the airtight seal ensures that non-biocompatible materials forming the internal electronic devices will not penetrate into the body.

[0057] Preferably, the package 46 is formed of a glass or ceramic material that provides reduced interference to radio frequencies used for wireless power and wireless communications relative to other commonly used package 46 materials. The package 46 (also referred to as the hermetic cover 46) can be formed of glass wafers that are directly bonded to each other. Alternatively, the package 46 can be formed of a zirconia ceramic with a brazed feedthrough. In various embodiments, the package 46 can be sealed using a laser welded titanium surface brazed to the zirconia.

[0058] Cushioning layer 49 covers package body 46 and provides a second biocompatible layer and suitable soft surface in the human body and continuity of the portion in contact with nerve 200. As previously described, arm 50 may include an overmold housing 46 formed of a softer material (eg, 30-50 Shore A durometer).

[0059] The buffer layer 49 may be formed of a material configured to conform to its resting position in the body. Although the arms 50 and the package body 46 may be encapsulated by the housing 48, the buffer layer 49 does not cover the electrode 104. Thus, the housing 48 may have openings for the electrode 104 and / or the EMG 42. In addition, the through hole 45 may be formed through the housing. In various embodiments, the buffer layer 49 may 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 feedthrough wires, etc. The package body 46 and the buffer layer 49 may be bonded using RTV biocompatible silicone.

[0061] exist Figures 1A to 2B 1, the arm 50 is depicted as being in a closed position or a substantially closed position (collectively referred to as the closed position of the device), in which the size of the channel 102 is small enough 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 that the nerve 200 can pass through the channel 102. In some embodiments, the open position is large enough 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%. Various embodiments can be configured to receive various nerve sizes, as further discussed below. In various embodiments, the arm 50 can be biased toward the closed position (e.g., by using a biased internal member 51). The medical practitioner 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 pass through the channel 102 to enter or leave the chamber 101.

[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 package body 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 that is configured to be positioned against a concave surface of the arm 50 (e.g., Figure 3A). The dimensions of the protrusion 54 and the arm 50 may be designed to prevent the arm 50 from squeezing the nerve 200 in the 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 embodiments are included where arms 50 are enclosed by housing 48. Thus, the various embodiments are not limited to uncovered arms 50.

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

[0065] like FIG. 4A to FIG. 4B As shown, when nerve 200 is received in chamber 101, nerve 200 is substantially prevented from moving in the X or Y direction (i.e., the force of arm 51 pressing on 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, the dimensions of chamber 101 are such that nerve 200 may not be compressed at all. In such embodiments, channel 102 is narrow enough in the closed position that nerve 200 cannot escape or enter channel 102 under normal use. Figure 4A , nerve 200 is not prevented from moving in the Z direction (except by friction, which may be caused by moving nerve 200 through a compressed area). Thus, in various embodiments, when arm 50 is in a 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 move such that channel 102 has a gap that is smaller (e.g., substantially zero) than the cross-sectional dimension of nerve 200 in the closed configuration. Arm 50 may also move such that channel 102 has a gap that is greater than the cross-sectional dimension of nerve 200 in the open configuration.

[0066] It will be apparent to one skilled in the art that, in contrast to prior art nerve cuffs, the electrode 104 in various embodiments only partially surrounds the nerve 200. In other words, the nerve 200 has an outer surface circumferential section that is in partial, but not complete, 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. If the extended electrode 104A is positioned in the channel 102, the extended electrode 104A can stimulate the nerve 104. In addition, the electrode 104A can be used to stimulate the nerve 200 and provide information to the practitioner (e.g., the nerve 200 is not in the desired position to be stimulated in the chamber 101). In various embodiments, the electrode 104A can extend up 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 in the chamber 101, and the stimulation chamber 101 can induce electrical stimulation in 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 to stimulate the nerve 200.

[0068] The device 100 can be formed 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 with ultra-microscale gold metallization using well-established thin film and photolithography methods. In another example, the device 100 can be fabricated from SU-8 or other such polymers using commonly used microfabrication 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 may include circuitry for communicating with the signal generator. For example, the communication circuitry may facilitate magnetic inductive coupling or a direct conductive connection (e.g., via a wire or other hardwired electrical interface).

[0070] Chamber 101 is configured to receive nerve 200 (e.g., a human 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, nerve 200 may have an average diameter of 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, nerve 200 may have an average diameter of between about 50 μm and 4 mm, between about 50 μm and 3.5 mm, or some other range between the above exemplary sizes.

[0071] In some embodiments, chamber 101 may be generally cylindrical, wherein both 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 includes a circular cross-sectional shape, it should be understood that chamber 101 may also include a triangular, square, pentagonal, hexagonal, or polygonal cross-sectional shape having n sides while maintaining a general three-dimensional structure similar to a cylinder or tube having open ends and for receiving nerve 200. Some embodiments of chamber 101 do not have a specific cross-sectional shape, but may 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, in this example, the first and second outer surfaces 103 are located on opposite sides of device 100 and chamber 101, positioned between the first and second outer surfaces and in fluid communication with each of the opposing first and second outer surfaces 103 of device 100.

[0073] As a three-dimensional region, chamber 101 has a length, a depth, and a height. The length of chamber 101 corresponds to the z-axis, which traverses longitudinally along the nerve 200 extending through device 100. The depth of chamber 101 corresponds to the x-axis, and the height corresponds to the y-axis. In some embodiments, chamber 101 may have an average length of at least 50 μm, at least 100 μm, at least 500 μm, or at least 1000 μm. In some embodiments, chamber 101 may have an average length of about 50 μm to 11 mm (e.g., about 2 mm). In some embodiments, chamber 101 may have an average length of 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 when the chamber is in the closed position. As previously described, chamber 101 is defined in part by arm 50, which is movable. Therefore, chamber 101 has a closed configuration (also referred to as a closed position) and an open configuration (also referred to as an open position). The chamber also has intermediate configurations between the open configuration and the closed configuration, but the terminal configuration is described herein. It should be assumed that, unless the context requires otherwise, the dimensions of chamber 101 described herein refer to the closed configuration.

[0075] As described above, the depth and height of chamber 101 can be considered to correspond to the cross-sectional dimensions of the xy plane orthogonal to the z-axis of chamber 101. For example, a cylindrical chamber 101 can have a depth and height corresponding to the diameter of chamber 101. The diameter of a non-cylindrical chamber 101 can be measured by averaging the measured distances intersecting the center point of the cross section of chamber 101, where the center point is located on the z-axis extending through the middle of chamber 101. In some embodiments, chamber 101 may have an average diameter of about less than 10 mm. In some embodiments, the average diameter of 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 μm to 800 μm, or about 10 μm to 500 μm.

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

[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 is open to channel 102 indefinitely or constantly, so that the distal opening of channel 102 into chamber 101 will not be closed. In addition, channel 102 can connect the interior of chamber 101 to the outer surface 103 of device 100. Therefore, in this embodiment, chamber 101 is substantially constantly communicated with the outer surface 103 of device via channel 102. For example, chamber 101 always remains open to the channel, and channel 102 always remains open to the outer surface.

[0078] The various dimensions of channel 102 are described below. It should be assumed that the dimensions of channel 102 refer to the dimensions when channel 102 is in a closed position. As previously described, channel 102 is partially defined by arm 50, which is movable. Therefore, channel 102 has a closed configuration (also referred to as a closed position) and an open configuration (also referred to as an open position). Channel 102 also has an intermediate configuration between the open configuration and the closed configuration, but the terminal configuration is described herein. It should be assumed that, unless the context requires otherwise, the dimensions of channel 102 described herein refer to the open configuration. This is in contrast to the discussion of chamber 101, which generally refers to the dimensions of the chamber when it is in a 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 passes longitudinally along nerve 200. The length can be measured at any point along channel 102 between the distal end of the channel leading to chamber 101 and the proximal end of the channel 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, channel 102 may have an average length of at least 100 μm. In some embodiments, channel 102 may have an average length of at least 1000 μm, at least 2000 μm, or at least 4000 μm, or at least 6000 μm. In some embodiments, channel 102 may have an average length of about 100 μm to 10 mm. In some embodiments, channel 102 may have an average length of 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 distance measured between the distal opening and the proximal opening of the channel 102, wherein the distance is measured along an imaginary centerline positioned equidistantly 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, curves, or bends 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 along the imaginary centerline of the channel 102 between the distal opening and the proximal opening of the channel 102 and along each bend in the non-linear channel 102. For example, in some embodiments, the channel 102 can include an "L" shape, so that the height measurement of the channel 102 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 summing the distance from the imaginary centerline of the channel to the location where the imaginary lines of each arm intersect in the "L" of the channel 102 extending between the proximal and distal openings of the channel 102. The shape of the channel can also include other configurations, such as T-shaped, Z-shaped, and S-shaped, etc.

[0082] In some embodiments, the channel 102 may have an average height of about 100 μm to 5 mm (e.g., 4.5 mm). In some embodiments, the channel 102 may have an average height of 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] The width of channel 102 corresponds to a measurement of channel 102 positioned in an xy plane orthogonal to the z-axis, as described above. The width of channel 102 can be constant such that the width of channel 102 does not change between the proximal opening and the distal opening of channel 102. That is, in some embodiments, the width of channel 102 includes a variability of less than 10% of the average width over the entire height of channel 102. In some cases, channel 102 includes a variability of less than 5%, less than 3%, or less than 2% of the average width measured along the entire height of channel 102. In some cases, the width can be determined by measuring the shortest distance between body 40 (e.g., housing 48) and 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 about 5% to 60% less than the diameter of the target nerve 200. In some cases, the width of the channel 102 can be about 10% to 50%, about 10% to 40%, about 15% to 40%, about 20% to 35%, or about 20% to 40% less than the diameter of the target nerve 200.

[0085] In addition, similar to the above-described chamber 101, the channel 102 may 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 a longitudinal portion of the nerve 200 into the chamber 101 through the channel 102. Thus, 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 open to the interior of the chamber 101 at the distal end of the channel, and the channel can extend along the height of the channel to the third outer surface 103 at the proximal end of the channel while maintaining 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 may include various types of electrodes, including fiber or flat electrodes, thin film electrodes or needle electrodes, and other types. As an example, the electrode 104 may be implemented as a thin film electrode that has a thickness of 100 to 2000 μm on the outer surface of the nerve 200 when coupled in the chamber 101. 2 The needle electrodes in the chamber may have a needle-shaped recording and / or stimulation surface that can penetrate the surface of nerve 200 when in chamber 101. Electrodes that penetrate nerves in chamber 101 can stimulate and / or record intraneurally, which can provide greater selectivity and / or resolution when recording and / or stimulating. In addition, electrode 104 can be positioned on any of a plurality of other surfaces within chamber 101, including a top chamber surface, a bottom chamber surface, and / or a side chamber surface.

[0087] When chamber 101 has more than one electrode 104, a combination of 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. In some cases, multiple electrodes 104 can be configured as a tripolar configuration, which should provide improved neural specificity and / or selectivity while reducing extraneous biological noise.

[0088] As described above, electrode 104 can be formed at least in part by one or more conductive metals. For example, electrode 104 can 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 can have a charge injection capability of about 0.1mC / cm2 or greater. In addition, in some embodiments, electrode 104 can be a wired or wireless electrode. Wireless electrode 104 can have a wireless integrated circuit that enables communication 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 electrode comprises about 100 μm 2 Up to 1mm 2 Between or about 100μm 2 to 0.5 mm2 stimulation and / or recording surface area.

[0090] Illustrative embodiments use prescribed neuromodulation techniques to selectively activate one or more pelvic floor muscles. Among them, those pelvic floor muscles may include the cremaster muscle, the urethral bulbar muscle (Bgm), the ischiocavernosus muscle (Ism), the bulbospongiosus muscle (Bsm), the pubococcygeus muscle (Pcm), the iliococcygeus muscle (Icm), the coccygeus muscle (Cgm) or the puborectalis muscle (Prm). However, preferably, the perineal nerve is used to stimulate the pubococcygeus muscle. Alternatively, the pubococcygeus branch may also be used to stimulate it. In some embodiments, the pelvic floor muscles may be neuromodulated or stimulated simultaneously or independently with one or more other pelvic floor muscles. In some cases, the pelvic nerve may include any nerve, nerve bundle, nerve fiber bundle or nerve conduction bundle (nerve tract) that innervates the pelvic floor muscles or pelvic organs, including the pudendal nerve, the clitoral nerve or the dorsal nerve of the penis, or any branch of these 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., perineum, lower rectum) and / or the terminal branches of the levator ani nerve. In addition, some embodiments can be used in veterinary applications to stimulate animal nerves.

[0091] It should be understood that the device 100 discussed above is merely 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. Furthermore, 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 according to the illustrative embodiment is schematically shown. Note that this figure has different reference numerals for the same components than those described above, but similar components have the same or similar functions. As shown, the device includes a battery-powered or otherwise 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 may include a curved channel 1909 configured to receive a nerve. In some embodiments, at least a portion of the width of the channel 1901 may be less than the diameter of the target nerve when in a closed configuration and / or an open configuration. Thus, the target nerve can be temporarily reversibly compressed or stretched and slid through the channel until the target nerve is retained within the chamber 1907. In some embodiments, the chamber 1907 may have a diameter greater than the nerve so that the nerve is not compressed or stretched within the chamber 1907. Alternatively, the chamber 1907 may have a diameter less 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 precise and specific stimulation of the portion of the nerve that remains within chamber 1907.

[0093] Figure 6 A wireless neuromodulation device and an external system are schematically shown according to an illustrative embodiment. Figure 5 Similarly, this figure has different reference numerals for the same components than the above reference numerals, but similar components have the same or similar functions. The device has an external battery-powered or otherwise powered pulse generator and electronic controller 2001, which includes a coil to transmit power, data and / or control signals to a 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 a chamber 2009. As discussed in other embodiments, the neuromodulation device of this figure can include: a chamber 2009 that is configured to receive a nerve; and a channel 2011 (e.g., an expandable gap) through which the nerve can pass when the nerve is placed in the chamber 2009.

[0094] Figure 7 Another wireless embodiment of the system is schematically shown. Figures 5 to 7Similarly, this figure has different reference numerals for the same components than the above 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 the neuromodulation device 2115. The electromagnetic field 2103 couples with the coil 2105 of the neuromodulation device 2115. In some embodiments, the electronics and coil 2105 can be spaced apart 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 quality of the transmission between the external pulse generator and electronic controller 2101 and the neuromodulation device 2115.

[0095] In addition, the separate electronics and coil 2105 configuration can result in reduced battery requirements and applied voltage and / or amplitude. Wires 2107 can couple the electronics and coil 2105 to the neuromodulation device 2115, and more specifically to electrodes 2109 that can be located within 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 the nerve is placed in the chamber 2111.

[0096] Among other benefits, connecting an implantable electronics device having a receiver coil to a neuromodulatory device effectively decouples the receiver coil. This enables a medical practitioner to implant the receiver coil in the same position and orientation relative to hard tissue structures of the body, regardless of where the electrodes and neuromodulatory device are located. This consistency in the position and orientation of the receiver coil is expected to provide more consistent, efficient, and reliable coupling and induction in the implantable coil and electronics. This can help avoid variability in stimulation or variability in external coil position or orientation requirements.

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

[0098] To this end, the inventors were surprised to learn that acute wireless stimulation of the bulbocavernosus nerve in certain animals significantly increased maximum urethral pressure and voiding efficiency, which was proportional to the stimulation frequency. Acute stimulation was sufficient to induce a 3-fold increase in urethral pressure and urine output, indicating that activation of the perineal nerve strengthens the urethral sphincter to support continence and urination efficiency. This result confirms the ability of a miniature wireless stimulator to be used for effective pelvic floor muscle contraction and as a strategy to reverse SUI-like features in aging and multiparous rabbits.

[0099] The coccygeal plexus is anatomically and functionally different from the pelvic plexus, which includes the pudendal nerve. Therefore, sacral neuromodulation (SNM), percutaneous tibial nerve stimulation (PTNS), and pudendal nerve stimulation (PNS), all parts of the pelvic plexus, are primarily targeted at the same sacral (S2-3) segments 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 discovered that the axons innervating the pelvic floor muscles are innervated by the pelvic or coccygeal plexus and are more homogeneous anatomically and functionally and consist primarily of motor somatic efferents and proprioceptive (Ia / Ib) sensory afferents, which enter the spinal cord via anterior (S2-3) and / or more posterior (S4-5) spinal cord segments, via the perineal and / or levator ani nerves, respectively. However, proprioceptive axons ascend all the way up to lumbar (L) 7, connecting the function of the PFMs to that of the bladder and other pelvic organs. Thus, the inventors have discovered that stimulation of proprioceptive sensory afferents also inhibits activity from the bladder and have therefore discovered that such stimulation may be a useful treatment for overactive bladder syndrome. The illustrative embodiments have selected the motor branch of the perineal nerve, which controls the pubococcygeus muscles. See for details. Fig. 8A .

[0101] Figure 8B The innervation pattern of the target nerve according to an illustrative embodiment of the invention is shown. As shown, the pubococcygeus muscle is innervated by branches of the perineal and coccygeal plexuses 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, which branches from the levator ani muscles. The innervation percentages are based on the two references listed in the slide.

[0102] Various embodiments can couple and stimulate nerves to treat, among others: female sexual dysfunction, male erectile dysfunction, fecal incontinence (including but not limited to stimulation of sacral nerves), overactive bladder / urge urinary incontinence (including but not limited to stimulation of sacral or tibial nerves), pain management (including chronic pelvic pain, headaches), somatic (i.e., muscle, limb) and visceral pain (by activating mechanoreceptive or proprioceptive fibers that compete with nociceptive signals or by directly blocking signals from pain fibers), blood pressure management, sleep apnea, nausea stimulation, tremor stimulation, and / or vagus nerve, sacral root, and ventral root stimulation for various applications. Various embodiments can stimulate various nerves according to the stimulation parameters provided herein (e.g., for OAB and SUI), and stimulate for other treatments according to the same or different parameters (e.g., from those used for OAB and / or SUI).

[0103] Fig. 9 A neuromodulation process according to an illustrative embodiment is shown. It should be noted that the process is simplified from a longer process that is commonly used. Therefore, the process may have many steps that may be used by those skilled in the art. Furthermore, some of the steps may be performed in a different order than shown. Additionally or alternatively, some steps may be performed simultaneously. Therefore, those skilled in the art may modify the process as appropriate.

[0104] The process uses at least one "control signal" to neuromodulate the appropriate motor and proprioceptive nerve branches from the coccygeal and / or perineal plexus, which in this example is the perineal nerve. These control signals are referred to as:

[0105] 1) "OAB Control Signals" for managing overactive bladder syndrome; and

[0106] 2) "SUI Control Signals" for managing stress urinary incontinence.

[0107] therefore, Fig. 9 The process begins at step 1000, which sets the technical specifications of the control signals. In various embodiments, the control signals may be OAB and / or SI control signals. These technical specifications may be stored in a database, memory, or other storage medium for subsequent steps. Among other locations, such a location may be 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 technical 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 example may be the perineal nerve. These control signals are referred to as:

[0109] 1) “OAB Control Signals” – stimulation parameters for managing overactive bladder syndrome; and

[0110] 2) “SUI Control Signals” – stimulation parameters for managing stress urinary incontinence.

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

[0112] Amplitude of about 0.4 mA to 1 mA;

[0113] Each pulse has a pulse duration of 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] Stimulation pulses of approximately 10 to 20 seconds, followed by approximately 2.5 minutes off, repeated at least 3 to 4 times within a single treatment session

[0117] The duration of sending OAB control signals during a single treatment session is not less than 10 minutes and not longer than 30 minutes.

[0118] These values ​​can be appropriately scaled 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.

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

[0120] Amplitude of about 0.5 mA to 2 mA;

[0121] Each pulse has a pulse duration between about 200 microseconds and 400 microseconds (eg, 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] Stimulation pulses of approximately 10 to 20 seconds, followed by approximately 2.5 minutes off, repeated at least 3 to 4 times within a single treatment session

[0125] The duration of sending the SUI control signal during a single treatment process is not less than 30 seconds and not longer than 120 seconds.

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

[0127] Amplitude of about 0.4 mA to 1 mA;

[0128] Each pulse has a pulse duration of about 200 microseconds to 400 microseconds (when the OAB control signal is a periodic signal);

[0129] A frequency of about 5 Hz to 20 Hz (when the OAB control signal is a periodic signal); and

[0130] The duration of sending OAB control signals during a single treatment session is not less than 10 minutes and not longer than 30 minutes.

[0131] These values ​​can be appropriately scaled 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.

[0132] The SUI control signal may have a set of one or more of the following specifications for humans:

[0133] Amplitude of about 0.4 mA to 4 mA;

[0134] Each pulse has a pulse duration of about 200 microseconds to 400 microseconds (for example, when the OAB control signal is a periodic signal);

[0135] A frequency of about 60 Hz to 100 Hz (eg, when the OAB control signal is a periodic signal); and

[0136] The duration of sending the SUI control signal during a single treatment process is not less than 30 seconds and not longer than 120 seconds.

[0137] As with the technical specifications for OAB control signals, these values ​​can be scaled 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.

[0138] Typically, symptom control signals for neuromodulation of the pelvic floor may have a frequency of about 2 Hz to about 100 Hz. Nerve blocking signals may use higher frequencies, such as about 1 kHz to about 40 kHz. However, some embodiments may use lower frequencies (e.g., <10 Hz for nerve blocking).

[0139] Advantageously, both afferent and efferent control signals may be transmitted over the same nerve using the same neuromodulation device 100 .

[0140]

[0141] Experiments by the inventors have shown that efferent stimulation of the lower rectal nerve using the above-mentioned stimulation parameters can close the external and secondary rectal sphincters.

[0142] Details of various control signals that may be used are described in co-pending U.S. Patent Application No. 17 / 985,843, the entire contents of which are incorporated herein by reference.

[0143] 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 Fig. 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 pass through the channel 102 into the chamber 101 without being damaged. Therefore, transitioning to the open configuration allows the nerve to enter the chamber.

[0144] Fig. 10B and Fig. 10D Various embodiments of the device 100 in an open configuration are schematically shown. In various embodiments, the opening of the channel can have a tapered or "V" shape 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 pass through the channel 102 into the chamber 101. 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.

[0145] 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. Various embodiments can have a gap of about 0 mm to about 0.7 mm, such as 0.5 mm, in the closed configuration. Various embodiments can have a gap of about 0.75 mm, 1.75 mm, or 2.75 mm in the open configuration.

[0146] The transition to the open configuration can be achieved by the medical practitioner pulling on the movable arm 50 to cause a gap and / or sufficiently increase the size of the gap to allow the nerve to pass through (or stretch the nerve to pass through), pressing a button, or using the nerve itself to open the passage. In some other embodiments, the arm 50 can be electromechanically operated (e.g., via the push of a button). In some other embodiments, the biased arm 50 (e.g., polymer "spring loading" within its elastic range, elastomeric 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.

[0147] In some other embodiments, the force with which the nerve presses against the biasing arm 50 is sufficient to move the biasing arm 50 and allow the nerve to pass. In various embodiments, the 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 practitioner to slide the nerve into the channel 102, which is slightly opened (i.e., opened to an open configuration) to allow the nerve to pass. After the nerve passes through the channel 102, the medical practitioner prevents the channel from returning to its closed configuration and retains the unstretched nerve within the chamber 101. In the chamber 101, the medical practitioner stops stretching the nerve, so the nerve is retained in the chamber.

[0148] The process continues to step 1002, which couples the electrode to a somatic nerve (e.g., the perineal nerve), as described above. Thus, the medical practitioner can align the nerve with the channel 102 and locate the perineal nerve through the channel 102. The nerve 200 can then be secured in the chamber 101.

[0149] In some embodiments, nerve 200 can be stretched to have a thinner cross-sectional dimension to allow it to pass through channel 102. If stretched briefly, nerve 200 is released in a "free" area at the bottom of the chamber where it is allowed to recover and return to approximately its original shape and size. However, in some embodiments, the gap of channel 102 is large enough to allow the passage of unstretched nerve 200. When coupled in chamber 101, the nerve can relax or return to its normal state depending on its size.

[0150] The process then proceeds to step 1003, which converts the device to a closed configuration. As previously described, the arms 50 can be biased to be closed. Thus, the medical practitioner 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.

[0151] 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 rest in an uncompressed state in the chamber-like space, but has a gentle holding force that presses the nerve against the electrode. As the nerve moves down the channel, the spring force of the fixed arm 50 returns toward 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 seated in the chamber, after which it returns to the resting position.)

[0152] The channel can accommodate nerves 200 of a wide variety of 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 in which a channel defined by a spring-loaded arm accommodates the stretched nerve 200, rather than being "held" in place by a clamp so that the spring loading does not place undue stress on the nerve. The nerve 200 travels down the channel (e.g., a variable width channel) based on the position of the spring-loaded arm and resides in a chamber area that is also variable for the size of the nerve due to the same spring-loaded arm. While the channel is gently held closed by the spring force, the features of the chamber wall are oriented to help guide the nerve to maximize contact with the electrode.

[0153] Thus, it should be appreciated that in the closed configuration, nerve 200 may be somewhat compressed by arms 50 (eg, by nerve contacting surface 58). However, in some other embodiments, nerve 200 may not be compressed by arms 50, but may simply be trapped within chamber 101.

[0154] As described above, the nerve is preferably directly and conductively coupled to the electrode 104. Thus, preferably, no other non-negligible organic components of the patient are present 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 and still have a direct connection or coupling to the nerve.

[0155] The process then proceeds to step 1004. With the nerve safely located 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, this signal reverses and normalizes OAB symptoms. The stimulation activates the pelvic floor in a prescribed manner. However, during experiments, the inventors were surprised to discover that the signal appeared to mitigate the effects of the natural OAB signal on the pelvic floor. Specifically, the patient's body naturally sends an OAB signal (referred to as a "natural OAB signal"), which is 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, blunting or otherwise mitigating the effects of the natural OAB signal.

[0156] As described above, for a single treatment process, the method may transmit the OAB control signal to the perineal nerve for approximately 10 to 30 minutes. As described, the timing can be fine-tuned depending on the patient, severity of the disease, etc. After the OAB signal treatment is completed, the process can then continue to optional step 1006 to also treat SUI. Additionally 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 for 30 to 120 seconds during the treatment process. Additionally or alternatively, the process can send a FI signal to treat FI. Other embodiments can exchange the order of steps 1004 and 1006.

[0157] The process then proceeds to step 1007, which removes the nerve from chamber 101. Some embodiments may be permanently implanted, and thus this step may be skipped. However, advantageously, various embodiments may be easily removed. As previously described, the device transitions to an open configuration. In some embodiments, a medical practitioner may use a tool to do so. In some other embodiments, the nerve may be stretched by a medical practitioner and may be passed through channel 102. The force of the nerve may slightly open channel 102 to an open configuration. After the nerve is removed from chamber 101, channel 102 may return to its biased closed configuration.

[0158] Although various embodiments relate to movable arms that transition between an open configuration and a closed configuration, some embodiments may have non-movable arms or stationary arms. In such embodiments, channel 102 may be configured such that a nerve may pass through it atraumatically when stretched. To this end, the material of arm 50 (e.g., a cushioning layer) may be sufficiently soft to deform to allow nerve 200 to pass through.

[0159] Some or all of the process can be implemented in hardware, software, or both. For example, some or all of the process can be implemented using custom application specific integrated circuits, FPGAs, microcontrollers, or other logic, using software (e.g., firmware), and integrated with the rest of the system.

[0160] Thus, the inventors discovered that they could treat OAB and SUI through a relatively accessible somatic nerve, such as the perineal nerve. Advantageously, this nerve is very small and therefore requires much less power than many other conventional nerve stimulation systems.

[0161] Fig.11 A close-up view of the arm 50 according to an illustrative embodiment of the present invention is schematically shown. The device is shown in a closed configuration. As previously described, the closed configuration is designed to gently hold the nerve 200 in the chamber where the electrode 194 is located with two sides. The benefits of this gentle holding force are: maintaining direct contact with the nerve 200 on the wall 66 or floor 65 of the chamber 101 where the electrode 104 is located; and reducing the size of the channel 102 for smaller nerve 200 sizes. In some embodiments, the wall 66 can have a total height of 1400um from the floor to the top of the channel. The shape and size of the electrode 104 can be formed into a curved "L" to facilitate direct contact, regardless of whether the nerve 200 is at the larger end or the shorter end of the size range.

[0162] The main protrusion 62 in the spring loaded fixation arm 50 has two purposes: first, to provide a reduced width of the channel 102 to help fix the largest nerve 200 in the chamber 101 after traveling down the channel 102; second, to provide a gentle resistance to the movement of the nerve 200 to keep it in the electrode 104. The angle of this protrusion 62 is angled so that it gently urges the nerve 200 toward the electrode. In various embodiments, the protrusion 62 can have a length of 430 microns. The protrusion 62 can be used with a two-sided or angled electrode 104 (e.g., see Fig.16 ) are paired to accommodate the angle change of the spring loaded fixation arm 50 as the nerve size changes. Smaller nerves 200 are urged downward into the horizontal portion of the electrode. As this angle changes for nerve size, the largest nerves 200 are urged more toward the vertical portion. The details of these angles and distances for nerve sizes of 100 μm to 400 μm in diameter are outlined below.

[0163] In various embodiments, the spring-loaded fixed arm 50 can be primarily composed of an elastomeric material, such as silicone or plastic. Various embodiments can form at least a portion (e.g., an outer coating) of the arm 50 from a material having a Shore A hardness of 30-50. In addition, while soft neural interface materials are ideal, such as silicone, the spring-loaded arm 50 can have an overmolded or insert-molded component embedded in the silicone to provide further spring force, particularly in larger applications. Some options for the insert component are nitinol springs, stainless steel springs, other elastomeric materials or overmolded springs, and other similar materials of alternative hardness. In addition, layers of various materials with different elastomeric materials can also provide the required force. The material is preferably biocompatible for long-term implants. Some embodiments can form arms from silicone, polyurethane, embedded nitinol and / or stainless steel springs, etc.

[0164] Relief spaces 64 for nerve swelling may also be included on either side of the electrode 104. The nerve 200 is flexible and acts more like a bladder than a cable. If the nerve 200 experiences trauma 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 clip to accommodate changes in nerve size, there are one or more relief spaces 64 for the nerve to expand into to ensure that the nerve is not further damaged. The relief spaces 64 provide a relief area for any swelling or pressure buildup without interfering with the electrode-nerve contact.

[0165] Fig.12 Multiple orientations of the device body and channel / chamber orientations according to illustrative 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 to the housing 48 / body 40 of the neuromodulatory device. In addition, the channel 102 and chamber 101 can be centered or positioned to one end of the body 40 as needed to meet various anatomical requirements. Alternatively, some embodiments may separate the channel / chamber structure from the body 40 of the implant and utilize the channel / chamber structure at the end of the lead or lead extension to improve the implantation time of traditional neurostimulators.

[0166] Fig.13 Schematically depicts a device having a plurality of electrodes 104A-104D and chambers 101A-101D in accordance with an illustrative embodiment. The various chambers 101A-101D may accommodate various nerve 200 sizes. Fig.13 Also shown are different orientations of the channel 102 relative to the body 40 of the device. A two-sided electrode 104A-104D may be located in each chamber 101A-101D.

[0167] Having a series of channels 102A-102D and chambers 101A-101D (e.g., gradually getting smaller) advantageously allows a stretched nerve 200 to enter the appropriate chamber 101A-101D based on the size of the nerve. This arrangement accommodates a wider range of nerve sizes. The increased ridges provide a force to press the nerve 200 into the electrodes located in the chambers, but also prevent or inhibit larger nerves from passing through to reach the smaller chamber 101, and simultaneously prevent or inhibit relaxed nerves from leaving the chamber in which they are currently located. Additionally or alternatively, some embodiments may include a flap or latch (e.g., at the entrance of the channel 102 or at the entrance of the chamber 101) to further secure the nerve in the chamber. The flap (not shown) may be formed of silicone to hold the device in a closed configuration. The latch or securing feature may be a latch or securing feature added to the open end.

[0168] The apparatus 100 and the signal generator may be distributed separately or together as a kit.

[0169] It should be apparent that various embodiments provide many advantages. For example, electronic devices that are originally susceptible to fluid ingress and non-biocompatible are reliably separated from aqueous in vivo implant environments. In addition, the package 46 and / or the housing 48 are formed by materials selected for transmitting RF energy. The silicone overmolded housing 48 allows for the manufacture of complex shapes. Silicone can be processed at temperatures higher than the temperatures that electronic components can withstand (e.g., if they are to be injection molded). In various embodiments, the device 100 has a reliable airtight cover while having a desired (e.g., complex) external geometry and hardness to engage with tissues (e.g., nerves 200) in the body.

[0170] As a further example, the illustrative embodiments are easy to implant, i.e., the nerve slides into the chamber with minimal force. The illustrative embodiments also reduce surgical time and avoid trauma, and can be implanted in smaller spaces and with minimal changes to tissue relative to typical electrode cuffs. In addition, the illustrative embodiments can be sutureless (i.e., no complex suturing is required to secure the nerve - easy to deploy). In addition, the orientation and direction of the gentle force through the arm 50 promotes direct contact with the nerve, which results in reduced power consumption of the electrical signal directly adjacent to the nerve, maximizes stimulation, and reduces tissue ingrowth between the nerve and the electrode, thereby reducing signal degradation.

[0171] Typically, the pressure used to position the largest size nerve in 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 nerve can have a cross-sectional size (e.g., diameter) of about 0.5 mm to about 3.0 mm. However, various embodiments can accommodate larger nerves or even smaller nerves. The pressure of the holding force 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 a variety of tests. The pressure of the device on the nerve was performed on a 10X scaled model. The pressure sensor was combined with a dummy nerve filled with fluid. The nerve was inserted into the device and removed from the device, and the maximum pressure and holding pressure were recorded (the insertion of the nerve was the worst case, the clamp was not opened manually, but the nerve felt the full force of the clamp during insertion). The maximum force recorded was 15 mmHg and the maximum holding force recorded was 3.1 mmHg.

[0172] Fig.14 Schematically shows details of the protrusion 62 on the arm 50 according to an illustrative embodiment. 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 large difference in size. The calculations for the 100 μm to 400 μm example are shown below and can be scaled for alternative nerve ranges. The example provided below assumes the following:

[0173] When fully open, the width of the channel in the open configuration is 300 μm;

[0174] The portion of the raised features in the channel is slightly larger than the maximum feature size of 430 μm;

[0175] The electrodes are 450 μm in vertical and horizontal directions; and

[0176] The total height of the channel and chamber is 1.4 mm.

[0177] Electrode distance from corner (e): 0.13mm

[0178]

[0179] Figures 15 to 17 Various details of the electrode 104 according to an illustrative embodiment of the present invention are schematically shown. The electrode 104 in question can have both horizontal 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 A curved electrode is schematically shown according to an illustrative embodiment. It should be apparent that the above dimensions are exemplary only.

[0180] Fig.15 Angled electrodes are schematically shown according to illustrative dimensions. The angle between the two portions of the angled electrode 104 can be adjusted. The bent or folded electrode can provide better direct contact with the nerve than a conventional one-dimensional electrode. This allows for flexibility because the angle of pressure on the nerve varies depending on the size of the nerve so that both horizontal and vertical forces result in close contact with the conductive surface. Alternatively, in different orientations, the electrode with two sides can be constructed not only as an "L" shape, but also as a variety of internal angles to accommodate different electrode orientations. Fig.17 A folded electrode 104 is schematically shown in accordance with an illustrative embodiment. The folded electrode 104 is constructed with two sides of the electrode extending on either side of the nerve to "sandwich" the nerve between the two sides of the electrode.

[0181] FIG. 18A to FIG. 20C An alternative embodiment of a neuromodulation device 100 according to an illustrative embodiment is schematically shown. Specifically, FIG. 18A to FIG. 20C An embodiment having a plurality of jaws 50 (e.g., formed of silicone or including a silicone overmold as previously described) is shown. The body 40 is omitted in some of these 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 having the channel 102 opening oriented substantially perpendicular to the body 40, FIG. 18A to FIG. 20C The passage 102 opening is shown oriented substantially parallel to the longitudinal axis of the body 40. However, in other embodiments, the passage 102 may be oriented in any direction (e.g., diagonally to the body 48). It should also be understood that the orientation relative to the body may depend on the orientation and size of the body.

[0182] 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, the body 40 and the housing 48 are not shown in FIG. FIG. 18A to FIG. 20C 4, but it should be understood that various embodiments of jaw 50 may be coupled to housing 48 and / or enclosure 46.

[0183] Advantageously, a single device 100 is configured to couple with and stimulate nerves 200 of various sizes (eg, 0.5 mm to about 4 mm).

[0184] Although the subject 48 Fig.18A104. The body 48 is shown as being smaller than the jaws 50, but it should be understood that the drawings are not necessarily drawn to scale. In some embodiments, the body 48 can be larger or smaller than the jaws 50. Additionally, in various embodiments, the body 48 can form a portion of the chamber 101 having the electrodes 104. However, in some 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.

[0185] 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.

[0186] For the sake of discussion, 18A to 18C The nerve shown in is a small nerve with a diameter of about 1 mm. The jaws 50 together define a V-shaped funnel 68 on the exterior of the device 100, and the funnel 68 is configured to help the surgeon position the nerve 200 at the proximal end 72 of the channel 102. When the nerve 200 is positioned at the proximal end 72 of the channel 102, the nerve 200 preferably has a larger cross-sectional dimension than the channel 102. For example, the channel 102 may have a cross-sectional dimension of about 0.45 mm to about 0.75 mm. However, in some embodiments, the channel 102 may be completely closed (e.g., with a dimension of about 0 mm). Advantageously, the reduced channel size 76 prevents accidental displacement of the nerve 200. In addition, to this end, the channel 102 may have a non-linear or tortuous shape to help prevent accidental displacement of the nerve 200. However, some embodiments may include a linear channel 102.

[0187] 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 that might otherwise occur due to a greater 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 a channel size 76 of 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 and thereby expand the channel size 76. In some embodiments, the hinge 78 is formed of a deformable material (e.g., silicone) that allows the jaws 50 to open outward. Additionally or alternatively, the channel 102 may include a deformable and / or elastic wall or coating that allows the channel size 76 to be expanded.

[0188] like Fig.18CAs 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 reduced channel size 76 and the non-linear channel 102 shape, the small nerve 200 is firmly 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 can be biased to return to the closed position, and / or the deformable material can be elastic and return to its original size.

[0189] Fig.18D A perspective view of the device 100 is schematically shown (details of the chamber 101, such as the electrode 104, are omitted). The channel 112 has a specific travel path 113 (also referred to as a 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.

[0190] In addition to the central axis 113, the device 100 has a longitudinal axis 112 that is orthogonal to the central axis 113 at any given point. During a nerve implantation procedure, the nerve 200 is generally parallel to the longitudinal axis 112 as it travels along the central axis 113. Two different longitudinal axes 112A and 112B are shown for two different points along the central axis.

[0191] Fig.18E Schematically shows Fig.18D 1. As shown, channel 102 is axial such that longitudinal axis 112A is uninterrupted. This allows nerve 200 to be passed through channel 102 with minimal manipulation by the surgeon. In some embodiments, nerve 200 may be stretched to pass through channel 102, and / or the channel walls formed by jaws 50 may be deformable. Figure 18G A nerve is schematically shown passing through channel 102 at a cross section of axis 112A.

[0192] 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. Therefore, the channel can be said to be continuously axial, that is, the longitudinal axis 112 at any given point along the central axis 113 is uninterrupted.

[0193] Fig.18H Schematically shows the FIG. 18E to FIG. 18GIn particular, longitudinal axis 112C is interrupted (e.g., by teeth 151). In order to allow nerve 200 to pass through Fig.18H To narrow channel 102, the surgeon must very carefully manipulate nerve 200 (e.g., to conform to the shape of axis 112C), force the nerve through by applying traumatic pressure, or actively open jaws 50 (e.g., with a separate tool). Fig.18H The longitudinal axis 112C does not have an axial orientation when at rest (as shown), but can become axial when the jaws 50 are opened. However, the illustrative embodiment advantageously has axial longitudinal axes 112A, 112B when at rest so that the nerve can easily slide into the chamber 101.

[0194] Thus, some embodiments have a non-linear channel 102 (ie, along the central axis 113) that is continuously axial, such as FIG. 18D to FIG. 18F Advantageously, the nerve can be passed through the channel 102 with minimal manipulation, atraumatically, and without the need for a separate tool to open the arm 50 .

[0195] FIG. 19A to FIG. 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. The figure shows a side view of device 100.

[0196] For the sake of discussion, FIG. 19A to FIG. 19C The nerve 200 shown in is a medium sized nerve having a diameter of approximately 2 mm. Similar to the previously described process, the V-shaped funnel helps to position the nerve 200 relative to the proximal end 72 of the channel 102. For the sake of discussion, the nerve 200 can be stretched to reduce the nerve diameter to approximately 1.5 mm. As previously described, 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 width of the channel 102. The jaws 50 can expand open to increase the channel dimension 76 and allow the nerve 200 to pass through the channel. To this end, the illustrative embodiments may include a delivery device having a cam feature that presses the jaws 50 to open via deformation and / or articulation. Although Fig.18B The hinge is schematically shown split open, but various embodiments do not have a hinge opening (which could otherwise capture a portion of the larger deformed nerve).

[0197] like Fig.19CAs shown, the nerve 200 stays in the chamber 101 and the jaws 50 can be reclosed. For example, the nerve 200 relaxes and returns to its 2 mm diameter. In addition, the silicone of the jaws 50 can relax and the channel dimension 76 returns to about 0.5 mm, thereby preventing the nerve from exiting the channel 102. In some embodiments, the jaws 50 are biased to a rest position (e.g., in the rest position, the channel 102 has a dimension 76 of about 0.5 mm or is biased to a fully closed position). Additionally or alternatively, the delivery device can close the jaws 50. The silicone deforms and the small Z-shaped channel 102 firmly connects the medium-sized nerve in the chamber 101.

[0198] FIG. 20A to FIG. 20C The process of positioning a large nerve 200 (e.g., about 2.5 mm to about 3.5 mm in diameter) within chamber 101 for stimulation is schematically illustrated. These figures show a side view of device 100. Fig. 20A As shown, the device 100 is considered to be at rest or in a rest position. In the rest position, the device is in a stable state, i.e., no force is applied to the device to open the jaws 50 (e.g., through the nerve or through a tool). Therefore, in various embodiments, the rest position is a "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 various embodiments, the device has an open channel 102 when at rest. In addition, when the device is at rest (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). Such closure can be applied along the channel 102 without limiting the ability to use a sliding lock nerve positioning method.

[0199] For the sake of discussion, FIG. 20A to FIG. 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 positioned at the proximal end 72 of the channel. The device 100 can have a chamber size 83A (e.g., such as a maximum chamber size or a minimum chamber size) in which there is no nerve 200.

[0200] like Fig. 20BAs shown, the nerve 200 can travel 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, because otherwise a greater reduction in cross-sectional size may 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 size 76 of the channel 102 to allow the large nerve 200 to pass through the channel 102. Therefore, various embodiments have a chamber 101 of adjustable size and / or shape. Similarly, the chamber size 83B can be adjusted by movement of one or more arms 50.

[0201] like Fig. 20C As shown, when the nerve 200 passes through the distal end 74 of the channel 102 and enters the chamber 101, the jaws 50 may close again. However, due to the large size of the nerve 200, the jaws 50 may or may not be able to fully close to return the channel 102 to its original size 77. In a similar manner, the arms 50 may or may not be able to fully close to return the chamber 101 to its original size 83A. When the nerve 200 is positioned in the chamber 101, the chamber 101 may 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 may include relief spaces 64 (also referred to as deformation regions 64) in which the shape of the nerve 200 may deform and expand when compressed (e.g., so that the cross-sectional area of ​​the nerve is not reduced as much as it would be without the deformation regions 64). In various embodiments, the nerve 200 may deform and / or expand in one or more relief spaces 64 in order to reduce the pressure applied to the nerve. Taking into account the nerve free space 64, the device can be configured so that less than 4 kPa of pressure is applied to the nerve. In addition, to help reduce the pressure applied to the nerve 200, the contact surface 58 can be configured to deform, thereby giving the nerve 200 additional space to expand within the chamber 101. In addition, in some embodiments, and as Fig. 20C As shown, the channel 102 dimension 76 may expand in the resting configuration due to interference with the greater nerve 200 .

[0202] Due to the reduced channel size 76 and the shape of the non-linear channel 102, the small nerve 200 is securely coupled within the chamber 101. Although not drawn to scale, the jaw 50 may include a nerve contacting surface 58 configured to press and / or hold the nerve 200 against the electrode 104.

[0203] It should be appreciated that various embodiments advantageously allow nerve 200 to expand / deform within chamber 101, as opposed to compensatory expansion / deformation that might otherwise 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 jaws with deformable nerve contact portions and designated relief spaces 64 within the device to allow deformation near / localized at areas of compression on the nerve. As is known in the art, nerves are comprised of bundles of axons. By allowing localized deformation of the nerve, the positions of individual axons and / or bundles can be rearranged without necessarily damaging any individual axon (as might occur if the nerve were severely compressed or stretched).

[0204] Fig.21 and Fig. 22 A neuromodulation device 100 is schematically shown in accordance with an illustrative 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 a chamber 101, which is defined by the movable arm 50.

[0205] The movable arm 50 is shown as being biased toward a closed position. Although referred to as a "closed position," some embodiments may have a gap 76. Thus, the movable arm 50 does not have to completely close the gap 76 in the closed position. The closed position 76 is used to refer to the position of the channel 102 when the channel is narrow to hold a nerve. As the nerve passes through the channel 102, the gap 76 increases (e.g., because the arm 50 moves and / or deforms), and the movable arm 50 transitions toward an open position. To help facilitate opening of the channel, 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 have to be completely closed to be biased toward the closed position. In a similar manner, the gap 76 does not have to be completely open to transition toward the open position.

[0206] As previously described (e.g., see FIG. 18A to FIG. 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 slide-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 such that the longitudinal axis of the channel 112 changes direction along its length (e.g., Fig.18HHowever, embodiments having axial passage 112 advantageously may utilize a sliding locking method, for example, by axially stretching nerve 200 and sliding it through continuous axial passage 102. This method advantageously does not require the use of external tools or other forces (other than the pressure of the nerve against jaws 50) to help open jaws 50 to allow the nerve to traverse passage 102.

[0207] Fig. 22 Four different views of alternatives of movable arm 50 are shown in accordance with an illustrative embodiment. Fig. 22 A curved feature 81 is shown that is configured to move for a larger nerve 200 as it passes through the passage 102 and / or when the larger nerve 200 is positioned in 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 passage 102 and / or chamber 101.

[0208] 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 an unjoined (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 an unjoined 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 may 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 positioned 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 positioned in the chamber 101.

[0209] As shown, various embodiments combine a neural connection portion (i.e., chamber 101) and an implantable pulse generator (e.g., within a package 46), thereby advantageously providing a smaller device 100 and a simpler implantation procedure. In addition, various embodiments do not require external leads between the neural connection portion and the IPG. Advantageously, a single unbonded feedthrough conductor 81 can extend from the hermetically sealed housing 46 into the chamber 100 to form an electrode 104. This is in contrast to a device in which the feedthrough conductor 81 is welded to the electrode 104. Illustrative embodiments may use the feedthrough conductor directly as the electrode 104, thereby providing an unbonded or continuous electrode.

[0210] Prior art devices implant the IPG by exposing the nerve to place the cuff; then using a custom tool to tunnel the lead to the location of the IPG, where a pit is formed under the skin to place the IPG; then connecting the IPG to the lead and placing the IPG in the pit. In contrast, the illustrative embodiments provide a simpler procedure because the sizing of the nerve is automatic (within an acceptable range of approximately + / - 50% to 75%, which ranges from 0.5-3.5 mm for a 2 mm nerve). Advantageously, there is no tunneling and there is no need to have a separate surgical site for the IPG.

[0211] In addition, the entire lead body is not required, as well as the connector block, proximal connector and other similar components. 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, for example, from a Pt-Ir material. An additional benefit 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 to atraumatically connect the nerve 200.

[0212] Thus, the illustrative embodiments provide a neuromodulation device in which feedthrough conductor 81 serves as both electrode 104 and structural component that are combined to achieve appropriate flexure characteristics of arm 50. The material properties are selected so that nerve 200 is in intimate contact with electrode 104, but not in traumatic contact.

[0213] The movable and / or flexible arm 50 can be adjusted during insertion of the nerve into the channel 102 and when the nerve is positioned 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).

[0214] The illustrative embodiment is configured to hold a nerve 200 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 easily damaged by high pressure. Therefore, the illustrative embodiment forms arm 50 from a material that offsets the arm to reduce the pressure on nerve 200 when nerve 200 passes through channel 102 and when nerve 200 stays in chamber 101. In particular, arm 50 is configured to apply less than 6.7 kPa on nerve 200 to prevent structural damage to the nerve. For example, channel 102 preferably has an opening pressure of less than 6.7 kPa. In various embodiments, device 100 is configured so that less than 10 kPa or less than about 1.5 psi pressure is applied to the nerve. Of course, some embodiments can provide higher pressures than disclosed herein. Depending on the amount of time that nerve 200 is in channel 102, the pressure can be reduced. For example, if it takes 2 minutes or more to pass the nerve through channel 102, device 100 should be configured so that less than 6.7 kPa pressure is applied to the nerve. In a similar manner, the nerve 200 is located in the chamber for a long time, and therefore, the device can be configured so that less than 4 kPa pressure is applied 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.

[0215] In addition, the illustrative embodiment is configured to retain nerves having a size of 0.5 mm to 4 mm in chamber 101 at a pressure of less than 4 kPa (or 30 mmHg) to reduce undesirable long-term effects, such as blockade of nerve function and / or edema. Thus, chamber 101 preferably has a holding pressure of less than 4 kPa for nerves 200 having a diameter of 1 mm to 3 mm (nerve diameter is a generally accepted size measurement of a nerve when the nerve is at rest and undeformed).

[0216] Bench testing of device 100 showed that the maximum insertion force for a large nerve (e.g., 4 mm diameter) was less than 2 kPa (15 mmHg), and after the model nerve was seated in the chamber, the compression averaged 0.147 kPa (1.1 mmHg), indicating that the flexible channel / chamber approach is a viable approach.

[0217] Furthermore, some electrodes implanted in nerves in clinical studies chronically compress them (by about 40%). These are called "flat" electrodes (mostly thin electrodes), and it has been reported that estimated intrafascicular pressures of less than 30 mmHg can reshape the nerve without significantly altering nerve physiology or histology. Flattening a nerve by more than 60% applies a pressure of 60 mmHg and can cause nerve damage. As mentioned in the previous paragraph, early bench testing of nerve clamps showed that chronic compression values ​​far below the 60 mmHg shown with "flat" electrodes could be achieved.

[0218] The illustrative embodiments provide a neuromodulation device that is configured to atraumatically couple to various nerve sizes from 0.5 mm to 4 mm. As described herein, the atraumatic coupling provides a sustained pressure of less than 4 kPa on the nerve while the nerve is in the chamber (e.g., in the chamber for hours, days, etc.). In addition, the atraumatic coupling provides less than 6.7 kPa when passing through the channel 102 (e.g., passing through the channel in a short period of time of less than 1 minute).

[0219] The device 100 is configured to accommodate a variety of nerve sizes (eg, from 1 mm to 3 mm). The same approach can be scaled to multiple nerve size ranges.

[0220] To accommodate a variety of nerve sizes, the device is flexible enough to allow the largest nerves to pass through the channel portion and stay in the chamber, but not too large to allow the smallest nerves to easily slide out while maintaining contact with the electrodes. To this end, various embodiments use Nusil (Nusil products with Class VI biocompatibility approval) silicone, a biomaterial widely used in long-term active implantable devices. The material bends to accommodate the largest nerves passing through the channel 102, and also reshapes into the additional space when the nerve is in the chamber, providing this additional space to prevent pressure accumulation inside the nerve. Rather than a large round nerve being overly compressed in the chamber, the nerve shape changes to fill the open space provided. Nerve 200 can withstand moderate reshaping of the cross-sectional shape without causing damage (e.g., a 30% reduction in the maximum cross-sectional area).

[0221] FIG. 23A to FIG. 23C A neuromodulation device is schematically shown in accordance with an illustrative embodiment. Fig.23A A 1 mm nerve is shown pressed against arm 50 and protrusion 54. In some embodiments, arm 50 may be movable and deflect in response to pressure from the nerve. Additionally or alternatively, arm 50 and / or protrusion 54 are formed of a deformable material (e.g., a cushioning layer) that deforms to expand the channel gap. In some other embodiments, arm 50 may be static. Fig. 23B The nerve is shown deforming to pass through the continuous axial channel 102. Finally, Fig.23C Nerve 200 is shown positioned against electrode 104. Unlike static arm 50, the illustrative embodiment having movable arm 50 can provide a contact pressure against nerve 200 that pushes nerve 200 into contact with electrode 104.

[0222] Fig.23CThe nerve shown in is a relatively small nerve (e.g., 1 mm diameter). Larger nerves (e.g., 3 mm and above) deform to match the available space in chamber 101 without applying traumatic pressure along the nerve after remodeling. Figures 23D and 23E schematically illustrate that a large nerve changes its cross-sectional shape but maintains its cross-sectional area.

[0223] Additionally, 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. Tests performed by the inventors using a device with one movable arm 50 for large nerves (e.g., 3 mm or larger) found that pressures were less than 5 mmHg after placement in the chamber.

[0224] It should be apparent that the illustrative embodiments provide the advantage of a single device that can be coupled to and reliably stimulate nerves of various sizes. In addition, the device can reliably hold nerves of various sizes (e.g., from a small 0.5 mm diameter to a large 4 mm diameter) without causing excessive compression / trauma to the nerve 200. In practice, chamber 101 (e.g., a portion of movable arm 50) adjusts to help hold the nerve.

[0225] Various embodiments use a combination of epoxy and medium durometer silicone (e.g., 60-90 Shore A), with or without additional structural components. For example, epoxy can be used to support the feedthrough conductors to minimize flexural strain points. The feedthrough conductors (e.g., Pt-Ir, gold, nitinol, or similar materials) are bent and bonded into the head structure to provide additional structural support and retention. The feedthrough or attached electrode is then embedded into a low to medium durometer silicone portion (typically 30-50 Shore A) that is flexible to achieve the positioning and resistance required to hold the nerve in place without trauma to the nerve. This structure is different from a typical nerve because the cuff requires both the nerve and the cuff to deform in extreme cases to allow the nerve to "slide" through the channel and into the chamber. By taking advantage of the nerve's natural ability to flex and the slight movement of the silicone or wire arms of the device, acute pressure on the nerve is minimized, even in the case of the largest 50-75% of larger nerves. Furthermore, by utilizing the ability of the largest nerve to adjust and redistribute its structure to minimize internal nerve pressure at the lowest resting or final force, there is sufficient space in the chamber to allow the nerve to relax and achieve a resting pressure well below the 60% compression known to cause injury.

[0226] 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 feedthrough flexure structure as the electrode provides ample opportunity to maintain close connection between nerve and electrode, thereby minimizing the impact on signal strength.

[0227] Therefore, in various embodiments, the channel 102 and / or chamber 101 can be formed of a material configured to deform in response to atraumatic pressure (e.g., less than 6.7 kPa) from a nerve. In addition, the channel 102 and / or chamber 101 is configured to change its size due to one or more movable arms 50.

[0228] Among other advantages, the continuous axial channel 102 of the illustrative embodiment provides for easy installation of the nerve into the chamber 101 and easy 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 does not easily 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 the arm 50 and / or deform the arm 50 to allow the nerve to pass.

[0229] 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 additionally provide a non-invasive force that non-invasively biases 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 larger), electrode 104 contacts at least 60% of the circumference of the nerve when nerve 200 is in chamber 101. Thus, device 100 advantageously atraumatically accommodates nerves of various different sizes. Furthermore, one or more arms 50 assist in continuous contact and electrical connection with electrode 104 by providing a limiting force to compress the nerve. Furthermore, the illustrative embodiments couple the device to the nerve without the use of sutures and without the need for specialized tools, which allows for easy removal of the device.

[0230] Although various embodiments describe devices for coupling to and treating nerves having a diameter of about 0.5 mm to about 4 mm, it should be understood that such devices and methods are scalable to accommodate nerves of various different sizes. For example, one skilled in the art can use the disclosure herein to configure a device to couple to larger nerves having a diameter of about 5 mm to about 8 mm. As another example, the device can be configured to couple to a nerve 200 having a diameter of about 0.2 mm to about 2 mm. These devices can be configured to couple to a variety of nerve sizes without damaging the nerve (e.g., by applying a pressure of less than 4 kPa to the nerve).

[0231] Although various inventive embodiments have been described and illustrated herein, a person of ordinary skill in the art will readily conceive of various other devices and / or structures for performing functions and / or obtaining results and / or one or more advantages described herein, 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 intended to be exemplary, and that actual parameters, dimensions, materials, and / or configurations will depend on one or more specific applications for which the present invention is taught. Those skilled in the art will recognize or be able to determine many equivalents of the specific inventive embodiments described herein using no more than routine experiments. Therefore, it should be understood that the foregoing embodiments are presented only as examples, and within the scope of the appended claims and their equivalents, the inventive embodiments may be implemented in a manner different from that specifically described and claimed. The inventive embodiments of the present disclosure relate to each individual feature, system, article, material, kit, and / or method described herein. In addition, if such features, systems, articles, materials, kits, and / or methods are not mutually contradictory, any combination of two or more such features, systems, articles, materials, kits, and / or methods is included within the scope of the invention disclosed herein.

[0232] Various inventive concepts may be embodied as one or more methods, examples of which have been provided. The actions performed as part of a method may be ordered in any suitable manner. Thus, embodiments may be constructed in which the actions are performed in an order different from the order shown, which may include performing some actions simultaneously, even though shown as sequential actions in an illustrative embodiment.

[0233] Although the subject matter contained herein has been described in detail for purposes of illustration, it should be understood that such detail is provided for that purpose only and that the present disclosure is not limited to the disclosed embodiments, but, on the contrary, 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 present disclosure contemplates that, to the extent possible, one or more features of any embodiment may be combined with one or more features of any other embodiment.

[0234] Other examples are 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 of these. Features that implement functions can also be physically located in various locations, including the features being distributed so that parts of the functions are implemented at different physical locations.

[0235] Although the subject matter contained herein has been described in detail for the purpose of illustration, it should be understood that such detail is for that purpose only and that the present disclosure is not limited to the disclosed embodiments, but on the contrary 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 present disclosure contemplates that, to the extent possible, one or more features of any embodiment may be combined with one or more features of any other embodiment.

[0236] Other examples are 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 of these. Features that implement functions can also be physically located in various locations, including the features being distributed so that parts of the functions are implemented at different physical locations.

Claims

1. A neuromodulator, comprising: a body, the body comprising a buffer layer and a hermetically sealed housing, the hermetically sealed housing accommodating the electronic device therein, the buffer layer at least partially encapsulating the hermetically sealed housing; a movable arm coupled to the body, the movable arm being configured to transition between an open configuration and a closed configuration, the movable arm being biased toward the closed configuration; a neural stimulation chamber defined at least in part by the movable arm, the neural stimulation chamber being configured to retain a nerve therein, the size and shape of the chamber being adjustable by movement of the arm in response to contact with the nerve; an open channel through which the nerve travels, the channel being defined at least in part by the movable arm, the size and shape of the channel being adjustable by movement of the arm in response to contact with the nerve, wherein when the movable arm of the device is in the closed configuration, the channel is continuous axial along a longitudinal axis of the channel; and Electrodes within the chamber.

2. The neuromodulatory device 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.

3. The neuromodulator according to claim 1, wherein: The movable arm is configured to atraumatically retain a nerve having a resting maximum cross-sectional dimension of 0.5 mm to 4 mm in the chamber when the movable arm is biased toward the closed configuration.

4. The neuromodulation device according to claim 1, wherein: The chamber includes one or more nerve relief spaces defined by the movable arm.

5. The neuromodulator according to claim 1, wherein: The movable arm includes one or more flexure points.

6. The neuromodulation device according to claim 1, wherein: The distal end of the electrode is embedded in the movable arm.

7. The neuromodulator according to claim 1, wherein: Continuous feed-through electrical wires extending through the hermetically sealed housing form the electrodes.

8. The neuromodulator according to claim 7, wherein: The channel is non-linear.

9. The neuromodulation device according to claim 1, wherein: The chamber is configured such that the electrode is curved and the electrode is sized to contact at least 20% of the circumference of a nerve having a maximum cross-sectional dimension of 0.5 mm to 4 mm.

10. The neuromodulation device according to claim 1, wherein: The channel is non-linear and continuous axially.

11. A method for stimulating nerves, the method comprising: A neuromodulatory device is provided, the neuromodulatory device having: a body, the body comprising a buffer layer and a hermetically sealed housing, the hermetically sealed housing accommodating the electronic device therein, the buffer layer at least partially encapsulating the hermetically sealed housing; a movable arm coupled to the body, the movable arm being configured to transition between an open configuration and a closed configuration, the movable arm being biased toward the closed configuration; a neural stimulation chamber defined at least in part by the movable arm, the neural stimulation chamber being configured to retain a nerve therein, the size and shape of the chamber being adjustable by movement of the arm; a channel through which the nerve travels, the channel being defined at least in part by the movable arm, the size and shape of the channel being adjustable by movement of the arm, wherein the channel is continuously axial along a longitudinal axis of the channel; and electrodes within the chamber; reducing a maximum cross-sectional dimension of the nerve to define a stretched nerve having a reduced cross-sectional dimension; moving the stretched nerve along the central axis through the passage; The nerve is positioned in the chamber and the cross-sectional size of the stretched nerve is increased.

12. The method according to claim 11, further comprising: transmitting a control signal to the prescribed nerve via the electrode; The control signal is configured to activate the pelvic floor in a prescribed manner to reduce the effects of the symptom signal on the spinal cord.

13. The method according to claim 11, wherein: The predetermined nerve is positioned within the chamber so that the predetermined nerve is in contact with the electrode.

14. The method according to claim 11, wherein: Positioning the movable arm in the closed position compresses the prescribed somatic nerve in the chamber such that a cross-sectional shape of the nerve is altered without damaging the nerve.

15. The method according to claim 11, wherein: The housing includes a protrusion configured to press against the movable arm in the closed position, the protrusion configured to limit an amount of compression of the nerve by the movable arm.

16. The method according to claim 11, wherein: A continuous feed-through conductor extending through the hermetically sealed housing forms the electrode.

17. The method according to claim 11, wherein: The electrode contacts greater than 50% of the circumference of the nerve.

18. The method according to claim 11, wherein: The movable arm is biased toward the closed position.

19. The method according to claim 11, wherein: The prescribed somatic motor nerve comprises a perineal nerve, further wherein the perineal nerve or a pelvic floor nerve is part of the coccygeal plexus and / or the perineal plexus.

20. The method according to claim 11, wherein: The transmitting step includes: using a signal generator to generate the symptom control signal and transmitting the symptom control signal using the electrode, the symptom control signal being transmitted using one or more of a wired or wireless communication medium.

21. The method according to claim 11, wherein: The amplitude of the symptom control signal is approximately 0.4 mA to 4 mA.

22. The method according to claim 11, 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.

23. The method according to claim 11, wherein: The symptom control signal is a periodic signal having a frequency of about 5 Hz to 20 Hz.

24. The method according to claim 11, wherein: The transmitting step includes transmitting the symptom control signal for no less than 10 minutes and no longer than 30 minutes during a single treatment process.

25. The method according to claim 11, further comprising: A SUI control signal is transmitted to the prescribed somatic motor nerve via the electrode, the SUI control signal having a frequency different from a frequency of the OAB control signal.

26. The method according to claim 25, wherein: The SUI control signal is transmitted after the OAB control signal.

27. The method according to any one or more of claims 26, wherein: The SUI control signal is configured to strengthen the pelvic floor when applied via the prescribed somatic motor nerves.

28. The method according to claim 11, wherein: The SUI control signals are configured to strengthen or repair the pelvic floor.

29. A system for controlling bladder function in a patient having symptoms (e.g., symptoms associated with overactive bladder (OAB) or stress urinary incontinence (SUI)) associated with symptom signals generated by the patient's body, the system comprising: a body coupled to the movable arm, wherein a passage is defined between the body and the movable arm, the passage leading from an exterior of the body to the stimulation chamber; the movable arm being convertible between a closed position and an open position such that the channel has a gap, the depth of the gap being greater in the open position than in the closed position; an electrode positioned in the chamber, the electrode being configured to couple with the perineal nerve, the electrode having a receiving interface configured to receive an OAB control signal for stimulating the perineal nerve; wherein, in the closed position, the depth of the gap is configured to be less than about 100 microns to inhibit non-destructive entry of the perineal nerve into the chamber, Wherein, in the open position, the depth of the gap is configured to be large enough (eg, approximately 0.5 mm to 2.5 mm) to allow the nerve (eg, the perineal nerve) to pass through.

30. The system of claim 29, wherein: In the closed position, the depth of the gap is zero.

31. The system of claim 29, further comprising: a signal generator having a transmit interface configured to communicate with a receive interface of the electrode, The signal generator is configured to transmit an OAB control signal to the electrode via the transmitting interface and the receiving interface, The OAB control signal has a prescribed set of specifications to activate the pelvic floor in a prescribed manner to mitigate the effects of the natural OAB signal on the pelvic floor.

32. The system of claim 29, wherein: The electrodes and the signal generator form part of a kit.

33. The system of claim 29, wherein: The signal generator has a memory for storing the set of specified technical specifications.

34. The system of claim 29, wherein: The set of prescribed specifications includes an amplitude of approximately 0.4 mA to 4 mA.

35. The system of claim 29, wherein: The set of prescribed technical specifications includes: the OAB control signal is a periodic signal having a plurality of pulses, each pulse having a pulse duration of approximately 200 microseconds to 400 microseconds.

36. The system of claim 29, wherein: The set of prescribed technical specifications includes: the OAB control signal is a periodic signal with a frequency of approximately 5 Hz to 20 Hz.

37. The system of claim 29, wherein: The set of prescribed technical specifications includes a time frame for transmitting the OAB control signal, the time frame having a duration of no less than 10 minutes and no more than 30 minutes during a single treatment session.

38. The system of claim 29, further wherein: The signal generator is configured to transmit a SUI control signal to the perineal nerve, the SUI control signal having a frequency different from a frequency of the OAB control signal.

39. The system of claim 47, wherein: The signal generator is configured to transmit the SUI control signal after the OAB control signal.

40. The system of any one or more of claims 39, wherein: The SUI control signal is configured to strengthen the pelvic floor when applied via the electrode and the perineal nerve.

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