Systems and methods for nerve stimulation

Abstract

The nerve modulation device includes a movable arm coupled to the body. The movable arm is configured to transition between an open configuration and a closed configuration. The movable arm is biased toward the closed configuration. 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 moves. The channel is at least partially defined by the movable arm. The size and shape of the chamber and the channel are adjustable by movement of the arm in response to contact with the nerve. The channel can be continuously axial along the longitudinal axis of the channel when the movable arm is in the closed configuration. The chamber has an electrode.

Description

Technical Field

[0001] Priority This patent application claims the benefit of priority of U.S. Provisional Patent Application No. 63 / 391,574, filed Jul. 22, 2022, and U.S. Provisional Patent Application No. 63 / 391,584, filed Jul. 22, 2022, the disclosures of which are hereby incorporated by reference in their entireties.

[0002] Field of the Invention Exemplary embodiments of the present invention generally relate to pelvic organ function, and more particularly, various embodiments of the present invention relate to selective neuromodulation for regulating bladder and pelvic floor function.

[0003] Background Art Overactive bladder ("OAB") affects millions of people in the United States and around the world and can cause debilitating urgency and frequent urination, with or without incontinence. Paradoxically to many in the art, OAB is associated with nocturia, without urinary tract infection or other obvious pathologic conditions. The pathophysiology and etiology of idiopathic OAB remain unknown, but it appears to be associated with detrusor muscle dysfunction or detrusor overactivity. Current pharmacological treatments include oral antimuscarinics or oral β3-adrenergic receptor agonists. Such treatments have significant drawbacks as their efficacy and tolerability are limited and they cause significant side effects including dry mouth, dry eyes, constipation, tachycardia, and potential long-term cognitive effects. As a result, studies have shown that the majority of OAB patients discontinue taking these medications within 6 to 12 months of treatment.

[0004] Another urinary problem known as "stress urinary incontinence" ("SUI") occurs when urine leaks due to sudden pressure on the bladder and urethra, causing the sphincter to open briefly. In mild SUI, the pressure can be due to moderate exercise, sneezing, laughing, or sudden strenuous activities such as coughing. However, if SUI is more severe, urine may leak during less strenuous activities such as standing, walking, or bending forward. Such urine "accidents" can range from a few drops of urine to an amount sufficient to soak through clothing.

[0005] Those skilled in the art typically treat both OAB and SUI with different treatment regimens.

[0006] SUMMARY OF THE INVENTION According to one embodiment, a neuromodulation device includes a body having a sealed housing that houses an electronic device. The body has a buffer layer that at least partially encapsulates the sealed housing. A movable arm is coupled to the body. The movable arm is configured to transition between an open configuration and a closed configuration. The movable arm is biased toward the closed configuration. A nerve stimulation chamber is at least partially defined by the movable arm. The nerve stimulation chamber is configured to hold a nerve therein. The size and shape of the chamber are adjustable by movement of the arm in response to contact with the nerve. The device has an open channel through which the nerve moves. The channel is at least partially defined by the movable arm. The size and shape of the channel are adjustable by movement of the arm in response to contact with the nerve. The channel can be continuously axial along the longitudinal axis of the channel when the movable arm is in the closed configuration. The chamber has an electrode.

[0007] Some embodiments include a second arm. The second arm can be configured to transition between an open configuration and a closed configuration. The second arm can be biased toward the closed configuration. Movement of the second movable arm can adjust the size of the chamber and / or the size of the channel. The movable arm can be configured to non-invasively hold a nerve having a static maximum cross-sectional dimension of 0.5 mm to 4 mm within the chamber when the movable arm is biased toward the closed configuration.

[0008] In particular, the chamber can include one or more nerve relaxation spaces defined by the movable arm. The movable arm can also include one or more bending points. The distal end of the electrode can be embedded within the movable arm. A continuous through-conductor wire can extend through the hermetic housing to form the electrode.

[0009] In various embodiments, the channel is non-linear. The chamber can be sized such that the electrode curves and contacts at least 20% of the perimeter length of a nerve having a maximum cross-sectional dimension of 0.5 mm to 4 mm. The channel can be non-linear and continuously axial.

[0010] According to another embodiment, a method of stimulating a nerve provides a neuromodulation device. The device has a body including a sealed housing that houses electronics and a buffer layer that at least partially encapsulates the sealed housing. A movable arm is coupled to the body. The movable arm is configured to transition between an open configuration and a closed configuration. The movable arm is biased toward the closed configuration. A nerve stimulation chamber is at least partially defined by the movable arm. The nerve stimulation chamber is configured to hold a nerve therein. The size and shape of the chamber are adjustable by movement of the arm. A channel through which the nerve travels is at least partially defined by the movable arm. The size and shape of the channel are adjustable by movement of the arm. The channel is axially continuous along the longitudinal axis of the channel. The device may include electrodes within the chamber. The method reduces the maximum cross-sectional dimension of a nerve to define an extended nerve having a reduced cross-sectional dimension. The extended nerve is moved through the channel along the central axis of the channel. The nerve is disposed within the chamber and the cross-sectional dimension of the extended nerve increases.

[0011] In various embodiments, the nerve is stimulated using electrodes. Various adjustment signals are used to adjust the stimulation parameters.

[0012] According to another embodiment, the method stimulates a nerve. The method provides an apparatus having a body that includes a sealed housing that houses an electronic device. The apparatus 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 at rest. A nerve stimulation chamber is at least partially defined by the arm. The nerve stimulation chamber is configured to hold a nerve therein. The apparatus has an electrode within the chamber. The method reduces the maximum cross-sectional dimension of a nerve to define a stretched nerve having a reduced cross-sectional dimension. The reduction of the maximum cross-sectional dimension is less than 50% of the diameter of the non-deformed nerve. The stretched nerve is moved through the channel along a central axis such that the channel walls apply less than 6.7 kPa of pressure to the nerve at any given point. The nerve is placed within the chamber and the cross-sectional dimension of the stretched nerve increases. At least 20% of the peripheral length of the nerve is maintained in contact with the electrode.

[0013] In various embodiments, the nerve may have a different cross-sectional shape when within the chamber, but the cross-sectional area may be substantially the same as that of the non-deformed nerve.

[0014] Some embodiments may reduce the cross-sectional dimension of a nerve within the chamber to define a stretched nerve having a second reduced cross-sectional dimension. The reduction of the maximum cross-sectional dimension may be less than 50% of the maximum cross-sectional dimension. The stretched nerve may be moved through the channel along a central axis to remove the nerve from the apparatus such that the channel walls apply less than 6.7 kPa of pressure to the nerve.

[0015] Various embodiments can maintain at least 20% of the peripheral length 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 disposed within the chamber may be greater than 50% of the cross-sectional area of the undeformed nerve. In some embodiments, the cross-sectional area of the nerve within the chamber may be equivalent to the cross-sectional area of the undeformed nerve. To that end, the chamber may include a nerve relaxation space.

[0016] The arm can be movable between an open configuration and a closed configuration. The arm can be biased toward the closed configuration such that the size of the chamber and / or channel can be adjusted by movement of the arm. The arm can have one or more flexure portions such that the size of the chamber can be adjusted by flexion of the arm. The arm can include a cushioning material configured to deform at a pressure of less than 6.7 kPa such that the size of the chamber and / or channel can be adjusted by deformation of the arm. One or more arms can form an axially continuous channel through which the nerve moves. The channel can be at least partially defined by the arm. The channel can be non-linear along its central axis.

[0017] In various embodiments, the buffer layer can be formed from silicone. The package can be formed from glass, ceramic, alumina, zirconium, and / or plastic. A continuous through-conductor can extend through the package, the buffer layer, and the movable arm. The through-conductor can form an electrode. Thus, the electrode may advantageously not be welded / jointed in some cases.

[0018] 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 passage of a nerve through the channel while providing a pressure of less than 6.7 kPa to a nerve having a diameter of 1 mm to 3 mm. The movable arm is further configured to provide a pressure of less than 4 kPa to the nerve when the nerve is stimulated by an electrode within the chamber.

[0019] The movable arm may be configured to press the nerve within the chamber to deform the nerve, but not to reduce the cross-sectional area of the nerve by more than 10%.

[0020] According to one embodiment, a method adjusts the bladder function of a patient having a condition (e.g., related to overactive bladder (OAB) or stress urinary incontinence (SUI)) associated with a symptom signal (e.g., an OAB signal) generated by the patient's body. The method provides a neuromodulation device. The neuromodulation device has a body and a movable arm. The channel is defined by the body and the movable arm. The channel communicates from outside the neuromodulation device into a stimulation chamber having a stimulation electrode therein. The movable arm is movable between a closed position and an open position. The movable arm is disposed in the open position. A predetermined somatic motor nerve of the coccygeal plexus and / or the perineal plexus associated with the pelvic floor is disposed within the chamber after the movable arm is disposed in the open position. The movable arm is disposed in the closed position after the predetermined somatic motor nerve is disposed within the chamber. The method transmits a symptom adjustment signal (e.g., an SUI and / or OAB adjustment signal) to the predetermined somatic motor nerve via the electrode. The adjustment signal is configured to activate the pelvic floor in a predetermined manner to reduce the effect of the symptom signal on the spinal cord.

[0021] In some embodiments, a given somatic nerve is disposed within the chamber and contacts the electrode. By placing the movable arm in the closed position, a given somatic nerve within the chamber can be compressed, slightly deforming the somatic nerve without causing damage. For example, the nerve can be compressed by 30% without damage. In some embodiments, the nerve can be compressed by 50% without damage. The housing can include a protrusion configured to press 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.

[0022] In various embodiments, the electrode partially surrounds the nerve. The electrode can contact less than 180 degrees around the nerve. The movable arm can be biased toward the closed position. A given somatic motor nerve includes the perineal nerve, and further, the perineal nerve or the pelvic floor nerve is part of the coccygeal plexus and / or the perineal plexus.

[0023] In some embodiments, transmitting includes generating a symptom modulation signal using a signal generator and transmitting it using the electrode. The symptom modulation signal can be transmitted using one or more of wired or wireless communication media. The symptom modulation signal can have an amplitude of about 0.4 milliamperes to 4 milliamperes. The symptom modulation signal can be a periodic signal having a plurality of pulses with each pulse having a pulse duration of about 200 microseconds to 400 microseconds. The symptom modulation signal can be a periodic signal having a frequency of about 5 Hertz to 20 Hertz. The symptom modulation signal can be transmitted over a period of 10 minutes or more and 30 minutes or less in a single session.

[0024] Some embodiments can transmit a SUI modulation signal to a given somatic motor nerve via the electrode. The SUI modulation signal can have a frequency different from the frequency of the OAB modulation signal. The SUI modulation signal can be transmitted after the OAB modulation signal. The SUI modulation signal can be configured to strengthen the pelvic floor when applied via a given somatic motor nerve. The SUI modulation signal can be configured to strengthen or repair the pelvic floor.

[0025] According to another embodiment, the system regulates the bladder function of a patient having symptoms (e.g., related to overactive bladder (OAB) and stress urinary incontinence (SUI)). The symptoms are related to symptom signals generated by the patient's body. The system includes a body coupled to a movable arm. The body and the movable arm define a channel therebetween. The channel communicates from outside the body to a stimulation chamber. The movable arm is movable between a closed position and an open position. The channel has a gap with a greater depth in the open position than in the closed position. The system includes an electrode disposed within the chamber. The electrode is configured to couple to the perineal nerve. The electrode has a receiving interface configured to receive an OAB regulation signal for driving the perineal nerve. The depth of the gap in the closed position is configured to be less than about 100 micrometers to inhibit non-destructive passage of the perineal nerve into the chamber. The depth of the gap in the open position is configured to be large enough (e.g., about 0.5 millimeters to 2.5 millimeters) to allow a nerve (e.g., the perineal nerve) to pass through.

[0026] In some embodiments, the depth of the gap in the closed position is substantially zero. The system may further include a signal generator having a transmitting interface configured to communicate with the receiving interface of the electrode. The signal generator may be configured to transmit an OAB regulation signal toward the electrode via the transmitting interface and the receiving interface. The OAB regulation signal may have a set of predetermined specifications for activating the pelvic floor in a predetermined manner to reduce the effect of natural OAB signals on the pelvic floor.

[0027] In various embodiments, the electrodes and the signal generator are included as part of a kit. The signal generator may have a memory for storing a set of predetermined specifications. The set of predetermined specifications may include an amplitude of about 0.4 milliamperes to 4 milliamperes. The set of predetermined specifications may include that the OAB adjustment signal is a periodic signal having a plurality of pulses. Each pulse may have a pulse duration of about 200 microseconds to 400 microseconds. The set of predetermined specifications may include that the OAB adjustment signal may be a periodic signal having a frequency of about 5 hertz to 20 hertz. The set of predetermined specifications may include a time frame for transmitting the OAB adjustment signal. The time frame may have a duration of 10 minutes or more and 30 minutes or less in a single session.

[0028] The signal generator may be configured to transmit an SUI adjustment signal to the perineal nerve. The SUI adjustment signal may have a frequency different from the frequency of the OAB adjustment signal. The signal generator may be configured to transmit the SUI adjustment signal after the OAB adjustment signal. The SUI adjustment signal may be configured to strengthen the pelvic floor when applied via the electrodes and the perineal nerve.

[0029] Exemplary embodiments of the present invention are implemented as a computer program product having a computer-usable medium having computer-readable program code. The computer-readable code can be read and utilized by a computer system according to conventional processes.

[0030] Those skilled in the art should more fully understand the advantages of the various embodiments of the present invention by reading the following "Description of Exemplary Embodiments" described with reference to the drawings summarized immediately thereafter.

Brief Description of the Drawings

[0031]

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[0032] Note that the foregoing figures and the elements depicted in the figures are not necessarily drawn to a consistent scale or any scale. Unless the context indicates otherwise, like elements are denoted by like numerals. The drawings are for illustrative purposes primarily and are not intended to limit the scope of the subject matter of the invention described herein.

[0033] DETAILED DESCRIPTION OF THE INVENTION In an exemplary embodiment, a nerve is disposed within a stimulation chamber of a nerve modulation device. The device includes a movable arm that opens to allow passage of the nerve into the stimulation chamber. The arm closes to prevent or impede the nerve from falling out of the stimulation chamber without unduly compressing the nerve. The movable arm is configured to hold nerves of various sizes within the chamber (e.g., the chamber is sized to accommodate nerves in the range of 0.5 mm to 4 mm). In various embodiments, the arm is biased toward a closed or substantially closed position.

[0034] In addition, the device can be configured to hold nerves of different sizes in contact with an electrode within the chamber while applying a non-traumatic holding force to the nerve. The channel is similarly configured to allow the nerve to pass through the channel in response to pressure from the nerve. The pressure required to open the channel is configured to be lower than a pressure that could damage the nerve. Details of the exemplary embodiment are described below.

[0035] Various embodiments further selectively stimulate the peripheral nerves of regions having high-density small-diameter nerves using combinations of low-power stimulation directed to specific nerve targets without damaging, time-intensive, and / or traumatic surgical procedures. Prior art electrode arrays unfortunately do not provide sufficient stimulation specific to the target nerve and can cause unwanted side effects. Similarly, nerve cuffs are unfortunately often sub-optimal when coupled to nerves of inappropriate size, being limited by a pre-defined size. Further, surgical implantation methods are particularly long, invasive, and difficult to perform without damaging the nerves, especially since the size of the target nerve temporarily shrinks during implantation. The various embodiments disclosed herein advantageously deliver a selective stimulation signal via an electrode in close contact with the target nerve with a simple implantation procedure.

[0036] Furthermore, various embodiments include a nerve modulation device having a channel defined by a plurality of movable and / or deformable jaws or arms. The dimensions of the channel are adjustable to allow nerves of various sizes to enter the chamber and to secure the nerve within the chamber. Details of an exemplary embodiment are described below.

[0037] Figures 1A-4C schematically illustrate a nerve modulation device 100 configured according to an exemplary embodiment. To that end, the nerve modulation 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 hinge-coupled to the body 40 (e.g., such that the arm 50 pivots relative to the body 40).

[0038] 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 that end, the housing 48 may be formed from an elastic or deformable material. The body 40 and the movable arm 50 (or the portion of the housing 48 surrounding the movable arm 50 and the body 40) may define a chamber 101 configured to receive the nerve 200 and a channel 102 that communicates with 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 for stimulating the nerve 200.

[0039] The housing 48 encloses the package 46 of the body 40. The housing 48 includes a buffer layer 49. As is known to those skilled in the art, the package 46 encloses electronic devices and semiconductor materials therein. For example, the package 46 may include different types of circuits including a (one or more) stimulation device, a (one or more) sensor, a (one or more) communication, and / or a power circuit. In various embodiments, the package 46 may be formed from a substantially rigid material such as titanium, stainless steel, glass, ceramic, alumina, zirconium, plastic, and / or other generally acceptable hermetic packaging materials. In various embodiments, the electronic device package and the nerve / attachment electrode are integral. In various embodiments, instead of a through-pin extending from a sealed housing welded to the electrode, the through-pin forms the electrode. In such embodiments, the electrode is not welded (i.e., has no weld joint connecting the electrode to the through-pin). Instead, the through-pin forms the electrode. When the through-pin is embedded in a movable arm (e.g., silicone), it operates as a reinforcement for the flexing arm.

[0040] Package 46 forms an airtight seal around the internal electronic circuit. The electronic circuit is preferably loaded into the sealed housing 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 that could cause an electrical failure is introduced into the electronic device package 46. Second, the airtight seal ensures that the non-bio-compatible materials in which the internal electronics are formed do not leach into the body.

[0041] Preferably, package 46 is formed from a glass or ceramic material that reduces interference with the radio frequencies used for wireless power and wireless communication compared to other commonly used package 46 materials. Package 46 (also referred to as sealed housing 46) may be formed from glass wafers joined directly to each other. Alternatively, package 46 may be formed from a zirconia ceramic with brazed through connections. In various embodiments, package 46 may be sealed using laser welding of a titanium surface brazed to zirconia.

[0042] Buffer layer 49 covers package 46 and provides continuity to a second bio-compatible layer and a suitable soft surface within the human body and to the portion that contacts nerve 200. As described above, arm 50 may include an overmolded housing 46 formed of a softer material (e.g., durometer 30-50 Shore A).

[0043] Buffer layer 49 may be formed from a material configured to conform within its rest position within the body. Arm 50 and package 46 may be enclosed by housing 46, but buffer layer 49 does not cover electrode 104. Thus, housing 48 may have an opening for electrode 104 and / or EMG 42. Additionally, via 45 may be formed through the housing. In various embodiments, buffer layer 49 can enclose from about 20% to about 99% of the device.

[0044] Via 45 may extend through package 46 and / or housing 48 (including buffer layer 49). Electrodes 104 and other external electrical connections may be connected to metallized via 45. The metallized via may be formed using, among other things, a platinum through-wire. Package 46 and buffer layer 49 may be joined using RTV biocompatible silicone.

[0045] In FIGS. 1A - 2B, arm 50 is depicted in a closed or substantially closed position (collectively referred to as the closed position of the device), and the size of channel 102 is small enough such that nerve 200 cannot pass through channel 102. The arm is movable from the closed position to an open position where the size of channel 102 is large enough such that nerve 200 can pass through. In some embodiments, the open position is large enough such that the diameter of nerve 200 can contract by about 30% to less than about 50% (e.g., by stretching and / or compressing the nerve passing through the channel) and pass through the channel. As further described below, various embodiments may be configured to accept various nerve sizes. In various embodiments, arm 50 may be biased toward the closed position (e.g., by using a biased internal member 51). A medical practitioner may move arm 50 to the open position by applying a force to arm 50 (e.g., by pulling on a grippable extension 52) or by having nerve 200 itself push on arm 50. Nerve 200 may then pass through channel 102 in and out of chamber 101.

[0046] As shown in detail in FIG. 3A, 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 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 configured to be disposed relative to the concave surface of the arm 50 (as shown in FIG. 3A). The protrusion 54 and the arm 50 may be sized to prevent the arm 50 from crushing the nerve 200 in the chamber 101 beyond a preset amount.

[0047] The description herein may refer to the channel 102 formed between or defined by the arms 50, but it should be understood to include embodiments where the arms are enclosed by the housing 48. Thus, various embodiments are not limited to exposed arms 50.

[0048] FIG. 3B schematically shows an alternative embodiment where the protrusion 54 does not extend from the body (e.g., from the housing 48). Instead, the arm 50 may have the protrusion 54. Similar to FIG. 3A, the protrusion 54 and the housing 48 may be configured to prevent the arm 50 from crushing the nerve 200 in the chamber 101 beyond a preset amount. In various embodiments, to enhance retention of the nerve 200 within the chamber 101, the housing 48 may include a receiving portion 56 (e.g., a recess) configured to receive a portion (e.g., the tip) of the protrusion 54.

[0049] As shown in FIGS. 4A-4B, when the nerve 200 is received within the chamber 101, the nerve 200 is substantially prevented from moving in the X or Y directions (i.e., by the force of the arm 51 pressing on the nerve 200). Specifically, the nerve 200 is sandwiched between the nerve contact surface 58 (which may be concave) and the electrode 104. As shown, the nerve 200 may be slightly compressed. However, in some embodiments, the size of the chamber 101 is such that the nerve 200 is not compressed at all. In such embodiments, the channel 102 is sufficiently narrow in the closed position so that the nerve 200 cannot escape from or enter the channel 102 under normal use. As more clearly shown in FIG. 4A, the nerve 200 is not prevented from moving in the Z direction (other than by friction that may be caused by moving the nerve 200 through the compression region). Thus, in various embodiments, the movable arm 50 defines a chamber 101 having a first open end and a second open end when the arm 50 is in the closed configuration. The chamber 101 may also be fluidly coupled to the channel 102 defined by the movement of the arm 50. The arm 50 may move such that there is a gap that is smaller (e.g., substantially zero) than the cross-sectional dimension of the nerve 200 in the channel 102 in the closed configuration. The arm 50 may also move such that there is a gap that is larger than the cross-sectional dimension of the nerve 200 in the channel 102 in the open configuration.

[0050] In contrast to prior art nerve cuffs, it should be apparent to those skilled in the art that the electrodes 104 in various embodiments only partially surround the nerve 200. In other words, the nerve 200 has an outer circumferential segment that is contacted by the electrode 104, although not completely, but only partially.

[0051] Figure 4C schematically shows another embodiment having an extension electrode 104A. In some embodiments, the extension electrode 104A can be the second electrode 104. When disposed within the channel 102, the extension electrode 104A can stimulate the nerve 104. Additionally, the electrode 104A can be used to stimulate the nerve 200 and provide information to the operator (e.g., that the nerve 200 is not at the desired location to be stimulated within the chamber 101). In various embodiments, the electrode 104A can extend up to and / or onto the protrusion 54. In some embodiments, the chamber 101 can have the functionality of a recording chamber 101 and / or a stimulation chamber 101. For example, the recording chamber 101 can record electrical activity within the chamber 101, and the stimulation chamber 101 can induce electrical stimulation within the chamber 101. For this purpose, the electrode(s) 104 (and / or the electrode 104A) can be used to record signals from the nerve 200 and / or stimulate the nerve.

[0052] 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 manufactured using a flexible polyimide / SiC substrate with gold metallization at the ultra-microscale using established thin-film and photolithography techniques. In another example, the device 100 can be fabricated from SU-8 or other such polymers using commonly used microfabrication and photoresist techniques.

[0053] 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 stimulation device (sometimes collectively referred to as a “signal generator”). The device 100 can optionally include circuitry for communicating with the signal generator. For example, the communication circuitry can facilitate magnetic inductive coupling or direct conductive connection (e.g., via a wire or other wired electrical interface).

[0054] Chamber 101 is configured to receive a nerve 200 (e.g., a human somatic motor nerve). Nerve 200 can include a plurality of axons, nerve fibers, nerve bundles, fascicles, or other similar neuroanatomical structures. However, it should be understood that nerve 200 is preferably an intact nerve or a partially functioning nerve. For example, an intact nerve needs to have functional presynaptic and postsynaptic terminals and be able to functionally propagate action potentials. For example, in some embodiments, nerve 200 can 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 can have an average diameter in the range of about 50 μm to about 4 mm, about 50 μm to about 3.5 mm, or any other range between the exemplary sizes described above.

[0055] In some embodiments, chamber 101 can be generally cylindrical in shape, with both ends of the cylindrical chamber 101 open to allow the nerve 200 to exit longitudinally from chamber 101 towards the presynaptic and postsynaptic terminals of nerve 200. The cylinder includes a circular cross-sectional shape, but it should be understood that chamber 101 can also include a triangular, square, pentagonal, hexagonal, or polygonal cross-sectional shape having n sides while maintaining a generally three-dimensional structure similar to a cylinder or pipe with open ends and operable to receive nerve 200. Some embodiments of chamber 101 may not have a specific cross-sectional shape and instead may have an irregular cross-sectional shape.

[0056] The chamber 101 can be in fluid communication with the outer surface 103 of the device 100 and the second (opposite) outer surface 103 in some embodiments. Specifically, the first and second outer surfaces 103 in this example are disposed between the first outer surface and the second outer surface and are on both sides of the device 100 and the chamber 101 that are in fluid communication with the respective opposing first and second outer surfaces 103 of the device 100.

[0057] As a three-dimensional region, the chamber 101 has a length, a depth, and a height. The length of the chamber 101 corresponds to the z-axis that transversely traverses longitudinally along the nerve 200 extending through the device 100. The depth of the chamber 101 corresponds to the x-axis and the height corresponds to the y-axis. In some embodiments, the chamber 101 can 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, the chamber 101 can have an average length of about 50 μm to 11 mm (e.g., about 2 mm). In some embodiments, the chamber 101 can 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.

[0058] The various dimensions of the chamber 101 are described below. It is assumed that the dimensions of the chamber 101 are the dimensions when the chamber is in the closed position. As described above, the chamber 101 is partially defined by the movable arm 50. Thus, the chamber 101 has a closed configuration (also referred to as the closed position) and an open configuration (also referred to as the open position). The chamber also has an intermediate configuration between the open configuration and the closed configuration, but the terminal configurations are described herein. It is assumed that the dimensions of the chamber 101 described herein refer to the closed configuration unless otherwise required by the context.

[0059] As described above, the depth and height of the chamber 101 can be considered to correspond to the cross-sectional dimensions of the xy plane orthogonal to the z-axis of the chamber 101. For example, the cylindrical chamber 101 can have a depth and height corresponding to the diameter of the chamber 101. The diameter of the non-cylindrical chamber 101 can be measured by averaging the distances of the measured values that intersect the center point of the cross-section of the chamber 101, and the center point is arranged on the z-axis extending through the center of the chamber 101. In some embodiments, the chamber 101 can have an average diameter of less than about 10 mm. In some embodiments, the chamber 101 has an average diameter of 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.

[0060] In some embodiments, the chamber 101 has an average diameter that is substantially the same as or 10% smaller than the average diameter of the target nerve 200. In some embodiments, the average diameter of the chamber 101 is 5% or less larger or 5% or less smaller than the average diameter of the target nerve 200. In some embodiments, the average diameter of the chamber 101 is 15% or less larger or 15% or less smaller than the average diameter of the target nerve 200. For example, in the case of the target nerve 200 having an average diameter of about 80 μm, the device 100 can have an average diameter of about 56 μm or more and 104 μm or less. In some embodiments, the chamber 101 has an average diameter of 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 the target nerve 200.

[0061] In some embodiments, channel 102 is defined by two walls that can provide an upper boundary and a lower channel boundary. Optionally, 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. Thus, the distal end of channel 102 is open to chamber 101. In some embodiments, chamber 101 is unrestrictedly or always open to channel 102 such that the distal opening of channel 102 into chamber 101 does not close. Further, channel 102 can connect the interior of chamber 101 to the outer surface 103 of device 100. Thus, in this embodiment, chamber 101 is essentially always in communication with the outer surface 103 of the device via channel 102. For example, chamber 101 always remains open to the channel and channel 102 always remains open to the outer surface.

[0062] The various dimensions of channel 102 are described below. It is assumed that the dimensions of channel 102 refer to when channel 102 is in the closed position. As described above, channel 102 is partially defined by an arm 50 that is movable. Thus, channel 102 has a closed configuration (also referred to as the closed position) and an open configuration (also referred to as the open position). Channel 102 also has an intermediate configuration between the open configuration and the closed configuration, but the terminal configurations are described herein. It is assumed that the dimensions of channel 102 described herein refer to the open configuration, unless otherwise required by context. This is in contrast to the description of chamber 101, which generally refers to the dimensions of the chamber in the closed configuration.

[0063] As a three-dimensional region, channel 102 has a length, a height, and a width (also referred to as a gap or an opening). Similar to the length of chamber 101 described above, the length of channel 102 corresponds to a measurement along the z-axis that transversely extends longitudinally along nerve 200. The length can be measured at any point along channel 102 between the distal end of the channel opening into chamber 101 and the proximal end of the channel opening 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 the open position to the closed position.

[0064] In some embodiments, channel 102 can have an average length of at least 100 μm. In some embodiments, channel 102 can 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 can have an average length of about 100 μm to 10 mm. In some embodiments, channel 102 can 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 (for example, in one embodiment of a device having a battery).

[0065] The height of channel 102 corresponds to the distance measured between the distal and proximal openings of channel 102, and the distance is measured along a virtual centerline that is equidistantly disposed between each channel wall. In some cases, the height can be a linear measurement. For example, in some cases, channel 102 is a linear channel 102. In some cases, channel 102 may be non-linear, and a non-linear channel includes one or more bends, curves, or flexures of the channel wall (e.g., from protrusion 54). Thus, in some cases, the height of non-linear channel 102 can be measured by measuring the distance along the virtual centerline of channel 102 between the distal and proximal openings of channel 102, and the distance along each flexure of non-linear channel 102. For example, in some embodiments, channel 102 can include an "L" shape where the height measurement of channel 102 includes a 90-degree bend and each end of the "L" corresponds to the distal and proximal openings of the channel. In an exemplary channel having a 90-degree bend, the height can be measured by summing the distances along the virtual centerline of the channel to the point where the virtual lines of each arm of the "L" within channel 102, which extends between the proximal and distal openings of channel 102, intersect. The shape of the channel can also include other configurations such as a "T" shape, a "Z" shape, and an "S" shape.

[0066] In some embodiments, channel 102 can have an average height of about 100 μm to 5 mm (e.g., 4.5 mm). In some embodiments, channel 102 can 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.

[0067] The width of the channel 102 corresponds to the measured value of the channel 102 disposed in the xy plane orthogonal to the z-axis as described above. The width of the channel 102 can be made constant so that the width of the channel 102 does not change between the proximal opening and the distal opening of the channel 102. That is, in some embodiments, the width of the channel 102 includes a variation of less than 10% of the average width over the entire height of the channel 102. In some cases, the channel 102 includes a variation of less than 5%, less than 3%, or less than 2% of the average width along the entire height measurement of the channel 102. In some cases, the width can be determined by measuring the shortest distance between the body 40 (e.g., the housing 48) and the arm 50.

[0068] In some embodiments, the width of the channel 102 is narrower than the diameter of the target nerve 200. For example, in some embodiments, the width of the channel 102 can be at least 5% narrower 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% narrower than the diameter of the nerve 200. In some embodiments, the width of the channel 102 can be 60% or less narrower than the diameter of the target nerve 200. In other embodiments, the width of the channel 102 can be 50% or less narrower than the diameter of the target nerve 200. In some embodiments, the width of the channel 102 can be about 5% to 60% narrower 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% narrower than the diameter of the target nerve 200.

[0069] Further, similar to the chamber 101 described above, the channel 102 can have an open end that is in fluid communication with the open end of the chamber 101 such that when the channel 102 is in the open position, the longitudinal cross-section of the nerve 200 can be slid, moved, or inserted into the chamber 101 through the channel 102. Thus, the channel 102 is configured to receive the target nerve 200. Further, 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 into the interior of the chamber 101 at the distal end of the channel, and the channel can extend to the third outer surface 103 along the height of the channel at the proximal end of the channel while maintaining fluid communication with the first and second outer surfaces 103 on opposite sides of the device 100 corresponding to opposite ends of the z-axis.

[0070] As described above, the device 100 has at least one electrode 104 within the chamber 101. The electrode 104 can include various types of electrodes, including, among others, fiber electrodes or planar electrodes, thin-film electrodes, or needle electrodes. As an example, the electrode 104 can be implemented as a thin-film electrode having a recording or stimulation surface within 100 - 2000 μm2 or within 50 μm from the outer surface of the nerve 200 when coupled within the chamber 101. A needle electrode within the chamber can have a needle-shaped recording and / or stimulation surface that can penetrate the surface of the nerve 200 when within the chamber 101. An electrode that penetrates the nerve within the chamber 101 can stimulate and / or record within the nerve, thereby providing greater selectivity and / or resolution when recording and / or stimulating. Additionally, the electrode 104 can be disposed on any of several other surfaces within the chamber 101, including the top surface, bottom surface, and / or side chamber surfaces.

[0071] When chamber 101 has multiple electrodes 104, combinations of electrode types can be used. For example, both planar electrodes and / or needle electrodes can be used in recording and / or stimulation chamber 101. In particular, the (one or more) electrodes 104 can be monopolar, bipolar, tripolar, or multi-electrode array electrodes. In some cases, multiple electrodes 104 can be configured in a tripolar configuration, which should improve neural specificity and / or selectivity while simultaneously reducing external biological noise.

[0072] As described above, electrode 104 can be formed, at least in part, from one or more conductive metals. For example, the electrode can be formed, at least in part, from gold, titanium nitride (TiN), iridium oxide (IrO), iridium, carbon nanotubes, graphene, graphene oxide, and / or platinum (Pt). Electrode 104 can, in some cases, have a charge injection capacity of about 0.1 mC / cm2 or more. Further, 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.

[0073] In some embodiments, electrode 104 is about 25 μm 2 ~25 mm 2 and can have a stimulation surface area and / or a recording surface area. In some cases, the electrode is about 100 μm 2 ~1 mm 2 or about 100 μm 2 ~0.5 mm 2 and includes a stimulation surface area and / or a recording surface area.

[0074] Exemplary embodiments use a predetermined neuromodulation technique to selectively activate one or more pelvic floor muscles. In particular, those pelvic floor muscles can include the cremaster muscle, the bulbourethral gland muscle (Bgm), the ischiocavernosus muscle (Ism), the bulbocavernosus muscle (Bsm), the pubococcygeus muscle (Pcm), the iliococcygeus muscle (Icm), the coccygeus muscle (Cgm), or the puborectalis muscle (Prm). However, preferably, the pubococcygeus muscle is driven using the perineal nerve. Alternatively, the pubococcygeus muscle can also be driven using the pubococcygeal branch. In some embodiments, the pelvic floor muscles can be neuromodulated or stimulated simultaneously or independently from one or more other pelvic floor muscles. In some cases, the pelvic nerves can include any nerve, nerve bundle, fascicle of nerve fibers, or nerve pathway that innervates the pelvic floor muscles or pelvic viscera, which can include the pudendal nerve, the clitoral nerve, or the dorsal nerve of the penis, or any branches of these or other nerves within the pelvis. In various embodiments, some embodiments can be used to assist in treating pelvic organ prolapse by stimulating the distal terminal branches of the pudendal nerve (e.g., perineum, inferior rectum) and / or the terminal branches of the levator ani nerve. Further, some embodiments can be used in veterinary applications for stimulating the nerves of an animal.

[0075] It should be understood that the above-described device 100 is an example of a neuromodulation device that can be used to stimulate appropriate somatic nerves. For example, two or more devices 100 can also be used to stimulate two or more pelvic floor muscles or pelvic viscera. Further, since the device 100 can record and / or stimulate, two or more devices can be used independently to record and stimulate the same pelvic floor muscle, or one device can be used to record and stimulate the pelvic floor muscle or pelvic viscera.

[0076] FIG. 5 schematically shows another embodiment of the apparatus 100 according to an exemplary embodiment. Note that this figure has different reference numbers for the same components as above, but similar components have the same or similar functions. As shown, the apparatus includes a battery-driven or other driven pulse generator and an electronic controller 1901 connected to an electrode 1905 via a conducting wire 1903. As illustrated, the electrode is part of a chamber 1907 of the neuromodulation device 1911. As illustrated, 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 narrower than the diameter of the target nerve in the closed configuration and / or the open configuration. Thus, the target nerve can be temporarily and reversibly compressed or stretched and slid through the channel until the target nerve is held within the chamber 1907. In some embodiments, the chamber 1907 may have a diameter larger than the nerve so that the nerve is not compressed or stretched within the chamber 1907. Alternatively, the chamber 1907 may have a diameter smaller than the nerve. Thus, in such embodiments, at least a portion of the nerve extends within the channel 1909 while a substantial portion of the nerve is housed within the chamber 1907. Further, the chamber 1907 may provide a separate fluid environment that allows for targeted specific stimulation of a portion of the nerve held within the chamber 1907.

[0077] FIG. 6 schematically shows a wireless neuromodulation device and an external system according to an exemplary embodiment of the present invention. Similar to FIG. 5, this figure has different reference numbers for the same components as above, but similar components have the same or similar functions. The device has an external battery-powered or other powered pulse generator and electronic controller 2001 that includes a coil for transmitting power, data, and / or adjustment signals to the wireless neuromodulation device 2013. In particular, an electromagnetic field 2003 can couple the pulse generator and electronic controller 2001 to the wireless neuromodulation device 2013. Corresponding electronics and magnetic induction coil 2005 within the neuromodulation device 2013 can be connected to a conductive material used as the (one or more) electrodes 2007. The electrodes 2007 can form part of the chamber 2009. As described in other embodiments, the neuromodulation device of this figure can include a chamber 2009 configured to receive a nerve and a channel 2011 (e.g., an expandable gap) through which the nerve can pass when disposed within the chamber 2009.

[0078] FIG. 7 schematically shows another wireless embodiment of the system. Similar to FIGS. 5 - 7, this figure has different reference numbers for the same components as above, but similar components have the same or similar functions. To that end, an external battery-powered pulse generator and electronic controller 2101 having a coil are configured to transmit power, data, and / or adjustment signals to the neuromodulation device 2115. An electromagnetic field 2103 couples to the coil 2105 of the neuromodulation device 2115. In some embodiments, the electronics and coil 2105 can be implanted separately and spaced apart from the stimulation element of the neuromodulation device 2115. The position 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.

[0079] Furthermore, the configuration of the separate electronic device and coil 2105 can result in reduced battery requirements and applied voltage and / or amplitude. The lead wire 2107 can couple the electronic device and coil 2105 to the neuromodulation device 2115, and more specifically to the electrode 2109 that can be located within the chamber 2111. Similar to 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 disposed within the chamber 2111.

[0080] Among other advantages, connecting an implanted electronic device to a neuromodulation device with a receiving coil effectively isolates the receiving coil. Thereby, a medical practitioner can implant the receiving coil in the same position and orientation relative to the body's hard tissue structures regardless of where the electrode and neuromodulation device are located. This consistency in the position and orientation of the receiving coil is expected to provide more consistent, efficient, and reliable coupling and induction in the implanted coil and electronic device. This can help avoid variability in stimulation or variability in requirements for the position or orientation of the external coil.

[0081] The inventors have discovered, based on their experiments, that stimulation of the pelvic floor muscles can activate sensory fiber types not previously associated with urinary incontinence. Specifically, this includes the large myelinated sensory pathways of the proprioceptive types Ia and Ib. In that case, using appropriate parameters / specifications, these sensory pathways can be targeted for selective neuromodulation to activate previously unknown sensory pathways to the central nervous system, including the spinal cord and brainstem pathways involved in bladder and bowel control.

[0082] Therefore, the inventors were surprised to learn that acute electrical stimulation of the bulbocavernosus nerve in certain animals significantly increases the maximum urethral pressure and micturition efficiency in proportion to the stimulation frequency. Acute stimulation is sufficient to induce a three-fold increase in urethral pressure and urine volume, indicating that activation of this perineal nerve strengthens the urethral sphincter and supports voluntary control and micturition efficiency. This result confirmed the ability of a small wireless stimulation device as a strategy to reverse SUI-like characteristics in aging and multiparous rabbits for effective pelvic floor muscle contraction.

[0083] The coccygeal plexus is anatomically and functionally different compared to the pelvic plexus, which includes the pudendal nerve. Therefore, sacral nerve modulation (SNM), percutaneous tibial nerve stimulation (PTNS), and pudendal nerve stimulation (PNS), all parts of the pelvic plexus mainly target the same sacral (S2-3) level of the spinal cord, and the axons of the sacral nerves or peripheral nerves are anatomically and functionally mixed with pain neurons, mechanoreception motor neurons, proprioceptive neurons, and autonomic neurons. The inventors believe, but have not confirmed, that the mechanisms of action of SNM, PTNS, and PNS for the treatment or urgency urinary incontinence involve the regulation of mechanosensory afferent fibers.

[0084] In contrast, the inventors found that the axons innervating the pelvic floor muscles are innervated by either the pelvic plexus or the coccygeal plexus, are anatomically and functionally more homogeneous, and are mostly composed of motor somatic efferents and proprioceptive (Ia / Ib) sensory afferents, which pass through the anterior (S2-3) and / or more posterior (S4-5) spinal cord levels, respectively, and enter the spinal cord through the perineal nerve and / or the levator ani nerve. However, proprioceptive axons ascend all the way up to lumbar (L) 7, connecting the function of the PFM to the function of the bladder and other pelvic organs. Thus, the inventors discovered that stimulation of the proprioceptive sensory afferents also inhibits the activity from the bladder, and thus discovered that such stimulation could be a useful treatment for overactive bladder syndrome. The exemplary embodiment selects the motor branch of the perineal nerve that controls the pubococcygeus muscle. See FIG. 8A for details.

[0085] Figure 8B is a diagram showing the innervation pattern of the target nerve according to an exemplary embodiment of the present invention. As shown, the pubococcygeus muscle is innervated by branches of the perineal plexus and the coccygeal plexus at different ends. The pelvic nerve is a branch of the perineal plexus that innervates the anterior Pcm, but it also receives innervation from the pubococcygeal nerve that branches from the levator ani muscle. The innervation ratio is based on two references listed on the slide.

[0086] Various embodiments can, among other things, treat female sexual dysfunction, male erectile dysfunction, fecal incontinence including but not limited to sacral nerve stimulation, overactive bladder / urge incontinence including but not limited to sacral nerve or tibial nerve stimulation, chronic pelvic pain by activating mechanoreceptor or proprioreceptor fibers that compete with nociceptive signals or by directly blocking the signals of pain fibers, headache, pain management including somatic (i.e., muscle, limb) and visceral, blood pressure management, sleep apnea, stimulation for nausea, stimulation for tremors, and / or stimulation of the vagus nerve, sacral roots and anterior roots for various uses by connecting and stimulating the nerves. Various embodiments can stimulate various nerves according to the stimulation parameters provided herein (e.g., for OAB and SUI), and according to the same or different parameters (e.g., as used for OAB and / or SUI) for other treatments.

[0087] Figure 9 shows a neuromodulation process according to an exemplary embodiment. Note that this process has been simplified from the longer processes typically used. Thus, the process is likely to have many steps that those skilled in the art may use. Additionally, some of the steps may be performed in an order different from the order shown. Additionally or alternatively, some steps may be performed simultaneously. Thus, those skilled in the art can modify the process as appropriate.

[0088] The process uses at least one "regulation signal" to neuromodulate appropriate motor nerve branches and proprioreceptive nerve branches from either the coccygeal plexus and / or the perineal plexus, which in this example is the perineal nerve. These regulation signals are called as follows: 1) "OAB regulation signal" targeted at managing overactive bladder syndrome, and 2) "SUI regulation signal" aimed at managing stress urinary incontinence.

[0089] Thus, the process of FIG. 9 starts with step 1000 of setting the specifications of the regulation signal. In various embodiments, the regulation signal can be an OAB regulation signal and / or an SI regulation signal. These specifications can be stored in a database, memory, or other storage medium for use in later steps. In particular, such a location can be part of the device 100 itself, part of the signal generator, somewhere in a local area network (e.g., a corporate network), or somewhere in a larger wide area network (e.g., the Internet). The inventors have determined, using calculations and experiments, that the subsequent specifications should result in satisfactory outcomes.

[0090] The process uses at least one "regulation signal" to neuromodulate appropriate nerves, such as the somatic nerves of the coccygeal plexus, which can be the perineal nerve in this example. These regulation signals are called as follows: "OAB regulation signal" - stimulation parameters targeted at managing overactive bladder syndrome, and "SUI regulation signal" - stimulation parameters aimed at managing stress urinary incontinence.

[0091] Specifically, the OAB regulation signal can have one or more sets of the following specifications for humans: an amplitude of about 0.4 milliamperes to 1 milliampere, each pulse having a pulse duration of about 200 microseconds to 400 microseconds (when the OAB regulation signal is a periodic signal), A frequency of about 5 Hz to 20 Hz (when the OAB regulation signal is a periodic signal), and A duty cycle of about 5% to 100% (for example, more specifically, about 8% to 12%). Stimulation pulses of about 10 to 20 seconds followed by about 2.5 minutes of off, repeated at least 3 to 4 times within a single session A duration for transmitting an OAB regulation signal of 10 minutes or more and 30 minutes or less in a single session.

[0092] These values can be appropriately scaled for different mammals. Additionally, these values can be adjusted as a function of the number of treatments per day or per week, the individual, and / or the disease severity.

[0093] The SUI regulation signal can have one or more sets of the following specifications for humans: An amplitude of about 0.5 milliamperes to 2 milliamperes, Each pulse having a pulse duration of about 200 microseconds to 400 microseconds (when the OAB regulation signal is a periodic signal), A frequency of about 60 Hz to 100 Hz (when the OAB regulation signal is a periodic signal), and A duty cycle of about 5% to 100% (for example, more specifically, about 8% to 12%). Stimulation pulses of about 10 to 20 seconds followed by about 2.5 minutes of off, repeated at least 3 to 4 times within a single session A duration for transmitting an SUI regulation signal of 30 seconds or more and 120 seconds or less in a single session.

[0094] As another example, the OAB regulation signal can have one or more sets of the following specifications for humans: An amplitude of about 0.4 milliamperes to 1 milliamperes, Each pulse having a pulse duration of about 200 microseconds to 400 microseconds (when the OAB regulation signal is a periodic signal), A frequency of about 5 Hz to 20 Hz (when the OAB adjustment signal is a periodic signal), and A duration for transmitting an OAB adjustment signal of 10 minutes or more and 30 minutes or less in a single session.

[0095] These values can be appropriately scaled for different mammals. Additionally, these values can be adjusted as a function of the number of treatments per day or per week, the individual, and / or the disease severity.

[0096] The SUI adjustment signal can have one or more sets of the following specifications for humans: An amplitude of about 0.4 milliamperes to 4 milliamperes, Each pulse having a pulse duration of about 200 microseconds to 400 microseconds (for example, when the OAB adjustment signal is a periodic signal), A frequency of about 60 Hz to 100 Hz (when the OAB adjustment signal is a periodic signal), and A duration for transmitting an SUI adjustment signal of 30 seconds or more and 120 seconds or less in a single session.

[0097] Similar to the specifications of the OAB adjustment signal, these values can be appropriately scaled for different mammals. Additionally, these values can be adjusted as a function of the number of treatments per day or per week, the individual, and / or the disease severity.

[0098] Generally, the symptom adjustment signal for pelvic floor neuromodulation can have a frequency of about 2 Hz to about 100 Hz. The nerve block signal can use a higher frequency such as about 1 kHz to about 40 kHz. However, some embodiments may use a low frequency (for example, less than 10 Hz for nerve block).

[0099] Advantageously, both the afferent adjustment signal and the efferent adjustment signal can be transmitted on the same nerve using the same neuromodulation device 100. [Table 1]

[0100] Experiments by the inventors have shown that centrifugal stimulation of the inferior rectal nerve using the above stimulation parameters can close the external secondary anal sphincter.

[0101] Details of the various adjustment signals that can be used are described in co-pending U.S. Patent Application No. 17 / 985,843, which is hereby incorporated by reference in its entirety.

[0102] The process proceeds to step 1001, where the device 100 transitions to the open configuration. As described above, the device 100 has an open configuration and a closed configuration. FIGS. 10A and 10C schematically show various embodiments of the device 100 in the closed configuration. In the closed configuration, the depth of the channel 102 (also called the gap) between the movable arm 50 and the housing 48 (or the protrusion 54) is small enough so that the target nerve cannot enter the chamber 101 through the channel 102 without damage. Thus, by transitioning to the open configuration, the nerve can enter the chamber.

[0103] FIGS. 10B and 10D schematically show various embodiments of the device 100 in the open configuration. In various embodiments, the opening of the channel may have a tapered or "V-shaped" 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 enter the chamber 101 through the channel 102. It should be understood that the open configuration may be, but does not necessarily have to be, the maximum open position. That is, the device may be in the open configuration even if the arm 50 can be further moved to widen the gap. In various embodiments, the size of the gap can be determined by measuring the shortest distance between the housing 48 and the arm 50.

[0104] In various embodiments, the size of the gap in the closed configuration is less than or equal to the diameter of the target nerve 200. For example, the dimensions of the closed gap may be configured to be 30-50% smaller than the target nerve 200. Various embodiments may have a gap in the closed configuration of from about 0 mm to about 0.7 mm, such as 0.5 mm. Various embodiments may have a gap in the open configuration of about 0.75 mm, 1.75 mm, or 2.75 mm.

[0105] Transition to the open configuration can be achieved by the healthcare provider pulling on the movable arm 50 to create a gap and / or enlarging the size of the gap sufficient to pass the nerve (or stretched nerve), pressing a button, or using the nerve itself to open the channel. In some other embodiments, the arm 50 can be operated electromechanically (e.g., by pressing a button). In some other embodiments, the biased arm 50 (e.g., a polymeric "spring load" within its elastic range, the elastic properties of the material itself, addition of a spring, etc.) may be pre-opened or opened using a delivery system or instrument.

[0106] In some other embodiments, the force of the nerve pressing on the biased arm 50 is sufficient to move the biased arm 50 and allow the nerve to pass through. In various embodiments, the healthcare provider may stretch the nerve to reduce its diameter, and the nerve may fit into the opening of the channel 102. By reducing the diameter of the nerve, the healthcare provider can slide the nerve into the channel 102, and the channel opens slightly (i.e., to the open configuration) to allow passage of the nerve. After the nerve has passed through the channel 102, the healthcare provider stops the channel and returns it to its closed configuration, holding the non-stretched nerve within the chamber 101. In the chamber 101, the healthcare provider stops stretching the nerve, and thus the nerve is held within the chamber.

[0107] The process proceeds to step 1002, where the electrode is coupled to the somatic nerve (e.g., the perineal nerve) as described above. Thus, the healthcare provider can align the nerve with channel 102 and place the perineal nerve through channel 102. The nerve 200 can then be secured within chamber 101.

[0108] In some embodiments, the nerve 200 can be stretched to have a smaller cross-sectional dimension so that it can pass through channel 102. When the nerve 200 is stretched for a short period of time, it is released at the bottom of the chamber in a “free” region where the nerve can recover and return to approximately its original shape and size. However, in some embodiments, the gap in channel 102 is large enough to allow the unstretched nerve 200 to pass through. The nerve can relax or return to its normal state depending on its size when it is secured within chamber 101.

[0109] The process then proceeds to clip 1003, and the device transitions to a closed configuration. As previously described, the arm 50 can be biased to close. Thus, the healthcare provider only needs to remove the force used to open the arm 50, and the biasing force closes channel 102 and moves to the closed configuration. As previously described, the closed configuration does not necessarily have a zero gap. In some embodiments, the gap is small enough to prevent the nerve from falling out of chamber 101.

[0110] In various embodiments, the movable arm 50 can be spring-loaded. Thus, the movable arm mechanism may be referred to as a “clip” that allows the nerve to be stationary within the chamber-like space but is held in place by a gentle holding force that presses the nerve against the electrode. As the nerve descends through the channel, the spring force of the fixed arm 50 returns toward the rest 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 within the chamber before returning to the rest position.)

[0111] 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 whose cross-sectional dimensions vary by up to 400% or more (e.g., from a 1 mm nerve to a 4 mm nerve). In various embodiments, instead of the channel defined by the spring-loaded arm being "held" in place by a clip, the orientation of the channel chamber is utilized to accommodate the extended nerve 200, so that the spring load does not apply excessive stress to the nerve. The nerve 200 descends into the channel (e.g., a variable-width channel) according to the position of the spring-loaded arm and rests within a chamber area that is also variable with respect to the size of the nerve due to the same spring-loaded arm. When the channel is gently closed and held by the spring force, the mechanism of the chamber wall is oriented to help guide the nerve and maximize contact with the electrode.

[0112] Thus, it should be understood that in the closed configuration, the nerve 200 can be slightly compressed by the arm 50 (e.g., by the nerve contact surface 58). However, in some other embodiments, the nerve 200 is not compressed by the arm 50 and can simply be confined within the chamber 101.

[0113] As described above, the nerve is preferably directly and conductively coupled to the electrode 104. Thus, it is preferred that there are no other non-negligible organic components of the patient present between the nerve and the device 100 (e.g., between the electrode 104 and the nerve). Some embodiments have a coating or other structure on the electrode 104 and can have a direct connection or bond with the nerve.

[0114] Next, the process proceeds to step 1004. With the nerve firmly within chamber 101, the signal generator may initiate transmission of the OAB regulation signal to device 100, electrode 104, and the perineal nerve (step 1004). Over time, this signal reverses and normalizes the OAB symptoms. The stimulation activates the pelvic floor in a predetermined manner. However, during the experiments, the inventors were surprised to discover that this signal appears to reduce the effect of the natural OAB signal on the pelvic floor. Specifically, the patient's body naturally transmits an OAB signal (referred to as the "natural OAB signal"), which is part of the patient's mechanism that causes 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, dulling or otherwise reducing the effect of the natural OAB signal.

[0115] As described above, in a single session, the method may transmit an OAB regulation signal to the perineal nerve for about 10 - 30 minutes. As described above, this timing can be finely adjusted according to the patient, severity of the disease, etc. After the OAB signal treatment is completed, the process may then proceed to optional step 1006 to treat SUI. Additionally or alternatively, the process may transmit an FI signal to treat FI. Specifically, if the patient is also suffering from SUI, the method may transmit an SUI regulation signal to the perineal nerve for 30 - 120 seconds in this session. Additionally or alternatively, the process may transmit an FI signal to treat FI. Other embodiments may reverse the order of step 1004 and step 1006.

[0116] Next, the process proceeds to step 1007 to remove the nerve from chamber 101. In some embodiments, it may be permanently implanted and thus this step may be omitted. However, advantageously, in various embodiments it can be easily removed. As described above, the device transitions to an open configuration. In some embodiments, a medical practitioner may do this using an instrument. In some other embodiments, the nerve may be extended by the medical practitioner and pass 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.

[0117] While various embodiments refer to a movable arm that transitions between an open configuration and a closed configuration, some embodiments may have a non-movable or fixed arm. In such embodiments, channel 102 may be configured such that the nerve can pass through the channel non-invasively when the nerve is extended. To that end, the material of arm 50 (e.g., a buffer layer) may be soft enough that it deforms to allow passage of nerve 200.

[0118] Part or all of this process may be implemented in hardware, software, or both. For example, part or all of this process may be implemented using a custom application-specific integrated circuit, FPGA, microcontroller, or other logic, along with software (e.g., firmware), and integrated with the rest of the system.

[0119] Accordingly, the inventors have discovered that both OAB and SUI can be treated via a somatic nerve (e.g., the perineal nerve) that is relatively easy to access. Advantageously, this nerve is very small and thus requires far less power than is required for many other conventional nerve stimulation systems.

[0120] Figure 11 schematically shows a close-up view of the arm 50 according to an exemplary embodiment of the present invention. The device is shown in a closed configuration. As described above, the closed configuration is designed to gently hold the nerve 200 in the chamber where the bilateral electrodes 194 are located. The advantage of this gentle holding force is to maintain direct contact with the nerve 200 either on the wall 66 or the floor 65 of the chamber 101 where the electrode 104 is located, and to reduce the channel 102 size for the smaller diameter nerve 200 size. In some embodiments, the wall 66 can have an overall height from the floor to the top of the channel of 1400 μm. The shape and size of the electrode 104 can be formed as a curved "L" shape to facilitate direct contact regardless of whether the nerve 200 is larger or smaller in size range.

[0121] The main protrusion 62 of the spring-loaded fixed arm 50 has two purposes. The first is to provide a narrowed channel 102 width to help fix the largest diameter nerve 200 in the chamber 101 after descending through the channel 102. The second is to provide a gentle resistance to the movement of the nerve 200 to hold the nerve within the electrode 104. The angle of this protrusion 62 is angled to gently urge the nerve 200 towards the electrode. In various embodiments, the protrusion 62 can have a length of 430 microns (micrometers). The protrusion 62 can be paired with the bilateral electrodes or angled electrodes 104 (see, for example, FIG. 16) to accommodate changes in the angle of the spring-loaded fixed arm 50 as the size of the nerve changes. The smaller diameter nerve 200 is urged downward towards the horizontal portion of the electrode. The largest diameter nerve 200 is urged closer to the vertical portion as this angle changes with respect to the size of the nerve. The breakdown of these angles and distances for nerve sizes having a diameter of 100 μm to 400 μm will be outlined below.

[0122] In various embodiments, the spring-loaded fixation arm 50 can be mainly composed of an elastomeric material such as silicone or plastic. Various embodiments can form at least a portion (e.g., the outer coating) of the arm 50 from a Shore A durometer material of 30 to 50. Additionally, while a soft neural interface material such as silicone is ideal, the spring-loaded arm 50 can have overmolded or insert-molded components embedded in the silicone to provide additional spring force, especially in larger applications. Some options for this insert-type component are nitinol springs, stainless steel springs, other elastomeric materials, or overmolded springs, and other similar materials of alternative durometers. Additionally, layers of various materials with different elastomeric materials can also provide the necessary force. The materials are preferably biocompatible for long-term implants. Some embodiments can form the arm from materials such as silicone, polyurethane, embedded nitinol, and / or stainless steel springs.

[0123] A relaxation space 64 for nerve swelling can also be included on both sides of the electrode 104. The nerve 200 is flexible and behaves as if it were more balloon-like than a cable. When the nerve 200 is traumatized during implantation, the nerve swells and expands using the relaxation space 64 so as not to receive sufficient pressure to cause further damage. During swelling, or in the case of temporary swelling beyond the capacity of the clip to accommodate changes in nerve size, one or more relaxation spaces 64 are present for the nerve to expand to ensure that the nerve is not further damaged. This relaxation space 64 provides a relaxation region for swelling or pressure increase without interfering with electrode-nerve contact.

[0124] FIG. 12 schematically shows multiple orientations of the device body and the orientations of the channels / chambers according to an exemplary embodiment of the present invention. The orientations of channel 102 and chamber 101 can be horizontal, vertical, or at any angle with respect to the housing 48 / body 40 of the neuromodulation device. Additionally, channel 102 and chamber 101 can be centered around or disposed at one end of body 40 as desired to meet various anatomical requirements. Alternatively, some embodiments can separate the channel / chamber structure from the body 40 of the implant and utilize this at the end of a lead wire or extension lead wire to improve the implantation time of a conventional nerve stimulation device.

[0125] FIG. 13 schematically shows a device having multiple electrodes 104A - 104D and chambers 101A - 101D according to an exemplary embodiment. The various chambers 101A - 101D can correspond to various nerve 200 sizes. FIG. 13 also shows different orientations of channel 102 with respect to the body 40 of the device. The bilateral electrodes 104A - 104D can be disposed within each chamber 101A - 101D.

[0126] By having a series of channels 102A - 102D and chambers 101A - 101D (e.g., gradually decreasing in size), advantageously, an extended nerve 200 can enter the appropriate chambers 101A - 101D based on the nerve size. This arrangement can accommodate a wider range of nerve sizes. The increased ridges provide a force to push the nerve 200 into the electrodes located in the chamber, but prevent or inhibit a larger - diameter nerve from passing through to a smaller chamber 101, and at the same time prevent or inhibit a relaxed nerve from exiting the chamber in which it currently resides. Additionally or alternatively, some embodiments may include flaps or latches (e.g., at the entrance to channel 102 or chamber 101) to further fix the nerve within the chamber. The flap (not shown) may be formed of silicone to maintain the device in a closed configuration. The latch or fixation mechanism may be a latch or fixation mechanism added to the open end.

[0127] The device 100 and the signal generator may be distributed separately or arranged together as a kit.

[0128] It should be apparent that the various embodiments provide several advantages. For example, electronic devices that would otherwise be susceptible to the effects of fluid ingress and non-bio-compatible are securely separated from the aqueous in-vivo implantation environment. Further, the package 46 and / or the housing 48 are formed from materials selected for the transmission of RF energy. The silicone overmold housing 48 allows for the manufacture of complex shapes. Silicone can be processed at higher temperatures than can be tolerated by electronic components in other cases (e.g., when injection molded). In various embodiments, the device 100 has a highly reliable hermetic enclosure while having a desirable (e.g., complex) outer surface shape and durometer for engaging tissue within the body (e.g., nerve 200).

[0129] As a further example, the exemplary embodiments are easy to implant, i.e., the nerve slides into the chamber with minimal force. The exemplary embodiments also shorten the surgical time, avoid trauma, and can be implanted in a smaller space with minimal modification to the tissue compared to typical electrode cuffs. Further, the exemplary embodiments can be sutureless (i.e., do not require complex sutures to secure the nerve and are easily deployed). Further, the gentle force orientation and direction of the arm 50 promotes direct contact with the nerve, resulting in reduced power consumption, maximized stimulation, and reduced tissue ingrowth between the nerve and the electrode, reducing signal degradation, of electrical signals directly adjacent to the nerve.

[0130] Generally, the pressure for placing the largest-sized nerve in the chamber is well below 30 mmHg, which is the generally accepted acute limit for the largest-diameter nerve within the design window. In some embodiments, the nerve may have a cross-sectional dimension (e.g., diameter) of about 0.5 mm to about 3.0 mm. However, various embodiments can accommodate larger-diameter or even smaller-diameter nerves. The pressure for the holding force is also well below 20 mmHg, which is the generally accepted chronic limit for the largest-diameter nerve within the design window. To confirm this, the inventors conducted various tests. The pressure of the device on the nerve was performed on a 10-fold scale model. A pressure sensor was combined with a fluid-filled phantom nerve. The nerve was inserted into the device and removed from the device, and both the maximum pressure and the holding pressure were recorded (the insertion of the nerve was the worst-case scenario, and the clip was not manually opened, but the nerve felt the full force of the clip during insertion). The recorded maximum force was 15 mmHg, and the recorded maximum holding force was 3.1 mmHg

[0131] FIG. 14 schematically shows details of the protrusion 62 on the arm 50 according to an exemplary embodiment. As the size of the nerve varies from 100 μm to 400 μm, the angle of the protrusion 62 on the spring-loaded fixed arm can vary to accommodate a large size mismatch. Calculations for the example of 100 μm to 400 μm are shown below, which can be scaled for alternative nerve ranges. The example provided below assumes the following: The channel in the open configuration is 300 μm wide when fully open, The raised portion within the channel is slightly larger than the maximum configured size of 430 μm, The electrodes are 450 μm in the vertical and horizontal directions, The total height of the channel and the chamber is 1.4 mm. [Table 2]

[0132] Figures 15 to 17 schematically show various details of the electrode 104 according to an exemplary embodiment of the present invention. The above-described electrode 104 may have both a horizontal plane and a vertical plane to accommodate various angular engagements of the pressing portion of the arm 50 against the nerve. The surface area of the electrode 104 preferably corresponds to the required charge density of each surface of the electrode 104. Figure 15 schematically shows a curved electrode according to an exemplary embodiment of the present invention. It should be apparent that the above dimensions are merely illustrative.

[0133] Figure 15 schematically shows an angled electrode with exemplary dimensions. The angle between the two portions of the angled electrode 104 can be adjusted. A curved or folded electrode can provide better direct contact with the nerve than a conventional one-dimensional electrode. This allows for flexibility such that the angle of pressure against the nerve varies according to 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 bilateral electrodes can be configured with various interior angles, not just an "L" shape, to accommodate different electrode orientations. Figure 17 schematically shows a folded electrode 104 according to an exemplary embodiment of the present invention. The configuration of the folded electrode 104 has both sides of the electrode passing through both sides of the nerve to "pinch" the nerve between the two sides of the electrode.

[0134] Figures 18A - 20C schematically illustrate alternative embodiments of the neuromodulation device 100 according to an exemplary embodiment. Specifically, Figures 18A - 20C illustrate embodiments having a plurality of jaws 50 (e.g., formed from silicone or including a silicone overmold as described above). The body 40 is omitted in some of these figures, but it should be understood that various embodiments may include the body 40, a housing 48 (e.g., ceramic), and / or other components described above. However, in contrast to the previous embodiments described above having a channel 102 opening oriented substantially perpendicular to the body 40, Figures 18A - 20C show a channel 102 opening oriented substantially parallel to the longitudinal axis of the body 40. However, in other embodiments, the channel 102 may be oriented in any direction (e.g., oblique to the body 48). It should be understood that the orientation with respect to the body may depend on the orientation and dimensions of the body.

[0135] In some embodiments, the jaws are directly coupled to the body 40. Thus, the chamber is at least partially formed from the body 40 (e.g., by the package 46 and / or the housing surrounding the package 46). Alternatively, the jaws 50 may be separately coupled to the body by an attachment portion. For convenience, although the body 40 and the housing 48 are not shown in Figures 18A - 20C, it should be understood that various embodiments of the jaws 50 may be coupled to the housing 48 and / or the package 46.

[0136] Advantageously, a single device 100 is configured to couple to and stimulate nerves 200 of various sizes (e.g., 0.5 mm to about 4 mm).

[0137] The body 48 is shown in FIG. 18A as being smaller than the jaw portion 50, but it should be understood that the drawings are not necessarily to scale. In some embodiments, the body 48 may be larger or smaller than the jaw portion 50. Additionally, in various embodiments, the body 48 may form part of the chamber 101 having the electrode 104. However, in some other embodiments, the body 48 may not form part of the chamber 101. Instead, the jaw portion 50 and / or the intermediate portion between the jaw portions 50 may define the chamber 101.

[0138] FIGS. 18A-18C schematically illustrate the process of placing the small-diameter nerve 200 (e.g., having a diameter of about 0.5 mm to about 1.5 mm) into the chamber 101 for stimulation. The figures show a side view of the device 100.

[0139] For illustrative purposes, the nerve shown in FIGS. 18A-18C is a small-diameter nerve having a diameter of about 1 mm. The jaw portions 50 together define a V-shaped funnel 68 configured to assist a surgeon in placing the nerve 200 at the proximal end 72 of the channel 102 outside the device 100. When the nerve 200 is placed at the proximal end 72 of the channel 102, the nerve 200 preferably has a cross-sectional dimension larger than that of 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., having a dimension of about 0 mm). Advantageously, the reduction in the channel dimension 76 prevents accidental dislodgment of the nerve 200. Additionally, for that purpose, the channel 102 may have a non-linear or serpentine shape to assist in preventing accidental dislodgment of the nerve 200. However, some embodiments may include a straight channel 102.

[0140] In any case, as shown in FIG. 18B, the nerve 200 can be stretched (e.g., by a surgeon applying force) and / or crushed (e.g., by the inner surface of the channel 102) to reduce the cross-sectional dimension of the nerve 200. Preferably, the reduction in the dimension of the nerve 200 is less than 50% to prevent or reduce damage to the nerve 200 that could otherwise occur from a greater reduction in cross-sectional size. For example, a 1 mm nerve 200 may be reduced to a cross-sectional dimension of about 0.75 mm. Assuming the channel dimension 76 is about 0.5 mm, the nerve 200 may still be too large to pass through the channel 102. To that end, the device 100 may include a hinge 78 that opens the jaw 50, thereby expanding the channel dimension 76. In some embodiments, the hinge 78 is formed of a deformable material (e.g., silicone) that allows the jaw 50 to open outwardly. Additionally or alternatively, the channel 102 may include a deformable and / or elastic wall or coating that expands the channel dimension 76.

[0141] As shown in FIG. 18C, when the nerve 200 passes through the distal end 74 of the channel 102 and enters the chamber 101, the jaw 50 can close again. Due to the reduction in the channel dimension 76 and the non-linear channel 102 shape, the small-diameter nerve 200 is firmly coupled within the chamber 101. Although not drawn to scale, the jaw 50 may include a nerve contact surface 58 configured to press and / or hold the nerve 200 against the electrode 104. In various embodiments, the jaw 50 can be biased to return to the closed position and / or the deformable material is elastic and can return to its original dimensions.

[0142] FIG. 18D schematically shows a perspective view of the device 100 (with details of the chamber 101 such as the electrode 104 omitted). The channel 112 has a specific movement path 113 (also referred to as the central axis 113) for the nerve 200. For example, as shown in FIG. 18D, the central axis 113 is non-linear. The central axis 113 can be defined by the arm 50.

[0143] 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 the nerve implantation procedure, the nerve 200 is substantially parallel to the longitudinal axis 112 when moving along the central axis 113. Two different longitudinal axes 112A and 112B are shown for two different points along the central axis.

[0144] FIG. 18E schematically shows a cross-sectional view of the longitudinal axis 112A of the device of FIG. 18D. As shown, the channel 102 is axial so that the longitudinal axis 112A is continuous. This enables the nerve 200 to pass through the channel 102 with minimal manipulation by the surgeon. In some embodiments, the nerve 200 may be stretched to pass through the channel 102 and / or the channel wall formed by the jaw 50 may be deformable. FIG. 18G schematically shows a nerve passing through the channel 102 in cross-section of the axis 112A.

[0145] FIG. 18F schematically shows a cross-sectional view of the longitudinal axis 112B of the device of FIG. 18D. FIG. 18F shows a different cross-section than the view of FIG. 18D. However, again, the channel 102 is axial so that the longitudinal axis 112B is continuous. Thus, it may be said that the channel is continuously axial, i.e., the longitudinal axis 112 at any given point along the central axis 113 is continuous.

[0146] FIG. 18H schematically shows an alternative embodiment of FIGS. 18E - 18G. In particular, the longitudinal axis 112C is interrupted (e.g., by the tooth 151). In order for the nerve 200 to pass through the channel 102 of FIG. 18H, the surgeon must either perform very careful manipulation of the nerve 200 (e.g., to conform to the shape of the axis 112C), push the nerve through by applying traumatic pressure, or actively open the jaw 50 (e.g., using a separate instrument). FIG. 18H does not have an axial longitudinal axis 112C at rest (as shown in the figure), but when the jaw 50 is opened, the longitudinal axis 112C can become axial. However, the exemplary embodiments advantageously have axial longitudinal axes 112A, 112B at rest so that the nerve can slide easily within the chamber 101.

[0147] Accordingly, some embodiments have a non - linear channel 102 that is continuously axial (i.e., along the central axis 113), as shown in FIGS. 18D - 18F. Advantageously, the nerve can pass through the channel 102 with minimal manipulation and non - traumatic forces, without the need for a separate instrument to open the arm 50.

[0148] FIGS. 19A - 19C schematically show the process of placing the mid - diameter nerve 200 (e.g., about 1.5 mm to about 2.5 mm in diameter) within the chamber 101 for stimulation. The figures show a side view of the device 100.

[0149] For illustration purposes, the nerve 200 shown in FIGS. 19A-19C is a medium-sized nerve with a diameter of approximately 2 mm. Similar to the process described above, the V-shaped funnel assists in positioning the nerve 200 relative to the proximal end 72 of the channel 102. For illustration purposes, the nerve 200 can be stretched to reduce the diameter of the nerve to approximately 1.5 mm. As described above, the channel dimension 72 can be approximately 0.5 mm. Thus, when the jaw 50 is in the rest position, the nerve is considerably thicker than the channel 102 is wide. The jaw 50 can be expanded and opened to increase the channel dimension 76 and allow the nerve 200 to pass through the channel. To that end, an exemplary embodiment can include a delivery device having a cam mechanism that pushes the jaw 50 open via a deformation and / or a hinge connection. FIG. 18B schematically shows a hinge that opens in two parts, although various embodiments do not have a hinge opening (otherwise there is a possibility of confining a larger deformed portion of the nerve).

[0150] As shown in FIG. 19C, the nerve 200 is stationary within the chamber 101 and the jaw 50 can be closed again. For example, the nerve 200 relaxes and returns to its 2 mm diameter. Additionally, the silicone of the jaw 50 can relax, the channel dimension 76 returns to approximately 0.5 mm, preventing the nerve from retreating out of the channel 102. In some embodiments, the jaw 50 is biased to a rest position (e.g., a position where the channel 102 has a dimension 76 of approximately 0.5 mm or to a fully closed position). Additionally or alternatively, the delivery device can close the jaw 50. The silicone deformation and the small Z-channel 102 result in a medium-sized nerve being firmly coupled within the chamber 101.

[0151] Figures 20A - 20C schematically illustrate the process of placing the large - diameter nerve 200 (e.g., about 2.5 mm to about 3.5 mm in diameter) into the chamber 101 for stimulation. The figures show a side view of the device 100. As shown in FIG. 20A, the device 100 is either stationary or considered to be in a rest position. In the rest position, the device is in a steady state, i.e., no force is applied to the device to open the jaw 50 (e.g., by either a nerve or an instrument). Thus, in various embodiments, the rest position is the "closed position" of the device. As described above, 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 at rest. Further, the channel 112 can be continuously axial when the device is stationary (and when the device is transitioning to its open configuration). Some embodiments can close the channel (e.g., using a flexible flap or valve having a very low cracking pressure). Such closing can be applied along the channel 102 without limiting the ability to use the slide - and - lock nerve placement method.

[0152] For illustration purposes, the nerve 200 shown in FIGS. 20A - 20C is described as a large - diameter nerve with a diameter of about 3 mm when not deformed. The nerve 200 can be placed at the proximal end 72 of the channel as described above. The device 100 can have a chamber dimension 83A (e.g., maximum chamber dimension or minimum chamber dimension, etc.) without the nerve 200 therein.

[0153] As shown in FIG. 20B, the nerve 200 can move along the central axis 113 of the channel. In some embodiments, the nerve 200 can be stretched (e.g., by a surgeon) and / or crushed (e.g., by the inner surface of the channel 102) to reduce the cross-sectional dimensions of the nerve 200. Preferably, the reduction in the dimensions of the nerve 200 is less than 50% to ensure the safety of the nerve 200, as otherwise some damage could occur from a greater reduction in cross-sectional size. For example, the nerve may be reduced to a cross-sectional dimension of about 2.25 mm. Assuming the channel dimension 76 is about 0.5 mm, the nerve 200 may still be too large to pass through the channel 102. For this purpose, the hinge 78 opens the jaw 50 and expands the channel 102 dimension 76 to allow the large-diameter nerve 200 to pass through the channel 102. Thus, various embodiments have a chamber 101 of adjustable size and / or shape. Similarly, the chamber dimension 83B can be adjusted by the movement of one or more arms 50.

[0154] As shown in FIG. 20C, when the nerve 200 passes through the distal end 74 of the channel 102 and enters the chamber 101, the jaw 50 can close again. However, due to the large size of the nerve 200, the jaw 50 may or may not be able to close completely to return the channel 102 to its original dimension 77. Similarly, the arm 50 may or may not be able to close completely to return the chamber 101 to its original dimension 83A. When the nerve 200 is disposed within the chamber 101, the chamber 101 may have a new adjusted chamber dimension 83C. In any case, the jaw 50 holds the large-diameter nerve 200 within the chamber 101. To that end, the jaw 50 may include a relaxation space 64 (also referred to as a deformation region 64) that can deform and expand when the shape of the nerve 200 is compressed (e.g., so that the cross-sectional area of the nerve does not shrink as much as it would if there were no deformation region 64). In various embodiments, the nerve 200 can deform and / or expand in one or more relaxation spaces 64 to reduce the pressure applied to the nerve. The device can be configured such that a pressure of less than 4 kPa that occupies the nerve relaxation space 64 is applied to the nerve. Additionally, to assist in reducing the pressure applied to the nerve 200, the contact surface 58 may be configured to deform, thereby providing additional space for the nerve 200 to expand within the chamber 101. Further, in some embodiments, as shown in FIG. 20C, the channel 102 dimension 76 can be expanded in a stationary configuration due to interference with the large-diameter nerve 200.

[0155] Due to the reduction of the channel dimension 76 and the non-linear channel 102 shape, the small-diameter nerve 200 is firmly coupled within the chamber 101. Although not drawn to scale, the jaw 50 may include a nerve contact surface 58 configured to press and / or hold the nerve 200 against the electrode 104.

[0156] It should be understood that various embodiments advantageously enable the nerve 200 to expand / deform within the chamber 101, as opposed to compensatory expansion / deformation that would otherwise occur outside the chamber 101 and potentially damage the nerve 200. However, in various embodiments, some deformation may occur outside the chamber 101. Preferred embodiments advantageously provide a jaw having a deformable nerve contact portion, as well as a designated relaxation space 64 within the device that allows for adjacent / localized deformation to the compression region on the nerve. As is known in the art, a nerve is composed of a bundle of axons. By allowing for local deformation of the nerve, the position of individual axons and / or fascicles of fibers can be repositioned without necessarily damaging the individual axons as can occur when the nerve is strongly compressed or stretched.

[0157] Figures 21 and 22 schematically illustrate a nerve modulation device 100 according to an exemplary embodiment. FIG. 21 shows four different views of the nerve modulation device 100. The hermetic body 40 is mostly omitted. However, a through-conductor 80 extending from within the hermetic body 40 is shown. The through-conductor 80 extends through the package 46 and the buffer layer 49. The through-conductor 80 then forms an electrode 104 within a chamber 101 defined by the movable arm 50.

[0158] The movable arm 50 is shown biased toward a closed position. Although referred to as a "closed position", some embodiments may have a gap 76. Thus, it is not necessary for the movable arm 50 to completely close the gap 76 at the closed position. The closed position 76 is used to refer to the position of the channel 102 when the channel is narrow for holding a nerve. When 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 flexion points 81 formed from a material configured to flex to accommodate the nerve 200. It should be understood that the gap 76 need not be completely closed to be biased toward the closed position. Similarly, the gap 76 need not be completely open to transition toward the open position.

[0159] As described above (e.g., with reference to FIGS. 18A-18G), the device 100 defines an axial channel along the length of the channel 102. Advantageously, a continuously axial channel 112 that can facilitate insertion and / or removal of the nerve 200, using, for example, the slide-and-lock method described in U.S. Patent Application No. 16 / 414,169, which is hereby incorporated by reference in its entirety. 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. 18H having interlocking teeth). However, embodiments having an axial channel 112 can advantageously use the slide-and-lock method, for example, by axially extending the nerve 200 and sliding it continuously through the axial channel 102. This method advantageously does not require the use of an external instrument to help open the jaw 50 for the nerve to cross the channel 102 or other forces (other than the pressure of the nerve pressing on the jaw 50).

[0160] FIG. 22 shows four different views of an alternative of the movable arm 50 according to an exemplary embodiment. FIG. 22 shows a bending mechanism 81 configured to move relative to larger diameter nerves when the larger diameter nerves pass through the channel 102 and / or when they fit within the chamber 101. However, the bending mechanism 81 (e.g., the neck portion) assists in keeping the smaller diameter nerves pressed against the electrodes 104. Advantageously, the neck portion 81 allows the head portion 82 to pivot so as to accommodate nerves 200 of various sizes within the channel 102 and / or the chamber 101.

[0161] In some embodiments, the through conductor 80 is welded to a separate electrode 104 at a weld point outside the hermetic package 46. However, various embodiments provide non-jointed (e.g., non-welded) electrodes 104 formed by the through conductor 80. The tolerances for welding the electrodes 104 onto the through pins 80 at this scale are difficult. By using non-jointed electrodes 104, manufacturing problems are simplified. Further, as shown, a portion of the electrode 104 may be embedded within the arm 50. Thus, the electrode 104 may 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 perimeter length of the nerve 200 disposed within the chamber 101. In some embodiments, the exposed electrode 104A is configured to contact at least 40% of the perimeter length of the nerve 200 disposed within the chamber 101.

[0162] As shown, various embodiments combine a neural coupling portion (i.e., chamber 101) and an implantable pulse generator (e.g., within package 46) to advantageously provide a smaller device 100 and a simpler implantation technique. Additionally, various embodiments do not require an external lead wire between the neural coupling portion and the IPG. Advantageously, a single unbonded through-conductor 81 can extend from the hermetic housing 46 into the chamber 100 to form the electrode 104. This is in contrast to devices where the through-conductor 81 is welded to the electrode 104. Exemplary embodiments can directly use the through-conductor as the electrode 104, thereby providing an unbonded or continuous electrode.

[0163] Prior art devices implant the IPG by exposing the nerve and placing a cuff, then tunneling a lead wire using a customized instrument at the location of the IPG where a subcutaneous pocket has been formed for placing the IPG. The IPG is then connected to the lead wire and placed in the pocket. In contrast, exemplary embodiments provide a simpler technique because sizing is automatic with respect to the nerve (within an acceptable range of about + / - 50% to 75% for a 2 mm nerve in the range of 0.5 - 3.5 mm). Advantageously, tunneling is not performed and there is no need for a separate surgical location for the IPG.

[0164] Furthermore, the entire lead wire body is not required along with connector blocks, proximal connectors, and other similar components. The through-conductor 81 (e.g., extending from the hermetic package 46) can be used as the electrode 104. The through-conductor 81 may be formed of, for example, a Pt-Ir material. A further advantage of using this structure as the electrode 104 is that the through-pin 81 can be bent to non-invasively couple the nerve 200 and utilized to support the structure and holding force of the movable arm 50.

[0165] Accordingly, an exemplary embodiment provides a neuromodulation device in which the through conductor 81 operates as both an electrode 104 incorporated to achieve appropriate flexure characteristics of the arm 50 and a structural component. The material properties are selected such that the nerve 200 has intimate but non-invasive contact with the electrode 104.

[0166] The movable and / or flexible arm 50 can be adjusted both during insertion in the nerve channel 102 and when the nerve is disposed within the chamber 101. The arm 50 is configured to adjust the dimensions of the chamber 101 to capture smaller diameter nerves (e.g., 0.5 mm, 1 mm) without applying traumatic pressure to larger diameter nerves 200 (e.g., 3 mm, 4 mm).

[0167] Exemplary embodiments are configured to hold a nerve having a size of 0.5 mm to 4 mm within chamber 101 at a pressure of less than 6.7 kPa. Nerve 200 is relatively susceptible to damage by high pressure. Thus, exemplary embodiments form arm 50 from a material that biases the arm to reduce the pressure on the nerve when the nerve 200 passes through channel 102 and when the nerve is stationary within chamber 101. In particular, arm 50 is configured to apply less than 6.7 kPa to nerve 200 to prevent structural damage to the nerve. For example, channel 102 preferably has a cracking pressure of less than 6.7 kPa. In various embodiments, device 100 is configured such that a pressure of less than 10 kPa or less than about 1.5 psi is applied to the nerve. Of course, some embodiments may provide higher pressures than those disclosed herein. This pressure can be reduced depending on the amount of time nerve 200 is within channel 102. For example, if it takes more than 2 minutes to pass the nerve through channel 102, device 100 should be configured such that a pressure of less than 6.7 kPa is applied to the nerve. Similarly, nerve 200 is located within the chamber for an extended period of time, and thus the device can be configured such that a pressure of less than 4 kPa is applied to the nerve at any given time within the chamber. Device 100 can be configured to provide these pressures, among other things, using certain materials, relaxation space 64, and / or a plurality of arms 50.

[0168] Furthermore, exemplary embodiments are configured to hold a nerve having a size of 0.5 mm to 4 mm within chamber 101 at a pressure of less than 4 kPa (or 30 mmHg) to reduce undesirable long-term effects such as nerve function blockage and / or edema. Thus, chamber 101 preferably has a holding pressure of less than 4 kPa for nerve 200 having a diameter of 1 mm to 3 mm (nerve diameter is the generally accepted size measurement of the nerve when the nerve is stationary and not deformed).

[0169] The bench test of the device 100 shows that the maximum insertion force for a large-diameter nerve (e.g., 4 mm in diameter) is less than 2 kPa (15 mmHg). After the model nerve is stationary in the chamber, the compression is 0.147 kPa (1.1 mmHg) on average, indicating that the flexible channel / chamber approach is a feasible approach.

[0170] In addition, some electrodes implanted in the nerve in clinical studies chronically compress them (about 40%). These are called "FLAT" electrodes (mainly FINE electrodes), and it has been reported that an estimated intraneural pressure of less than 30 mmHg can re-form the nerve without significant changes in neurophysiology or tissue structure. Flattening the nerve by more than 60% results in a pressure of 60 mmHg, which may cause nerve damage. The initial bench tests of NeuroClip showed that, as described in the previous paragraph, chronic compression values much lower than the 60 mmHg shown with "flat" electrodes can be achieved.

[0171] Exemplary embodiments provide a neuromodulation device configured to non-invasively couple to various nerve sizes from 0.5 mm to 4 mm. As described herein, non-invasive coupling applies a continuous pressure of less than 4 kPa to the nerve when the nerve is in the chamber (e.g., for hours or days). Further, non-invasive coupling provides less than 6.7 kPa when passing through the channel 102 (e.g., passing through the channel for a short time of less than 1 minute).

[0172] The device 100 is configured to accommodate various nerve sizes (e.g., from 1 mm to 3 mm). The same approach can be scaled to multiple nerve size ranges.

[0173] To accommodate various nerve sizes, the device is flexible enough to allow the largest diameter nerve to pass through the channel portion and rest within the chamber, yet not so large that the smallest diameter nerve can easily slip through while maintaining contact with the electrode. To that end, various embodiments use Nusil (products made by NUSIL with Class VI biocompatibility approval), a biomaterial that is widely used with long-term active implantable devices. This material accommodates the largest diameter nerve passing through channel 102 and flexes to reform within the additional space provided to prevent the build-up of pressure inside the nerve when the nerve is contained within the chamber. Instead of the large round nerve being overly compressed within the chamber, the shape of the nerve changes to fill the provided open space. Nerve 200 can withstand a moderate reformation of its cross-sectional shape (e.g., a 30% reduction in maximum cross-sectional area) without causing damage.

[0174] Figures 23A - 23C schematically illustrate a nerve modulation device according to an exemplary embodiment. Figure 23A shows a 1 mm nerve pressing against arm 50 and projection 54. In some embodiments, arm 50 may be movable and flex in response to pressure from the nerve. Additionally or alternatively, arm 50 and / or projection 54 may be 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 stationary. Figure 23B shows a nerve deforming to pass continuously through the axially oriented channel 102. Finally, Figure 23C shows the position of nerve 200 relative to electrode 104. Unlike the stationary arm 50, an exemplary embodiment with a movable arm 50 can provide a contact pressure that presses nerve 200 into contact with electrode 104.

[0175] The nerves shown in FIG. 23C are relatively small-diameter nerves (e.g., 1 mm in diameter). Larger-diameter nerves (e.g., 3 mm or more) deform to fit into the available space within chamber 101 without applying traumatic pressure along the nerve after reshaping. FIGS. 23D and 23E schematically show larger-diameter nerves that change their cross-sectional shape while maintaining their cross-sectional area.

[0176] In addition, the small-diameter nerve 200 is held within the chamber in very close proximity to the electrode 104, allowing the stimulation amplitude to remain low and signal efficiency to be maintained. Tests by the inventors using a device having one movable arm 50 for larger-diameter nerves (e.g., 3 mm or more) showed pressures of less than 5 mmHg after fitting within the chamber.

[0177] Exemplary embodiments should clearly provide the advantage of a single device that can reliably stimulate when coupled to nerves of various different sizes. Further, the device can reliably hold nerves of various sizes (e.g., from a small diameter of 0.5 mm to a large diameter of 4 mm) without overcompressing / traumatizing the nerve 200. Indeed, the chamber 101 (e.g., a portion of the movable arm 50) is adjusted to assist in holding the nerve.

[0178] Various embodiments use a combination of epoxy and medium durometer silicone (e.g., Shore A value of 60 - 90), with or without additional structural elements. For example, the epoxy can be used to support through conductors and minimize bending stress points. Through conductors (e.g., Pt - Ir, gold, nitinol or similar materials) are bent and incorporated into the header structure to provide additional structural support and holding force. Subsequently, through electrodes or attached electrodes are embedded in a low - to - medium durometer silicone portion (typically 30 - 50 Shore A) that has the flexibility to achieve the placement and resistance necessary to hold the nerve in place without traumatizing the nerve. This structure, unlike a typical nerve cuff, requires that in extreme cases both the nerve and the cuff deform to "slide" the nerve through the channel into the chamber. By taking advantage of the natural ability of the nerve to stretch and the slight movement of the silicone or wire arms of the device, acute nerve pressure is minimized, even for nerves up to 50 - 75% larger in diameter. Additionally, by taking advantage of the ability of the largest diameter nerves to adjust and redistribute their structure with minimal static or final force to minimize internal nerve pressure, there is sufficient space within the chamber to achieve adequate static pressure under the 60% compression that is known to cause nerves to relax and become damaged.

[0179] For the smallest diameter nerves, the "arm" portion of the device does not deform as much to achieve the same movement through the channel. Inside the chamber, significant deformation is required, but the through - flexure wire structure as an electrode provides sufficient opportunity to maintain a close connection between the nerve and the electrode, minimizing the impact on signal strength.

[0180] Thus, in various embodiments, channel 102 and / or chamber 101 can be formed of a material configured to deform in response to non - traumatic pressure from the nerve (e.g., less than 6.7 kPa). Additionally, channel 102 and / or chamber 101 are configured to change their dimensions as a result of one or more movable arms 50.

[0181] Among the advantages, and in particular in the exemplary embodiments, the continuously axially extending channel 102 provides for easy placement of the nerve into the chamber and removal of the nerve from the chamber 101. The channel 102 may also be non-linear in order to assist in retaining the nerve within the channel (such that the nerve does not easily slip out of the continuously axially extending channel). The continuously axially extending channel 102 also assists in reducing trauma to the nerve 200 during the placement and removal procedures. To further assist in reducing trauma, the device may include one or more flexure points 81 configured to bend or pivot to accommodate nerves of various shapes and sizes. These features cooperate to enable the nerve to slide through the channel and / or push and / or deform the arm 50 to allow passage of the nerve.

[0182] In various embodiments, it should be apparent that one or more arms 50 define the size of the chamber 101 and / or the channel 102. The arm 50 further provides a non-invasive force that biases nerves 200 of various sizes towards the electrode 104 such that the electrode contacts at least 20%, at least 25%, or at least 35% of the circumferential length of the nerve 200. In various embodiments, particularly for larger diameter nerves (e.g., 3 mm or greater), the electrode 104 contacts at least 60% of the circumferential length of the nerve when the nerve 200 is within the chamber 101. Thus, the device 100 advantageously accommodates non-invasively nerves of a variety of different sizes. Further, one or more arms 50 assist in maintaining continuous contact and electrical coupling with the electrode 104 by providing a constraining force that compresses the nerve. Additionally, the exemplary embodiments couple the device to the nerve without using sutures and without requiring special instruments that would facilitate easy removal of the device.

[0183] Various embodiments describe devices for coupling to and treating nerves having a diameter of from about 0.5 mm to about 4 mm, but it should be understood that such devices and methods can be extended to accommodate nerves of a variety of different sizes. For example, one of ordinary skill in the art may use the disclosure herein to configure a device to couple to a larger diameter nerve having a diameter of from about 5 mm to about 8 mm. In another example, the device may be configured to couple to a nerve 200 having a diameter of from about 0.2 mm to about 2 mm. These devices can be configured to couple to various nerve sizes without damaging the nerve (e.g., by applying a pressure of less than 4 kPa to the nerve).

[0184] Various embodiments of the invention have been described and illustrated herein, but one of ordinary skill in the art will readily envision various other means and / or structures for performing the functions and / or obtaining the results and / or one or more of the advantages described herein, and each such variation and / or modification is to be regarded as within the scope of the embodiments of the invention described herein. More generally, one of ordinary skill in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are intended to be exemplary, and that the actual parameters, dimensions, materials, and / or configurations will depend upon one or more specific applications in which the teachings of the invention are used. One of ordinary skill in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Accordingly, the foregoing embodiments are presented by way of example only, and it should be understood that embodiments of the invention may be practiced otherwise than as specifically described and claimed within the scope of the appended claims and their equivalents. Embodiments of the invention disclosed herein are directed to each individual feature, system, article, material, kit, and / or method described herein. In addition, any combination of two or more such features, systems, articles, materials, kits, and / or methods is included within the scope of the invention disclosed herein if such features, systems, articles, materials, kits, and / or methods do not mutually conflict.

[0185] The concepts of various inventions may be embodied in one or more ways, and examples thereof are provided. The operations performed as part of a method may be ordered in any suitable way. Thus, even if an exemplary embodiment shows operations as sequential, embodiments may be constructed in which the operations are performed in a different order than the example, including performing some operations simultaneously.

[0186] The subject matter included in this specification is described in detail for purposes of illustration, but such details are for that purpose only, and the present disclosure is not limited to the disclosed embodiments. On the contrary, it is intended to cover modifications and other configurations 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 can be combined with one or more features of any other embodiment.

[0187] Other examples are within the scope and spirit of the description and the appended claims. Additionally, the specific functions described above can be implemented using software, hardware, firmware, wiring, or any combination thereof. The features implementing the functions can also be physically arranged in various locations, including being distributed such that parts of the function are implemented in different physical locations.

[0188] The subject matter included in this specification is described in detail for purposes of illustration, but such details are for that purpose only, and the present disclosure is not limited to the disclosed embodiments. On the contrary, it is intended to cover modifications and equivalent configurations 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 can be combined with one or more features of any other embodiment.

[0189] Other examples are within the scope and spirit of the description and the claims. Additionally, the specific functions described above can be implemented using software, hardware, firmware, wiring, or any combination thereof. The features implementing the functions can also be physically located in various positions, including being distributed such that portions of the functions are implemented in different physical locations.

Claims

1. A main body comprising a sealed housing for containing electronic equipment and a buffer layer that at least partially encloses the sealed housing, A movable arm connected to the main body, configured to transition between an open configuration and a closed configuration, and biased toward the closed configuration, A nerve stimulation chamber, at least partially defined by the movable arm, configured to hold a nerve therein, wherein the size and shape of the chamber are adjustable by the movement of the arm in response to contact with the nerve, An open channel through which the nerve passes and moves, wherein the channel is at least partially defined by the movable arm, the size and shape of the channel are adjustable by the movement of the arm in response to contact with the nerve, and the channel is continuously axial along the longitudinal axis of the channel when the movable arm is in the closed configuration. The electrodes in the chamber and A neural control system that includes this.

2. The nerve conditioning device according to claim 1, further comprising a second movable arm configured to transition between an open configuration and a closed configuration, the second movable arm being biased toward the closed configuration, and the movement of the second movable arm adjusting the size of the chamber and / or the channel.

3. The nerve conditioning device according to claim 1, wherein the movable arm is configured to non-traumatically hold the nerve having a maximum static cross-sectional dimension of 0.5 mm to 4 mm within the chamber when the movable arm is biased toward the closing configuration.

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

5. The nerve conditioning device according to claim 1, wherein the movable arm includes one or more bending points.

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

7. The nerve conditioning device according to claim 1, wherein a continuous through-conductor wire extending through the sealed housing forms the electrode.

8. The neural control device according to claim 7, wherein the channel is nonlinear.

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

10. The nerve modulator according to claim 1, wherein the channel is nonlinear and continuously axial.

11. A method of stimulating nerves, A main body comprising a sealed housing for containing electronic equipment and a buffer layer that at least partially encloses the sealed housing, A movable arm connected to the main body, configured to transition between an open configuration and a closed configuration, and biased toward the closed configuration, A nerve stimulation chamber, at least partially defined by the movable arm, configured to hold a nerve within it, wherein the size and shape of the chamber are adjustable by the movement of the arm, A channel through which the nerve passes and moves, wherein the channel is at least partially defined by the movable arm, the size and shape of the channel are adjustable by the movement of the arm, and the channel is continuously axial along its longitudinal axis, The electrodes in the chamber and To provide a neural control device having, The nerve is moved through the channel, and the contact between the nerve and the movable arm causes the movable arm to move from the closed configuration to the open configuration, thereby expanding the channel. The nerves are placed inside the chamber. Methods that include...

12. Transmitting a regulatory signal to the nerve via the electrode, The regulatory signal is configured to activate the pelvic floor in a predetermined manner in order to reduce the influence of symptom signals on the spinal cord. The method according to claim 11, further comprising:

13. The method according to claim 11, wherein the nerve is placed in the chamber, and the nerve is brought into contact with the electrode.

14. The method according to claim 11, wherein the movable arm is positioned in the closed configuration to compress the nerve in the chamber such that the cross-sectional shape of the nerve changes without damaging the nerve.

15. The method according to claim 11, wherein the housing includes a projection configured to press against the movable arm in the closed configuration, the projection being configured to limit the amount of compression on the nerve from the movable arm.

16. The method according to claim 11, wherein a continuous through conductor extending through the sealed housing forms the electrode.

17. The method according to claim 11, wherein the electrode is in contact with more than 50% of the circumference of the nerve.

18. The method according to claim 11, wherein the movable arm is biased toward the closing configuration.

19. The method according to claim 11, wherein the nerve includes the perineal nerve.

20. The method according to claim 12, wherein transmitting comprises generating an adjustment signal using a signal generator and transmitting it using the electrodes, wherein the adjustment signal is transmitted using one or more wired or wireless communication media.

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