WO2020198453A1

WO2020198453A1 - Ileus prevention device

Info

Publication number: WO2020198453A1
Application number: PCT/US2020/024922
Authority: WO
Inventors: Vivek SANT; Kristin BRUNE; Adrian TROMEL
Original assignee: Texas Medical Center
Current assignee: Texas Medical Center
Priority date: 2019-03-27
Filing date: 2020-03-26
Publication date: 2020-10-01
Anticipated expiration: 2021-09-27

Abstract

Disclosed herein are devices, systems, and methods for preventing and treating ileus in an individual in need thereof. Also described herein are methods for modulating the vagus nerve utilizing the described devices and systems. In some embodiments, the device includes a housing configured to anchor the device on or near the ear of an individual, an attachment having one or more electrodes configured to stimulate an auricular branch of the vagus nerve and a conductive material configured to contact the cymba concha, a power source configured to provide at most 8 hours of electrical stimulation, an electrical circuit configured with a fixed setting for the electrical stimulation, an activation mechanism configured to activate the electrical stimulation, and a stimulation status indicator. In some embodiments the device is configured to selectively stimulate one or more fiber types of the vagus nerve.

Description

ILEUS PREVENTION DEVICE

CROSS-REFERENCE

[0001] This application claims the benefit of U.S. Provisional Application No. 62/824,886, filed March 27, 2019, entitled“Ileus Prevention Device”; and U.S. Provisional Application No.

62/928,827, filed October 31, 2019, entitled“Ileus Prevention Device”; which applications are incorporated herein by reference.

BACKGROUND

[0002] Ileus is the disruption of peristaltic ability of the gastrointestinal tract that often follows abdominal surgery. Ileus is multifactorial in etiology and can encompass or be alternatively described as post-operative ileus, paralytic ileus, physiological ileus, or ileus. Patients with ileus may vomit and develop abdominal distention and need to stay in the hospital for several extra days until they recover. Thus, there remains a need to prevent and treat ileus.

SUMMARY

[0003] Disclosed herein, in certain embodiments, are systems, devices, and methods for preventing and treating ileus in an individual in need thereof. In certain embodiments, also described herein are methods for modulating the vagus nerve utilizing the described devices, systems, and methods.

[0004] Described herein is a device for modulating a vagus nerve in an individual in need thereof, the device comprising: (a) a housing, wherein the housing is configured to anchor the device on or near an external ear of the individual; (b) an attachment coupled to the housing, the attachment comprising: (i) one or more electrodes, wherein the one or more electrodes are configured to deliver an electrical stimulation to an auricular branch of the vagus nerve, and (ii) a conductive material located at a skin-side surface of the attachment, wherein the attachment is configured to contact a skin of a cymba concha of the external ear with the conductive material when the housing is anchored; (c) a power source disposed within the housing, wherein the power source is configured to provide at most 8 hours of the electrical stimulation; (d) an electrical circuit disposed within the housing, coupled to the one or more electrodes, and configured with a fixed setting for the electrical stimulation; (e) a mechanism of activation coupled to the housing and operably coupled to the power source and the electrical circuit, wherein the mechanism of activation is configured to activate the electrical stimulation; and (f) a stimulation status indicator coupled to the housing, wherein the stimulation status indicator indicates an on status, a progress of the electrical stimulation, or both. In some embodiments, the housing is configured to fit in and maintain its position in a concha cavum of the individual, thereby anchoring the device in the external ear of the individual. In some embodiments, the housing comprises a pliable material configured to conform to the concha cavum when inserted therein. In some embodiments, the housing is configured to maintain a position behind the external ear, thereby anchoring the device near the external ear of the individual. In some embodiments, the housing and the attachment are connected to one another by an over-the-ear hook component. In some embodiments, the housing comprises an earplug configured to fit in an ear canal of the individual. In some embodiments, the earplug is configured to fit in an external portion of the individual’s ear canal. In some embodiments, the earplug comprises a pliable material that conforms to the ear canal when inserted therein. In some embodiments, the earplug is flanged. In some embodiments, the housing is shaped as an ergonomic handle and configured to set or manipulate an initial position of the device within the external ear. In some

embodiments, the housing comprises an attached clip that is configured to anchor the device over the external ear. In some embodiments, the stimulation status indicator is disposed on a side of the housing or on a surface of the housing that is opposite to the skin-side surface. In some embodiments, the housing further comprises a post. In some embodiments, the post and the attachment are connected to the housing on opposite sides of the housing. In some embodiments, the electrical circuit, the power source, the power button, the stimulation status indicator, or a combination thereof is disposed on or within the post. In some embodiments, the post is shaped as an ergonomic handle and configured to set or manipulate an initial position of the device within the external ear. In some embodiments, the attachment is configured to maintain the contact between the conductive material and the skin in the individual’s cymba concha when the device is anchored on or near the external ear of the individual. In some embodiments, the attachment is semi-flexible. In some embodiments, the attachment has a curved shape. In some embodiments, the attachment is curved toward a cheek of the individual. In some embodiments, the attachment has a straight shape. In some embodiments, the attachment comprises a pliable material configured to conform to the ear when inserted therein. In some embodiments, the one or more electrodes comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20 or more electrodes disposed on or within the attachment. In some embodiments, at least one of the one or more electrodes has a shape of a loop, a cross, a bar, a dot, or a wire. In some embodiments, at least one of the one or more electrodes is a bar-shaped electrode. In some embodiments, at least one of the one or more electrodes is a dot-shaped electrode. In some embodiments, the attachment comprises a non- conductive material disposed on a surface of attachment that is opposite to the skin-side surface of the attachment. In some embodiments, the conductive material is placed between the skin and the one or more electrodes. In some embodiments, the conductive material at least partially covers the one or more electrodes on the skin-side surface. In some embodiments, the attachment is an electrode. In some embodiments, the attachment consists essentially of the conductive material. In some embodiments, the attachment is made of the conductive material. In some embodiments, the conductive material comprises a conductive gel, a conductive polymer, a conductive liquid selected from water, ionic liquid and alcohol, metal, an alloy, carbon black, or a combination thereof. In some embodiments, the conductive material comprises a hydrogel. In some embodiments, the conductive material comprises a conductive silicone. In some

embodiments, the fixed setting sets the electrical stimulation at a frequency of at least 0.1 Hz, at least 1 Hz, at least 2 Hz, at least 3 Hz, at least 4 Hz, at least 5 Hz, at least 6 Hz, at least 7 Hz, at least 8 Hz, at least 9 Hz, at least 10 Hz, at least 11 Hz, at least 12 Hz, at least 13 Hz, at least 14 Hz, at least 15 Hz, at least 16 Hz, at least 17 Hz, at least 18 Hz, at least 19 Hz, at least 20 Hz, at least 21 Hz, at least 22 Hz, at least 23 Hz, at least 24 Hz, at least 25 Hz, at least 26 Hz, at least 27 Hz, at least 28 Hz, at least 29 Hz, at least 30 Hz, at least 40 Hz, or at least 50 Hz. In some embodiments, the fixed setting sets the electrical stimulation at a frequency of at most 5 Hz, at most 6 Hz, at most 7 Hz, at most 8 Hz, at most 9 Hz, at most 10 Hz, at most 11 Hz, at most 12 Hz, at most 13 Hz, at most 14 Hz, at most 15 Hz, at most 16 Hz, at most 17 Hz, at most 18 Hz, at most 19 Hz, at most 20 Hz, at most 21 Hz, at most 22 Hz, at most 23 Hz, at most 24 Hz, at most 25 Hz, at most 26 Hz, at most 27 Hz, at most 28 Hz, at most 29 Hz, at most 30 Hz, at most 35 Hz, at most 40 Hz, at most 45 Hz, at most 50 Hz, at most 60 Hz, at most 70 Hz, at most 80 Hz, at most 90 Hz, or at most 100 Hz. In some embodiments, the fixed setting sets the electrical stimulation at a frequency of from about 5 Hz to about 60 Hz. In some embodiments, the fixed setting sets the electrical stimulation at a frequency of about 25 Hz. In some embodiments, the fixed setting comprises a plurality of frequencies of from 0.1 Hz to 100 Hz for the electrical stimulation. In some embodiments, the fixed setting comprises a frequency of about 0.1 Hz, about 1 Hz, about 2 Hz, about 3 Hz, about 4 Hz, about 5 Hz, about 6 Hz, about 7 Hz, about 8 Hz, about 9 Hz, about 10 Hz, about 11 Hz, about 12 Hz, about 13 Hz, about 14 Hz, about 15 Hz, about 16 Hz, about 17 Hz, about 18 Hz, about 19 Hz, about 20 Hz, about 21 Hz, about 22 Hz, about 23 Hz, about 24 Hz, about 25 Hz, about 26 Hz, about 27 Hz, about 28 Hz, about 29 Hz, about 30 Hz, about 35 Hz, about 40 Hz, about 45 Hz, about 50 Hz, about 60 Hz, about 70 Hz, about 80 Hz, about 90 Hz, or about 100 Hz for the electrical stimulation. In some embodiments, the fixed setting sets the electrical stimulation at a pulse width of at least 1 ps, at least 10 ps, at least 50 ps, at least 100 ps, at least 150 ps, at least 200 ps, at least 250 ps, at least 300 ps, at least 350 ps, at least 400 ps, at least 450 ps, or at least 500 ps. In some embodiments, the fixed setting sets the electrical stimulation at a pulse width of at most 100 ps, at most 150 ps, at most 200 ps, at most 250 ps, at most 300 ps, at most 350 ps, at most 400 ps, at most 500 ps, at most 600 ps, at most 700 ps, at most 800 ps, at most 900 ps, at most 1000 ps, at most 1500 ps, or at most 2000 ps. In some embodiments, the fixed setting sets the electrical stimulation at a pulse width of from about 100 ps to about 2000 ps. In some embodiments, the fixed setting sets the electrical stimulation at a pulse width of about 250 ps. In some embodiments, the fixed setting comprises a plurality of pulse widths of from 1 ps to 2000 ps for the electrical stimulation. In some embodiments, the fixed setting comprises a pulse width of about 1 ps, about 10 ps, about 50 ps, about 100 ps, about 150 ps, about 200 ps, about 210 ps, about 220 ps, about 230 ps, about 240 ps, about 250 ps, about 260 ps, about 270 ps, about 280 ps, about 290 ps, about 300 ps, about 350 ps, about 400 ps, about 450 ps, about 500 ps, about 600 ps, about 700 ps, about 800 ps, about 900 ps, or about 1000 ps for the electrical stimulation. In some embodiments, the fixed setting sets the electrical stimulation at a current passing through one of the one or more electrodes of at least 0.01 mA, at least 0.1 mA, at least 1 mA, at least 2 mA, at least 3 mA, at least 4 mA, at least 5 mA, at least 6 mA, at least 7 mA, at least 8 mA, at least 9 mA, at least 10 mA, at least 11 mA, at least 12 mA, at least 13 mA, at least 14 mA, at least 15 mA, at least 16 mA, at least 17 mA, at least 18 mA, at least 19 mA, at least 20 mA, at least 21 mA, at least 22 mA, at least 23 mA, at least 24 mA, at least 25 mA, at least 26 mA, at least 27 mA, at least 28 mA, at least 29 mA, at least 30 mA, at least 40 mA, or at least 50 mA. In some embodiments, the fixed setting sets the electrical stimulation at a current passing through one of the one or more electrodes of at most 1 mA, at most 5 mA, at most 6 mA, at most 7 mA, at most 8 mA, at most 9 mA, at most 10 mA, at most 11 mA, at most 12 mA, at most 13 mA, at most 14 mA, at most 15 mA, at most 16 mA, at most 17 mA, at most 18 mA, at most 19 mA, at most 20 mA, at most 25 mA, at most 30 mA, at most 35 mA, at most 40 mA, at most 45 mA, at most 50 mA, at most 60 mA, at most 70 mA, at most 80 mA, at most 90 mA, or at most 100 mA. In some embodiments, the fixed setting sets the electrical stimulation at a current passing through one of the one or more electrodes of from about 0.1 mA to 60 mA. In some embodiments, the fixed setting sets the electrical stimulation at a current passing through one of the one or more electrodes of about 10 mA. In some embodiments, the fixed setting comprises a plurality of currents of from 0.01 mA to 100 mA for the electrical stimulation. In some embodiments, the fixed setting comprises a current of about 0.1 mA, about 1 mA, about 2 mA, about 3 mA, about 4 mA, about 5 mA, about 6 mA, about 7 mA, about 8 mA, about 9 mA, about 10 mA, about 11 mA, about 12 mA, about 13 mA, about 14 mA, about 15 mA, about 16 mA, about 17 mA, about 18 mA, about 19 mA, about 20 mA, about 21 mA, about 22 mA, about 23 mA, about 24 mA, about 25 mA, about 26 mA, about 27 mA, about 28 mA, about 29 mA, about 30 mA, about 40 mA, about 50 mA, about 60 mA, about 70 mA, about 80 mA, about 90 mA, or about 100 mA for the electrical stimulation. In some embodiments, the fixed setting comprises a current of about 10 mA for the electrical stimulation. In some embodiments, the power source provides a voltage of at least 0.5 V, at least 1 V, at least 5 V, at least 10 V, at least 11 V, at least 12 V, at least 13 V, at least 14 V, at least 15 V, at least 16 V, at least 17 V, at least 18 V, at least 19 V, at least 20 V, at least 21 V, at least 22 V, at least 23 V, at least 24 V, at least 25 V, at least 26 V, at least 27 V, at least 28 V, at least 29 V, at least 30 V, at least 40 V, or at least 50 V. In some embodiments, the power source provides a voltage of at most 1 V, at most 5 V, at most 6 V, at most 7 V, at most 8 V, at most 9 V, at most 10 V, at most 11 V, at most 12 V, at most 13 V, at most 14 V, at most 15 V, at most 16 V, at most 17 V, at most 18 V, at most 19 V, at most 20 V, at most 25 V, at most 30 V, at most 35 V, at most 40 V, at most 45 V, at most 50 V, at most 60 V, at most 70 V, at most 80 V, at most 90 V, or at most 100 V. In some embodiments, the power source provides a voltage of from about 5 V to about 60 V. In some embodiments, the power source provides a voltage of about 24V. In some embodiments, the fixed setting comprises a plurality of voltages of from 0.1 V to 100 V. In some embodiments, the power source is configured to provide at most 2 minutes, at most 5 minutes, at most 10 minutes, at most 30 minutes, at most 1 hour, at most 2 hours, at most 4 hours, or at most 7 hours of electrical stimulation. In some embodiments, the power source is configured to provide at least 10 seconds, at least 30 seconds, at least 1 minute, at least 2 minutes, at least 5 minutes, at least 10 minutes, at least 30 minutes, at least 1 hour, or at least 2 hours of electrical stimulation. In some embodiments, the power source is configured to provide from about 2 minutes to about 15 minutes of electrical stimulation. In some embodiments, the power source is configured to provide about 5 minutes of electrical stimulation. In some embodiments, the power source comprises one or more batteries. In some embodiments, each of the batteries has a capacity of at least 1 mAh, at least 10 mAh, at least 25 mAh, at least 50 mAh, at least 75 mAh, at least 100 mAh, at least 125 mAh, at least 150 mAh, or at least 170 mAh. In some embodiments, each of the batteries has a capacity of at most 50 mAh, at most 100 mAh, at most 150 mAh, at most 200 mAh, at most 300 mAh, or at most 500 mAh. In some embodiments, each of the batteries has a capacity of from about 10 mAh to about 200 mAh. In some embodiments, at least one of the batteries has a capacity of about 170 mAh. In some

embodiments, each of the batteries provides a voltage of at least 0.5 V, at least 1 V, at least 1.5 V, at least 2 V, at least 2.5 V, at least 3 V, at least 4 V, at least 5 V, at least 6 V, at least 7 V, at least 8 V, or at least 9 V. In some embodiments, each of the batteries provides a voltage of at most 5 V, at most 6 V, at most 7 V, at most 8 V, at most 9 V, at most 10 V, at most 11 V, at most 12 V, at most 13 V, at most 14 V, or at most 15 V. In some embodiments, each of the batteries provides a voltage of from 1.5 V to 9 V. In some embodiments, at least one of the batteries provides a voltage of about 5 V. In some embodiments, the batteries are rechargeable. In some embodiments, the batteries are non-rechargeable. In some embodiments, the batteries comprise silver-oxide batteries, alkaline batteries, lithium-ion batteries, zinc-carbon batteries, nickel- cadmium batteries, nickel metal hydride batteries, or a combination thereof. In some embodiments, the batteries are silver-oxide batteries. In some embodiments, the electrical stimulation has a waveform. In some embodiments, the waveform is shaped. In some

embodiments, the waveform is sinusoidal, square, sawtooth, or triangular. In some embodiments, the fixed setting comprises a plurality of waveforms for the electrical stimulation. In some embodiments, the fixed setting comprises a waveform that is sinusoidal, square, triangular, or sawtooth for the electrical stimulation. In some embodiments, the mechanism of activation comprises a power button. In some embodiments, the power button toggles the electrical stimulation between an on status and an off status. In some embodiments, the electrical stimulation is activated by pressing the power button. In some embodiments, the electrical stimulation is activated by sliding the power button. In some embodiments, the power button is not configured to turn off the electrical stimulation. In some embodiments, the mechanism of activation comprises pull tab activation. In some embodiments, the mechanism of activation is incapable of deactivating the electrical stimulation. In some embodiments, the mechanism of activation and the stimulation status indicator are separated. In some embodiments, the mechanism of activation and the stimulation status indicator are combined. In some

embodiments, the stimulation status indicator indicates the off status. In some embodiments, the off status is an affirmative signal comprising light, sound, or both. In some embodiments, the off status is the lack of an affirmative signal. In some embodiments, the stimulation status indicator is light-based. In some embodiments, the stimulation status indicator comprises a light-emitting diode (LED). In some embodiments, the device comprises a contact alert indicator that indicates a good electrode-skin contact, a poor electrode-skin contact, or both. In some embodiments, the contact alert indicator is located on a surface of the housing that is opposite to the skin side. In some embodiments, the contact alert indicator is light-based. In some embodiments, the contact alert indicator comprises an LED. In some embodiments, the contact alert indicator is sound- based. In some embodiments, a good electrode-skin contact is an affirmative signal comprising light, sound, or both. In some embodiments, a poor electrode-skin contact is an affirmative signal or a lack of an affirmative signal. In some embodiments, a good electrode-skin contact is a lack of an affirmative signal. In some embodiments, a poor electrode-skin contact is an affirmative signal. In some embodiments, the stimulation status indicator and the contact alert indicator are combined. In some embodiments, the stimulation status indicator and the contact alert indicator are integrated into one LED. In some embodiments, the stimulation status indicator and the contact alert indicator are separate. In some embodiments, the device is configured for a single use. In some embodiments, the electrical stimulation is predetermined or pre-programmed. [0005] In another aspect, described herein is a method of stimulating a vagus nerve of an individual in need thereof, the method comprising: positioning any of the auricular devices described on or near the external ear of the individual, thereby placing the one or more electrodes on the individual’s cymba concha and contacting the conductive material to the cymba concha; and initiating the electrical stimulation through the mechanism of activation.

[0006] In another aspect, described herein is a method of preventing ileus in an individual in need thereof, comprising (a) positioning any of the auricular devices described herein on or near the external ear of the individual, (b) initiating an electrical stimulation of a vagus nerve of an individual, wherein the electrical stimulation comprises a fixed setting comprising one or more frequencies of from 5 Hz to 60 Hz, one or more pulse widths of from 100 ps to 2000 ps, and one or more currents of from 0.01 mA to 60 mA, wherein the fixed setting is configured to stimulate C fibers without stimulating A or B fibers of the vagus nerve; (c) stimulating a C fiber of the vagus nerve for no more than 1 hour, thereby preventing ileus; and (d) ending the electrical stimulation.

[0007] In another aspect, described herein is a method of stimulating a vagus nerve of an individual in need thereof, the method comprising: (a) positioning a device on or near an external ear of the individual, wherein the device comprises: (i) an attachment configured to attach to a housing or an earbud, the attachment comprising: one or more electrodes configured to deliver electrical stimulation, and a conductive material located at a skin-side surface of the attachment; (ii) a power source configured to provide at most 8 hours of electrical stimulation; (b) placing the one or more electrodes on or near a cymba concha of the individual, thereby creating a contact between the skin-side surface of the attachment and the cymba concha; and (c) initiating the electrical stimulation through a mechanism of activation, wherein the electrical stimulation stimulates C fibers of the vagus nerve. In some embodiments, the attachment is integrated with or configured to attach to a housing, and wherein the housing is configured to anchor the device on or near the external ear. In some embodiments, the attachment is configured to attach to an earbud. In some embodiments, the attachment is configured as a sleeve.

[0008] In another aspect, described herein is a method of stimulating a vagus nerve of an individual in need thereof, the method comprising: (a) positioning a device on or near an external ear of the individual, wherein the device comprises: (i) a housing, wherein the housing is configured to anchor the device on or near the external ear; (ii) an attachment coupled to the housing, the attachment comprising: one or more electrodes configured to deliver electrical stimulation, and a conductive material located at a skin-side surface of the attachment; (iii) a power source disposed within the housing, wherein the power source is configured to provide at most 8 hours of electrical stimulation; (b) placing the one or more electrodes on or near a cymba concha of the individual, thereby creating a contact between the skin-side surface of the attachment and the cymba concha; and (c) initiating the electrical stimulation through a mechanism of activation operably coupled to the power source, wherein the electrical stimulation stimulates C fibers of the vagus nerve. In some embodiments, the electrical stimulation do not create any vibrotactile effects. In some embodiments, the electrical stimulation is initiated during an abdominal surgery procedure performed on the individual or before the individual receives an abdominal surgery procedure. In some embodiments, the electrical stimulation is initiated at least 1 minute, at least 5 minutes, at least 10 minutes, at least 30 minutes, at least 1 hour, at least 2 hours, or at least 4 hours before the abdominal surgery procedure. In some embodiments, the electrical stimulation is initiated at most 1 minute, at most 5 minutes, at most 10 minutes, at most 30 minutes, at most 1 hour, at most 2 hours, at most 4 hours, or at most 8 hours before the abdominal surgery procedure. In some embodiments, the electrical stimulation is initiated by turning on the power button. In some embodiments, the method further comprises terminating the electrical stimulation. In some embodiments, the electrical stimulation is terminated through the mechanism of activation. In some embodiments, the electrical stimulation is terminated by exhausting the power source. In some embodiments, the method further comprises initiating a second electrical stimulation.

[0009] In another aspect, described herein is a method of initiating a fixed setting of electrical stimulation delivered by a device, the method comprising: initiating an electrical stimulation having a fixed setting with a device, wherein the device comprises: (a) a housing configured to anchor the device on or near an external ear; and (b) an attachment coupled to the housing, the attachment comprising: one or more electrodes, wherein the one or more electrodes are configured to deliver the fixed setting of electrical stimulation, and a conductive material located at the skin-side surface of the attachment, wherein the fixed setting comprises one or more frequencies within a range from 0.1 Hz to 100 Hz, one or more pulse widths within a range from 1 ps to 2000 ps, and one or more currents within a range from 0.01 mA to 100 mA, and wherein the electrical stimulation stimulates the C fibers of the vagus nerve. In some embodiments, the method comprises toggling the power button to an on status. In some embodiments, the fixed setting comprises a frequency of about 25 Hz, a pulse width of about 250 ps, and a current of about 10 mA. In some embodiments, the electrical stimulation is effective in preventing ileus.

[0010] In another aspect, described herein is a device for modulating a vagus nerve in an individual in need thereof, the device comprising: (a) an electrode carrier comprising a first electrode, wherein the first electrode is configured to deliver an electrical stimulation to a laryngeal branch of a vagus nerve of an individual; (b) a casing configured to be disposed outside a body of the individual when the first electrode is placed adjacent to a larynx of the individual, wherein the casing comprises (i) a housing; (ii) a mechanism of activation configured to initiate the electrical stimulation, (iii) a stimulation status indicator coupled to the housing, wherein the stimulation status indicator is configured to indicate an on status of the device, a progress of the electrical stimulation, or both, (iv) a power source disposed within the housing, wherein the power source is configured to provide at most 8 hours of the electrical stimulation, and (v) an electrical circuit disposed within the housing, wherein the electrical circuit is operably coupled to the power source; and (c) one or more leads each comprising a proximal end and a distal end, wherein the proximal end is coupled to the electrical circuit and the distal end is coupled to the electrode. In some embodiments, the electrode carrier is configured to attach to a laryngeal delivery component. In some embodiments, the laryngeal delivery component is an endotracheal tube (ETT) that comprises a cuff balloon. In some embodiments, the device is configured to provide a fixed setting of electrical stimulation configured to simulate A fibers, B fibers, C fibers of the vagus nerve, or a combination thereof. In some embodiments, the device is configured to provide a fixed setting of electrical stimulation configured to selectively stimulate C fibers of the vagus nerve. In some embodiments, the device further comprises a second electrode configured to deliver the electrical stimulation to the laryngeal branch of the vagus nerve. In some embodiments, the device further comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, or more electrodes configured to deliver the electrical stimulation to the laryngeal branch of the vagus nerve. In some embodiments, the electrode is configured to be placed proximal to the cuff balloon. In some embodiments, the electrode carrier is configured to attach to the laryngeal delivery component through thermal fastening, adhesives, or mechanical fastening. In some embodiments, the electrode carrier is configured to be removable from the laryngeal delivery component after attachment. In some embodiments, the electrode carrier is flexible. In some embodiments, the mechanism of activation comprises a power button or a pull tab activation. In some

embodiments, the device comprises a contact alert indicator that indicates a good electrode larynx contact, a poor electrode-larynx contact, or both. In some embodiments, the contact alert indicator and the stimulation status indicator are combined. In some embodiments, the device is pre-integrated with the laryngeal delivery component.

[0011] In another aspect, described herein is a method of stimulating a vagus nerve of an individual in need thereof, the method comprising: (a) integrating any of the laryngeal delivery devices described herein with a laryngeal delivery component; (b) positioning the laryngeal delivery component in a larynx of the individual, thereby placing the first electrode in direct or indirect contact with the larynx; and (c) initiating the electrical stimulation through the mechanism of activation. In some embodiments, integrating comprises placing at least one of the electrodes on or near a distal end of the laryngeal delivery component. In some embodiments, integrating comprises attaching the electrode carrier to the laryngeal delivery component.

[0012] In another aspect, described herein is a method of stimulating a vagus nerve of an individual in need thereof, the method comprising: (a) positioning a laryngeal delivery component in a larynx of the individual; (b) integrating any of the laryngeal delivery devices described herein with the laryngeal delivery component, thereby placing the first electrode in direct or indirect contact with the larynx; and (c) initiating the electrical stimulation through the mechanism of activation. In some embodiments, integrating comprises placing at least one of the electrodes on or near a distal end of the laryngeal delivery component. In some embodiments, integrating comprises attaching the electrode carrier to the laryngeal delivery component.

[0013] In another aspect, described herein is a system for modulating a vagus nerve in an individual in need thereof, the system comprising: (a) a laryngeal delivery component comprising a proximal end, a distal end, a lumen extending therebetween, and a longitudinal axis extending from the proximal to the distal end; (b) an electrode carrier comprising a first electrode, wherein the first electrode is configured to deliver an electrical stimulation to a laryngeal branch of a vagus nerve of an individual, and wherein the electrode carrier is configured to attach to the laryngeal delivery component; (c) a casing configured to be disposed outside a body of the individual when the first electrode is placed adjacent to a larynx of the individual, wherein the casing comprises: (i) a housing, (ii) a mechanism of activation coupled to the housing, wherein the mechanism of activation is configured to initiate the electrical stimulation, (iii) a stimulation status indicator coupled to the housing, wherein the stimulation status indicator is configured to indicate an on status of the device, a progress of the electrical stimulation, or both, (iv) a power source disposed within the housing, wherein the power source is configured to provide at most 8 hours of the electrical stimulation, and (v) an electrical circuit disposed within the housing, wherein the electrical circuit is operably coupled to the power source; and (d) one or more leads each comprising a proximal end and a distal end, wherein the proximal end is coupled to the electrical circuit and the distal end is coupled to the first electrode. In some embodiments, the electrode carrier comprises 2, 3, 4, 5, 6, 7, 8, 9, 15, 20 or more electrodes. In some embodiments, the laryngeal delivery component is an endotracheal tube (ETT). In some embodiments, the laryngeal delivery component comprises a cuff balloon. In some embodiments, the electrode is placed proximal to the cuff balloon. In some embodiments, cuff balloon is situated between the electrode and the distal end of the laryngeal delivery component. In some embodiments, the electrode is housed within the laryngeal delivery component. In some embodiments, the electrode is positioned on an internal surface of the laryngeal delivery component. In some embodiments, the electrode is positioned on an external surface of the laryngeal delivery component. In some embodiments, the electrode is configured to maintain a contact with the larynx. In some embodiments, at least two electrodes are positioned parallel to the longitudinal axis of the laryngeal delivery component. In some embodiments, all electrodes are positioned parallel to the longitudinal axis of the laryngeal delivery component. In some embodiments, at least two electrodes are positioned in a pattern perpendicular to the longitudinal axis of the laryngeal delivery component. In some embodiments, all electrodes are positioned in a pattern

perpendicular to the longitudinal axis of the laryngeal delivery component. In some

embodiments, the laryngeal delivery component comprises a secondary balloon near the distal end. In some embodiments, the cuff balloon is situated between the secondary balloon and the distal end of the laryngeal delivery component. In some embodiments, the electrodes are affixed to or contained within an external or internal surface of the secondary balloon. In some embodiments, a diameter of the secondary balloon is the same as or different from a diameter of the cuff balloon. In some embodiments, the secondary balloon is configured to maintain a contact with the larynx. In some embodiments, the secondary balloon is coated with a conductive material. In some embodiments, the first electrode is in a form of a circumferential conductive coating. In some embodiments, the first electrode has a cross-section that is circular, flat, rectangle, or square. In some embodiments, the first electrode has a shape that is a wire, a bar, a dot, a cross, or a loop. In some embodiments, the first electrode is disposed in an electrode carrier. In some embodiments, the electrode carrier is attached to the laryngeal delivery component through thermal fastening, adhesives, or mechanical fastening. In some embodiments, the electrode carrier is removable from the laryngeal delivery component. In some embodiments, the electrode carrier is flexible. In some embodiments, the electrode carrier comprises conductive material. In some embodiments, the electrodes are at least partially covered by the conductive material at a side facing the larynx. In some embodiments, the system is pre-integrated. In some embodiments, the laryngeal delivery component is not pre-integrated in the system.

[0014] In another aspect, described herein is a method of stimulating a vagus nerve of an individual in need thereof, the method comprising: positioning any of the laryngeal delivery systems described herein in a larynx of the individual, thereby placing at least one of the electrodes in direct or indirect contact with the larynx; and initiating the electrical stimulation.

[0015] In another aspect, described herein is a method of initiating a fixed setting of electrical stimulation delivered by a device, the method comprising: initiating an electrical stimulation at a fixed setting with a device, wherein the device comprises: (a) an electrode carrier comprising a first electrode; (b) a casing separate from but coupled to the electrode carrier, the casing comprising: (i) a housing, (ii) a mechanism of activation, wherein the mechanism of activation operates the first electrode, (iii) a stimulation status indicator coupled to the housing, wherein the stimulation status indicator indicates an on status of the device, the progress of an electrical stimulation by the first electrode, or both, (iv) a power source disposed within the housing, wherein the power source is configured to provide at most 8 hours of the electrical stimulation, and (v) an electrical circuit disposed within the housing, wherein the electrical circuit is operably coupled to the power source and the first electrode; and (c) one or more leads each comprising a proximal end and a distal end, wherein the proximal end is coupled to the electrical circuit and the distal end is coupled to the first electrode, and wherein the fixed setting comprises one or more frequencies of from 0.1 Hz to 100 Hz, one or more pulse widths of from 1 ps to 2000 ps, and one or more currents of from 0.01 mA to 100 mA. In some embodiments, the housing is configured to be disposed outside the individual when the first electrode is placed adjacent to a larynx of the individual.

[0016] In another aspect, described herein is a method of generating a fixed setting of electrical stimulation, the method comprising: turning on a power switch of a device thereby initiating the fixed setting for an electrical stimulation, wherein the device comprises: (a) a first electrode configured to output the electrical stimulation; and (b) a casing coupled to the first electrode, the casing comprising: (i) a housing, (ii) the power switch configured to operate the first electrode at the fixed setting, (iii) a power source within the housing configured to provide at most 8 hours of the electrical stimulation, and (iv) an electrical circuit disposed within the housing, wherein the electrical circuit is operably coupled to the power source and the first electrode and defines the fixed setting of the electrical stimulation; wherein the fixed setting comprises one or more frequencies of from 0.1 Hz to 100 Hz, one or more pulse widths of from 1 ps to 2000 ps, and one or more currents of from 0.01 mA to 100 mA. In some embodiments, the device comprises a stimulation status indicator that indicates an on status of the device, the progress of an electrical stimulation by the first electrode, or both. In some embodiments, the casing of the device is configured to removably or permanently attach to an endotracheal tube. In some embodiments, the device is configured to provide a fixed setting of electrical stimulation configured to stimulate A fibers, B fibers, or C fibers of the vagus nerve, or a combination thereof. In some

embodiments, the device is configured to provide a fixed setting of electrical stimulation configured to selectively stimulate C fibers of the vagus nerve without stimulating A and B fibers of the vagus nerve.

[0017] In another aspect, described herein is the use of any of the devices or systems described herein, for modulating a vagus nerve of an individual by providing a fixed setting of electrical stimulation, wherein the fixed setting of electrical stimulation comprises one or more frequencies of from 0.1 Hz to 100 Hz, one or more pulse widths of from 1 ps to 2000 ps, and one or more currents of from 0.01 mA to 100 mA. [0018] In another aspect, described herein is a device for use in a method of stimulating a vagus nerve of an individual in need thereof, wherein the device comprises: (a) an attachment comprising: (i) one or more electrodes integrated to a body of the attachment, wherein the one or more electrodes are configured to deliver an electrical stimulation to an auricular branch of a vagus nerve, and (ii) a conductive material located at a skin-side surface of the attachment, wherein the attachment is configured to allow the one or more electrodes or the conductive material to come into contact with a skin in a cymba concha of the individual when the device is positioned on or near an external ear of the individual; and (b) a mechanism of activation operably coupled to the one or more electrodes and configured to activate the electrical stimulation, wherein, after the electrical stimulation is initiated through the mechanism of activation, the device is configured to provide a fixed setting of electrical stimulation configured to stimulate C fibers of the vagus nerve, wherein the fixed setting comprises one or more frequencies within a range of 5 Hz to 60 Hz, one or more pulse widths within a range of 100 ps to 2000 ps, and one or more currents within a range of 0.01 mA to 60 mA. In some

embodiments, the device does not create any vibrotactile effect.

[0019] In another aspect, described herein is a device for use in a method of stimulating a vagus nerve of an individual in need thereof, wherein the device comprises: (i) an electrode carrier comprising a first electrode, wherein the first electrode is configured to deliver an electrical stimulation to a laryngeal branch of a vagus nerve of an individual; and (ii) a mechanism of activation configured to activate the electrical stimulation, wherein, after the electrical stimulation is initiated through the mechanism of activation, the device is configured to provide a fixed setting of electrical stimulation configured to stimulate C fibers of the vagus nerve, wherein the fixed setting comprises one or more frequencies within a range of 5 Hz to 60 Hz, one or more pulse widths within a range of 100 ps to 2000 ps, and one or more currents within a range of 0.01 mA to 60 mA. In some embodiments, the device is configured to provide a fixed setting of electrical stimulation configured to stimulate the A, B, or C fibers of the vagus nerve. In some embodiments, the device is configured to provide a fixed setting of electrical stimulation configured to selectively stimulate C fibers of the vagus nerve without stimulating A and B fibers of the vagus nerve.

[0020] In another aspect, disclosed herein is a method of preventing ileus in an individual in need thereof by means of any of the preceding devices, systems, or methods.

BRIEF DESCRIPTION OF THE DRAWINGS

[0021] The novel features of the subject matter disclosed herein are set forth with particularity in the appended claims. A better understanding of the features and advantages of the subject matter disclosed herein will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the subject matter disclosed herein are utilized, and the accompanying drawings of which:

[0022] FIG. 1 illustrates the vagus nerve and its relevant innervations and branches, in accordance with embodiments.

[0023] FIG. 2 illustrates the anatomy of the ear, in accordance with embodiments.

[0024] FIG. 3A-FIG. 3C illustrate an auricular device that modulates the auricular branch of the vagus nerve through the external ear, in accordance with embodiments. FIG. 3A shows a front view of the device positioned in an external ear, illustrating the attachment, the housing, the post, the power button, and the stimulation status indicator. FIG. 3B shows a back plan view with the electrode(s) and conductive material displayed. FIG. 3C shows a side perspective view of the device.

[0025] FIG. 4A-FIG. 4B illustrate a design of an auricular device that modulates the auricular branch of the vagus nerve through the external ear comprising a combined power button and stimulation status indicator, in accordance with embodiments. FIG. 4A shows a front view of the device positioned in an external ear, illustrating the combined power button and stimulation status indicator. FIG. 4B shows a back plan view of the device, which is substantially equivalent to FIG. 3B.

[0026] FIG. 5A-FIG. 5B illustrate a design of an auricular device that lacks a post, in accordance with embodiments. FIG. 5A shows a front view of the device positioned in an external ear, illustrating the absence of a post. FIG. 5B shows a back plan view of the device, also illustrating the absence of a post.

[0027] FIG. 6A-FIG. 6B illustrate a design of an auricular device comprising a straight attachment, in accordance with embodiments. FIG. 6A shows a front view of the device positioned in an external ear, displaying the straight attachment. FIG. 6B shows a back plan view of the device with a straight attachment.

[0028] FIG. 7A-FIG. 7B illustrate another design of an auricular device comprising a housing that is configured to maintain position behind the external ear, in accordance with embodiments. FIG. 7A shows a front view of the device positioned in an external ear, displaying the attachment, the housing, the over-the-ear hook, and the combined power button and stimulation status indicator. FIG. 7B shows a back plan view of the curved attachment, displaying the electrode(s) and conductive material, with the over-the-ear hook not shown beyond the dotted line.

[0029] FIG. 8A-FIG. 8B illustrate yet another design of an auricular device comprising a clip that is configured to maintain the attachment in a target position of the ear, in accordance with embodiments. FIG. 8A shows a front view of the device positioned in an external ear, displaying the clip. FIG. 8B shows a back plan view of the curved attachment, with the clip not shown beyond the dotted line.

[0030] FIG. 9 illustrates a sagittal view of a laryngeal delivery system that modulates the laryngeal branch of the vagus nerve, in accordance with embodiments.

[0031] FIG. 10 illustrates a lateral view of a laryngeal delivery system at the level of laryngeal contact, displaying the electrode(s) present on or near the distal end of the device, in accordance with embodiments.

[0032] FIG. 11 illustrates a lateral view of a laryngeal delivery system at the level of laryngeal contact with the electrode(s) take the form of a circumferential conductive coating, in accordance with embodiments.

[0033] FIG. 12 illustrates a lateral view of a laryngeal delivery system at the level of laryngeal contact with the electrode(s) affixed to or integrated within the surface of a secondary balloon, in accordance with embodiments.

[0034] FIG. 13A-FIG.13B illustrate a laryngeal delivery device and system comprising electrode(s) that come pre-packaged on a flexible carrier, in accordance with embodiments. FIG. 13A shows a full view of the electrode(s) in unwrapped format. FIG. 13B shows a lateral view of the integrated laryngeal delivery system at the level of laryngeal contact.

[0035] FIG.14 illustrates a front perspective view of another design of an auricular device comprising a housing that comprises an anchoring mechanism, an attachment that comprises electrodes and a cymba concha contacting component, a mechanism of activation, and a combined contact alert indicator and stimulation status indicator, in accordance with

embodiments.

[0036] FIG.15 illustrates a front perspective view of yet another design of an auricular device comprising a housing that comprises an anchoring mechanism, an attachment that comprises electrodes and a cymba concha contacting component, a mechanism of activation, a contact alert indicator, and a stimulation status indicator, in accordance with embodiments.

[0037] FIG.16 illustrates a back perspective view of an auricular device comprising a mechanism of activation, a housing that comprises an anchoring mechanism, and an attachment that comprises electrodes and a cymba concha contacting component, in accordance with embodiments.

DETAILED DESCRIPTION

[0038] In the following detailed description, reference is made to the accompanying figures, which form a part hereof. In the figures, similar symbols typically identify similar components, unless context dictates otherwise. The illustrative embodiments described in the detailed description, figures, and claims are not meant to be limiting. Other embodiments may be utilized, and other changes may be made, without departing from the scope of the subject matter presented herein. It will be readily understood that the aspects of the present disclosure, as generally described herein, and illustrated in the figures, can be arranged, substituted, combined, separated, and designed in a wide variety of different configurations, all of which are explicitly contemplated herein.

[0039] Although certain embodiments and examples are disclosed below, inventive subject matter extends beyond the specifically disclosed embodiments to other alternative embodiments and/or uses, and to modifications and equivalents thereof. Thus, the scope of the claims appended hereto is not limited by any of the particular embodiments described below. For example, in any method or process disclosed herein, the acts or operations of the method or process may be performed in any suitable sequence and are not necessarily limited to any particular disclosed sequence. Various operations may be described as multiple discrete operations in turn, in a manner that may be helpful in understanding certain embodiments, however, the order of description should not be construed to imply that these operations are order dependent.

Additionally, the structures, systems, and/or devices described herein may be embodied as integrated components or as separate components.

[0040] For purposes of comparing various embodiments, certain aspects and advantages of these embodiments are described. Not necessarily all such aspects or advantages are achieved by any particular embodiment. Thus, for example, various embodiments may be carried out in a manner that achieves or optimizes one advantage or group of advantages as taught herein without necessarily achieving other aspects or advantages as may also be taught or suggested herein.

The present disclosure is described in relation to deployment of systems, devices, or methods for treatment of ileus. However, one of skill in the art will appreciate that this is not intended to be limiting and the devices and methods disclosed herein may be used in other anatomical areas and in other surgical procedures.

Certain Definitions

[0041] The terminology used herein is for the purpose of describing particular cases only and is not intended to be limiting. As used herein, the singular forms“a”,“an” and“the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms“comprises” and/or“comprising,” when used in this specification, specify the presence of stated features, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, steps, operations, elements, components, and/or groups thereof. As used herein, the term“and/or” includes any and all combinations of one or more of the associated listed items and may be abbreviated as

Furthermore, to the extent that the terms“including”,“includes”,“having”,“has”,“with”, or variants thereof are used in either the detailed description and/or the claims, such terms are intended to be inclusive in a manner similar to the term“comprising”.

[0042] Although the terms“first” and“second” may be used herein to describe various features/elements (including steps), these features/elements should not be limited by these terms, unless the context indicates otherwise. These terms may be used to distinguish one

feature/element from another feature/element. Thus, a first feature/element discussed below could be termed a second feature/element, and similarly, a second feature/element discussed below could be termed a first feature/element without departing from the teachings of the present disclosure.

[0043] Throughout this specification and the claims which follow, unless the context requires otherwise, the word“comprise”, and variations such as“comprises” and“comprising” means various components can be co-jointly employed in the methods and articles (e.g., compositions and apparatuses including device and methods). For example, the term“comprising” will be understood to imply the inclusion of any stated elements or steps but not the exclusion of any other elements or steps.

[0044] The term“about” or“approximately” means within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, e.g., the limitations of the measurement system. In certain embodiments, the term“about” or“approximately” means within 1, 2, 3, or 4 standard deviations. In certain embodiments, the term“about” or“approximately” means within 30%, 25%, 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.1%, or 0.05% of a given value or range.

[0045] As used herein in the specification and claims, including as used in the examples and unless otherwise expressly specified, all numbers may be read as if prefaced by the word“about” or“approximately,” even if the term does not expressly appear. The phrase“about” or “approximately” may be used when describing magnitude and/or position to indicate that the value and/or position described is within a reasonable expected range of values and/or positions. For example, a numeric value may have a value that is +/- 0.1% of the stated value (or range of values), +/- 1% of the stated value (or range of values), +/- 2% of the stated value (or range of values), +/- 5% of the stated value (or range of values), +/- 10% of the stated value (or range of values), etc. Any numerical values given herein should also be understood to include about or approximately that value, unless the context indicates otherwise. For example, if the value“10” is disclosed, then“about 10” is also disclosed. Any numerical range recited herein is intended to include all sub-ranges subsumed therein. It is also understood that when a value is disclosed that “less than or equal to” the value,“greater than or equal to the value” and possible ranges between values are also disclosed, as appropriately understood by the skilled artisan. For example, if the value“X” is disclosed the“less than or equal to X” as well as“greater than or equal to X” (e.g., where X is a numerical value) is also disclosed. It is also understood that the throughout the application, data is provided in a number of different formats, and that this data, represents endpoints and starting points, and ranges for any combination of the data points. For example, if a particular data point“10” and a particular data point“15” are disclosed, it is understood that greater than, greater than or equal to, less than, less than or equal to, and equal to 10 and 15 are considered disclosed as well as between 10 and 15. It is also understood that each unit between two particular units are also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.

[0046] The terms“individual,”“patient,” or“subject” are used interchangeably. None of the terms require or are limited to situation characterized by the supervision (e.g. constant or intermittent) of a health care worker (e.g. a doctor, a registered nurse, a nurse practitioner, a physician’s assistant, an orderly, or a hospice worker).

[0047] Images shown for the right ear may be designed and adapted for the left ear by mirroring the right ear configuration shown in the drawings.

[0048] When a feature or element is herein referred to as being“on” another feature or element, it can be directly on the other feature or element or intervening features and/or elements may also be present. In contrast, when a feature or element is referred to as being“directly on” another feature or element, there are no intervening features or elements present. It will also be understood that, when a feature or element is referred to as being“connected”,“attached” or “coupled” to another feature or element, it can be directly connected, attached or coupled to the other feature or element or intervening features or elements may be present. In contrast, when a feature or element is referred to as being“directly connected”,“directly attached” or“directly coupled” to another feature or element, there are no intervening features or elements present. Although described or shown with respect to one embodiment, the features and elements so described or shown can apply to other embodiments. It will also be appreciated by those of skill in the art that references to a structure or feature that is disposed“adjacent” another feature may have portions that overlap or underlie the adjacent feature

Technical Overview

[0049] As illustrated in FIG. 1, the vagus nerve 101 sends branches to innervate a variety of organs, including the auricular branch 102 to the ear 200, the pharyngeal branch 103 to the oropharynx 106, the superior 104 and recurrent laryngeal nerves 105 to the larynx 107, as well as multiple branches 109 to intra-abdominal organs including the intestines 108. Accordingly, the modulation of the vagus nerve 101 can be performed through any of its innervations and branches such as the auricular branch 102 in the ear 200 and the laryngeal branch 104, 105 in the larynx 107. As shown in FIG. 2, the external ear 200 is comprised of several distinct anatomical locations, including the helix 201, antihelix 202, scapha 203, triangular fossa 212, superior crus 209, inferior crus 210, cymba concha 204, cavum concha 205, tragus 206, anti -tragus 207, inter- tragic notch 211, and lobule 208, several selections of which can be utilized to stimulate the auricular branch 102 of the vagus nerve 101.

[0050] Described herein, in certain embodiments, are systems, devices, and methods that stimulate the vagus nerve 101 proper, or one of its branches (e.g., branches 102, 103, 104, 105, or 109), electrically. There are many branches of the vagus nerve 101 that can be accessed for stimulation or modulation, some of which include the auricular 102 and recurrent and superior laryngeal branches 105, 104. The applications for the presently disclosed systems, devices, and methods can include multiple inflammatory diseases, as well as for the prevention and treatment of postoperative ileus.

[0051] By modulating the electrical parameters, the users of the devices, systems, and methods described herein can select whether afferent or efferent fibers of the vagus nerve 101 are stimulated, and can also control whether the A, B, or C fibers are selectively stimulated. In some embodiments, stimulating efferent fibers has a direct effect on the target organs. In some embodiments, afferent fibers transmit centrally toward the brain 100, and stimulations are re transmitted via efferent fibers to the target organs (i.e., indirect stimulation). By stimulating the vagus nerve directly or indirectly, the parasympathetic nervous system is activated, mediated in part by the chemical neurotransmitter acetylcholine. The various potential downstream effects include, but are not limited to, activation of the enteric nervous system and/or downregulation of inflammatory cytokines.

[0052] Within the vagus nerve 101, A and B fibers are myelinated, while C fibers are generally unmyelinated and smaller in diameter than A and B fibers. In some embodiments, these fibers each represent both afferent and efferent transfer of information. Cardiac effects are most pronounced with activation of B fibers, typically at higher signal intensity than it would take to recruit A fibers. Additionally, bronchoconstriction may be experienced with activation of B fibers. Pain can be experienced when A and C fibers are recruited. Without being bound by theory, the devices, systems, and methods disclosed herein can target the stimulation of C fibers by using lower stimulation frequencies and slightly higher intensities as compared to stimulating frequencies and intensities for B fibers and/or A fibers. [0053] In some embodiments, it is an object of the present disclosure to selectively stimulate the C fibers and to limit the stimulation of A or B fibers. In some embodiments, A, B, and/or C fibers of the vagus nerve are targeted. In some embodiments, the systems, devices, and methods described herein are configured to selectively stimulate C fibers and minimize the effect to A and/or B fibers. In some embodiments, the systems, devices, and methods described herein are configured to have minimal effect on A and/or B fibers. In some embodiments, the systems, devices, and methods described herein are configured to have minimal or no cardiac effects. In some embodiments, the systems, devices, and methods described herein do not create any vibrotactile effects. In some embodiments, the systems, devices, and methods described herein do not create any anti-inflammatory effects. In some embodiments, the systems, devices, and methods described herein are configured to have minimal or no effect on bronchoconstriction. In some embodiments, stimulation of the vagus nerve using the systems, devices, and methods disclosed herein does not utilize any burst frequencies.

[0054] Without being bound by any particular theory, it is believed that in some cases a stimulation of the C fibers requires a higher voltage than the stimulation of A and/or B fibers. For example, in some embodiments, a stimulation of C fibers occurs at a voltage from about 2.5 V to about 6.7 V, from about 1 to about 10 V, or any value therebetween. In some embodiments, stimulation of A and/or B fibers occurs at a voltage that is at most 2.5 V, at most 2 V, at most 1 V, at most 0.5 V, or at most 0.25 V. Without being bound by theory, it is believed that in some cases a stimulation of the C fibers requires a lower frequency than the stimulation of A and/or B fibers. For example, in some embodiments, a stimulation of C fibers occurs at a frequency of about 2 Hz. In some embodiments, a stimulation of C fibers occurs at a frequency of at most about 50 Hz, at most about 40 Hz, at most about 30 Hz, at most about 25 Hz, at most 20 about Hz, at most about 15 Hz, at most about 10 Hz, at most about 5 Hz, or at most about 2 Hz. In some embodiments, a stimulation of A or B fibers occurs at a frequency of at least 25 Hz, at least 30 Hz, at least 40 Hz, or at least 50 Hz. Without being bound by theory, it is believed that in some cases a stimulation of the C fibers requires a lower frequency and a higher voltage than the stimulation of A and/or B fibers.

[0055] Clinical indications for the devices, systems, and methods described herein can include, but are not limited to, treatment and/or prevention of ileus, postoperative ileus, paralytic ileus, physiological ileus, gastroparesis, chronic constipation, inflammatory bowel disease, rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, psoriasis, ankylosing spondylitis, hidradenitis suppurativa, migraines, epilepsy, depression, autism, bipolar disorder, schizophrenia, CHF, tachyarrhythmias, and/or pain disorders. [0056] In some embodiments, electrical parameters are of particular importance to the devices, systems, and methods described herein, and include frequency, ranging from about 10 Hz to about 50 Hz, or greater than about 50 Hz, or less than about 10 Hz. In some embodiments, a stimulation frequency suitable for C fiber stimulation is between 2 Hz and 60 Hz, or any ranges therebetween. In some embodiments, a stimulation frequency suitable for C fiber stimulation is within a range bounded by any two of the following values: 2 Hz, 5Hz, 10 Hz, 15 Hz, 20 Hz, 25 Hz, 30 Hz, 35 Hz, 40 Hz, 45 Hz, 50 Hz, 55 Hz, and 60 Hz.

[0057] In some embodiments, the voltage is, from about 1 V to about 5 V, greater than 5 V, or less than 1 V in amplitude. In some embodiments, a stimulation voltage suitable for C fiber stimulation is between 0.5 V and 60 V or any ranges therebetween. In some embodiments, a stimulation voltage suitable for C fiber stimulation is within a range bounded by any two of the following values: 0.5 V, 1 V, 5 V, 10 V, 15 V, 20 V, 25 V, 30 V, 35 V, 40 V, 45 V, 50 V, 55 V, and 60 V.

[0058] In some embodiments, the voltage is monophasic or biphasic. In some embodiments, the current is from about 0 mA to about 1 mA or even up to 100 mA. In some embodiments, a stimulation current suitable for C fiber stimulation is between 0.1 mA and 60 mA, between 5 mA and 15 mA, or any ranges therebetween. In some embodiments, a stimulation current suitable for C fiber stimulation is within a range bounded by any two of the following values: 0.1 mA, 0.5 mA, 1 mA, 5 mA, 10 mA, 15 mA, 20 mA, 25 mA, 30 mA, 35 mA, 40 mA, 45 mA, 50 mA, 55 mA, and 60 mA.

[0059] In some embodiments, the pulse width of the signal is from about 0 ms to about 2 ms, or greater than about 2 ms. In some embodiments, a stimulation pulse width suitable for C fiber stimulation is between 100 ps and 2000 ps or any ranges therebetween. In some embodiments, a stimulation pulse width suitable for C fiber stimulation is within a range bounded by any two of the following values: 100 ps, 200 ps, 300 ps, 400 ps, 500 ps, 600 ps, 700 ps, 800 ps, 900 ps, 1000 ps, 1100 ps, 1200 ps, 1300 ps, 1400 ps, 1500 ps, 1600 ps, 1700 ps, 1800 ps, 1900 ps, and 2000 ps.

[0060] In some embodiments, the waveform is shaped. In some embodiments, the waveform includes but is not limited to the form of square waves, sinusoidal waves, sawtooth waves, or triangular waves. In some embodiments, a plurality of waveforms are utilized for the electrical stimulation.

[0061] Additional frequencies, voltages, pulse widths, wave forms, and currents suitable for C fiber stimulation are further described elsewhere herein.

Device [0062] In one aspect, disclosed herein are devices for modulating a vagus nerve in an individual in need thereof. In some embodiments, disclosed herein are devices for selectively stimulating the C fibers of the vagus nerve. In some embodiments, a device disclosed herein stimulates the A, B, and/or C fibers. A vagus nerve can be modulated through any one of its branches, including the auricular branch to the ear, the pharyngeal branch to the oropharynx, the superior and recurrent laryngeal nerves to the larynx, and multiple branches to intra-abdominal organs such as the intestines. In one aspect, disclosed herein are devices that modulate the vagus nerve through the auricular branch, i.e., auricular delivery devices. In another aspect, disclosed herein are devices that modulate the vagus nerve through the laryngeal branch, i.e., laryngeal delivery devices.

[0063] In some embodiments, the device comprises one or more electrodes that are configured to deliver electrical stimulation to a branch of the vagus nerve. In some embodiments, the device comprises a housing. In some embodiments, the device comprises an attachment coupled to the housing that comprises electrode(s) connected to the circuitry and power source and that attaches to the cymba concha. In some embodiments, the attachment is configured to couple the one or more electrodes to the skin of the cymba concha. In some embodiments, the attachment is straight, curved, or otherwise correspondingly-shaped to enable extension of the attachment to between the housing and the cymba concha. In some embodiments, the device comprises a housing and one or more electrodes. In some embodiments, the device comprises a housing, an attachment, and one or more electrodes. In some embodiments, the device comprises one or more leads. In some embodiments, the device comprises one or more leads and one or more electrodes. In some embodiments, the device further comprises a post, a conductive material, an electrical circuit, a power source, a mechanism of activation such as a power button, a stimulation status indicator, a contact alert indicator, an electrode carrier, one or more leads, or any combination thereof.

[0064] In some embodiments, an auricular delivery device (e.g., device 300 described herein) comprises a housing, an attachment, one or more electrodes, a conductive material, an electrical circuit, a power source, a mechanism of activation such as a power button, a stimulation status indicator, a contact alert indicator, or any combination thereof. In some embodiments, an auricular delivery device comprises (a) a housing; (b) an attachment coupled to the housing, the attachment comprising (i) one or more electrodes and (ii) a conductive material; (c) an electrical circuit disposed within the housing; and (d) a power source disposed within the housing. In some embodiments, an auricular delivery device further comprises a mechanism of activation such as a power button, a stimulation status indicator, or both. In some embodiments, an auricular delivery device comprises a contact alert indicator. [0065] Any of the auricular delivery devices described herein can be a single ear device or a device positioned in both ears. In some embodiments, the auricular delivery device is a device adapted to be positioned in the right ear. In some embodiments, the auricular delivery device is a device adapted to be positioned in the left ear. In some embodiments, the auricular delivery device comprises a first device adapted to be positioned in the right ear and a second device adapted to be positioned in the left ear.

[0066] In some embodiments, an auricular delivery device comprises (a) a housing, wherein the housing is configured to anchor the device on or near an external ear of the individual; (b) an attachment coupled to the housing, the attachment comprising: (i) one or more electrodes disposed on or near a skin-side surface of the attachment, wherein the electrodes are configured to deliver electrical stimulation to an auricular branch of the vagus nerve, and (ii) a conductive material located at the skin-side surface of the attachment, wherein the conductive material at least partially covers the one or more electrodes on the skin side, wherein the attachment is configured to allow the conductive material to come into contact with a skin in the individual’s cymba concha and to maintain the contact; (c) an electrical circuit disposed within the housing and operably coupled to the power source; (d) a power source disposed within the housing, wherein the power source is configured to provide at most 8 hours of electrical stimulation; (e) a mechanism of activation such as a power button coupled to the housing, wherein the mechanism of activation operates to initiate the electrical stimulation; and (f) a stimulation status indicator coupled to the housing, wherein the stimulation status indicator indicates the status of the device, the progress of the electrical stimulation, or both.

[0067] In some embodiments, a laryngeal delivery device (e.g., device 900 described herein) comprises one or more electrodes and one or more leads. In some embodiments, the laryngeal delivery device further comprises an electrode carrier for housing the electrodes. In some embodiments, a laryngeal delivery device comprises an electrode carrier and a housing. In some embodiments, a laryngeal delivery device comprises a housing and an electrode carrier that comprises a first electrode. In some embodiments, a laryngeal delivery device comprises one or more electrodes, a housing, one or more leads, a mechanism of activation such as a power button or a power switch, a stimulation status indicator, a power source, an electrical circuit, or any combination thereof. In some embodiments, a laryngeal delivery device comprises a contact alert indicator. In some embodiments, a laryngeal delivery device comprises (a) one or more electrodes, (b) a housing, (c) one or more leads, and (d) an electrical circuit disposed within the housing. In some embodiments, the laryngeal delivery device is used in combination with a laryngeal delivery component such as an ETT tube. In some embodiments, the laryngeal delivery device is coupled with a laryngeal delivery component to make an integrated laryngeal delivery system.

[0068] In some embodiments, a laryngeal delivery device comprises: (a) one or more electrodes configured to deliver electrical stimulation to a laryngeal branch of the vagus nerve of the individual, wherein the electrodes are configured to be placed on or near a distal end of a laryngeal delivery component; (b) a housing configured to be disposed outside the individual when the laryngeal delivery component is placed adjacent to a larynx of the individual; (c) one or more leads each comprising a proximal end and a distal end, wherein the proximal end is coupled to the housing and the distal end is coupled to the one or more electrodes; (d) a mechanism of activation coupled to the housing, wherein the mechanism of activation operates to initiate the electrical stimulation; (e) a stimulation status indicator coupled to the housing, wherein the stimulation status indicator indicates the status of the device, the progress of the electrical stimulation, or both; (f) a power source disposed within the housing, wherein the power source is configured to provide at most 8 hours of electrical stimulation; and (g) an electrical circuit disposed within the housing, wherein the electrical circuit is operably coupled to the one or more leads and to the power source.

Housing

[0069] In some embodiments, the described device comprises a housing (e.g., housing 302 described herein). For an auricular delivery device, the housing can be configured to anchor the device, e.g., on or near an external ear of the individual receiving the electrical stimulation. The housing can be configured to anchor the device through any mechanism. In some embodiments, the housing is configured to fit appropriately and maintain its position on or near an external ear of the individual. For example, the housing can be configured to fit appropriately in a concha cavum of the ear, thereby anchoring the device in the external ear of the individual. For another example, the housing can be configured to maintain its position in the concha cavum. The housing can have a shape that is complementary to the human concha cavum, or a portion of thereof. The housing can comprise a pliable material that conforms to the concha cavum when inserted therein. In some embodiments, the pliable material is a gel such as a hydrogel, a foam such as memory foam, or a flexible plastic or rubber-containing material. In some embodiments, the housing comprises adhesives such as adhesive stripes or pads that are configured to anchor the device to the appropriate position.

[0070] In some embodiments, the housing is configured to maintain a position behind the external ear, thereby anchoring the device in the external ear of the individual. For example, the housing can comprise an over-the-ear hook component (e.g., over-the-ear hook 701 shown in FIG. 7) that anchors the device near the ear. The over-the-ear hook component can be attached to the housing, or it can be part of the housing. In some embodiments, the housing and the attachment are connected by the over-the-ear hook component. In some embodiments, the housing comprises a clip (e.g., clip 801 shown in FIG. 8) that functions to anchor the device over the ear. The clip can be attached to the housing, or it can be part of the housing. In some embodiments, the clip is configured to anchor the device over the ear.

[0071] In some embodiments, the housing of an auricular device comprises an anchoring mechanism (e.g., anchoring mechanism 1402 shown in FIGS. 14-16). In some embodiments, the anchoring mechanism is shaped as an earplug. The earplug can function to anchor and to maintain position of the device. In some embodiments, the earplug is configured to fit appropriately in the individual’s ear canal. In some embodiments, the earplug is configured to fit appropriately in the external portion of the individual’s ear canal. In some embodiments, the housing is not anchored inside the ear canal. In some embodiments, the earplug comprises a pliable material that conforms to the ear canal of the individual when inserted therein. The pliable material can be a compressible foam such as polyurethane foam, polyethylene foam, or polyvinyl chloride foam. The pliable material can comprise silicone. The pliable material can comprise a polymer or rubber. In some embodiments, the earplug is flanged. In certain embodiments, the earplug is double-flanged or triple-flanged. In certain embodiments, an earplug, such as a flanged earplug, comprises silicone.

[0072] In some embodiments, the housing functions as an ergonomic handle, through which the device’s position can be initially set or manipulated. The device can be positioned near the auricular branch of the vagus nerve, for example, in or on the external ear. In some embodiments, the housing comprises or is coupled to a post (e.g., post 303 shown in FIGS. 3, 4, and 6). The post can function as an ergonomic handle for setting or adjusting the position of the device. In some embodiments, the post and the attachment are coupled to the housing on opposite sides. In some embodiments, one or more electrical components are disposed on or within the post. In some embodiments, the electrical circuit, the power source, the mechanism of activation (e.g., a power button or power switch), the stimulation status indicator, or a combination thereof is disposed on or within the post.

[0073] In some embodiments, the housing comprises an earbud, earphone, in-ear headphone, or the like. In some embodiments, the housing comprises an earbud, to which the attachment can be attached. In some embodiments, the attachment is permanently attached to the housing. In some embodiments, the attachment is removably attached to the housing. In some embodiments, the attachment is configured to slide on to the housing, for example in the form of a sleeve. In some embodiments, the attachment is configured to clip on to the housing. In some embodiments, the attachment is configured to stick or adhere to the housing. In some embodiments, the attachment is configured to attach to the housing as a sleeve, for example as a sleeve comprising electrodes and/or leads and configured to be removably slid on to the housing. In some embodiments, the attachment is configured to be attached to the housing by adhesives, magnetic, and/or other physical or chemical mechanism. In some embodiments, the earbud housing does not provide audio to the user. In some embodiments, the housing functions as a speaker and provides audio to the user. For example, in some embodiments, an earbud or earphone housing is configured to produce audio, such as music, before, during, and/or after the electrical stimulation. In some embodiments, the earbud or earphone is wireless (e.g., Bluetooth, wi-fi, radio-frequency, etc.). In some embodiments, the earbud or earphone is wired (e.g., comprising an auxiliary cable or auxiliary cable input, etc.). In some embodiments, the earbud or earphone is commercially available. In some embodiments, the power source is external to the earbud. In some

embodiments, the power source is integrated with the earbud. In some embodiments, the earbud, the attachment, or both are connected with a power source by one or more leads. In some embodiments, the earbud, the attachment, or both are not connected by any leads.

[0074] In some embodiments of the laryngeal delivery device, the housing is part of a casing (e.g., casing 903 shown in FIG. 9) configured to be disposed outside of the individual receiving the electrical stimulation. The laryngeal delivery component that is coupled with the device can be placed adjacent to a larynx of the individual. The housing of a laryngeal delivery device can be coupled with one or more leads (e.g., leads 904 shown in FIGS. 9 and 13) each comprising a proximal end and a distal end. In some embodiments, the proximal end of the lead is coupled to the housing and the distal end is coupled to the one or more electrodes (e.g., electrodes 306 described herein). In some embodiments, the laryngeal delivery device lacks a housing, and the one or more leads are coupled with the power source or power button on the proximal end.

Electrical Circuit

[0075] In some embodiments, the described device comprises an electrical circuit. The electrical circuit can be disposed within the housing, for example, in the post. The electrical circuit can also be disposed within the attachment. In some embodiments, the electrical circuit is operably coupled to the power source. In some embodiments, the electrical circuit is operably coupled to the one or more electrodes. In some embodiments of the laryngeal delivery device, the electrical circuit is operably coupled to the one or more leads and to the power source.

Power Source

[0076] In some embodiments, the described device comprises a power source. In other embodiments, the device does not comprise a power source, but rather utilizes an external power source, e.g., an AC outlet. For example, some embodiments of the laryngeal delivery device do not comprise a power source within the device itself. In some embodiments, the power source is disposed within the housing. In some embodiments, the power source is disposed within the post component of the housing. In some embodiments of the auricular delivery device, the power source is disposed within the attachment.

[0077] In some embodiments, the power source is configured to provide a maximum and/or a minimum duration of electrical stimulation. In some embodiments, the power source is configured to provide at most 8 hours or 24 hours of electrical stimulation. In some

embodiments, the power source is configured to provide at most 1 minute, at most 2 minutes, at most 3 minutes, at most 4 minutes, at most 5 minutes, at most 6 minutes, at most 7 minutes, at most 8 minutes, at most 9 minutes, at most 10 minutes, at most 30 minutes, at most 1 hour, at most 2 hours, at most 4 hours, or at most 7 hours of electrical stimulation. In some embodiments, the power source is configured to provide at most 2 minutes, at most 5 minutes, at most 10 minutes, at most 30 minutes, at most 1 hour, at most 2 hours, at most 4 hours, or at most 7 hours of electrical stimulation. In some embodiments, the power source is configured to provide at least 10 seconds, at least 30 seconds, at least 1 minute, at least 2 minutes, at least 3 minutes, at least 4 minutes, at least 5 minutes, at least 6 minutes, at least 7 minutes, at least 8 minutes, at least 9 minutes, at least 10 minutes, at least 30 minutes, at least 1 hour, at least 2 hours, or at least 4 hours of electrical stimulation. In some embodiments, the power source is configured to provide at least 10 seconds, at least 30 seconds, at least 1 minute, at least 2 minutes, at least 5 minutes, at least 10 minutes, at least 30 minutes, at least 1 hour, at least 2 hours, or at least 4 hours of electrical stimulation. In some embodiments, the power source is configured to provide from about 2 to about 15 minutes of electrical stimulation. In some embodiments, the power source is configured to provide about 5 minutes of electrical stimulation.

[0078] In some embodiments, the power source is configured to provide about 1 minute to about 2 hours of electrical stimulation. In some embodiments, the power source is configured to provide about 1 minute to about 5 minutes, about 1 minute to about 9 minutes, about 1 minute to about 10 minutes, about 1 minute to about 30 minutes, about 1 minute to about 60 minutes, about 5 minutes to about 9 minutes, about 5 minutes to about 10 minutes, about 5 minutes to about 30 minutes, about 5 minutes to about 60 minutes, about 9 minutes to about 10 minutes, about 9 minutes to about 30 minutes, about 9 minutes to about 60 minutes, about 10 minutes to about 30 minutes, about 10 minutes to about 60 minutes, about 30 minutes to about 60 minutes of electrical stimulation, and/or ranges therebetween. In some embodiments, the power source is configured to provide about 1 minute, about 5 minutes, about 9 minutes, about 10 minutes, about 30 minutes, or about 60 minutes of electrical stimulation. In some embodiments, the power source is configured to provide at least about 1 minute, about 5 minutes, about 9 minutes, about 10 minutes, or about 30 minutes of electrical stimulation. In some embodiments, the power source is configured to provide at most about 5 minutes, about 9 minutes, about 10 minutes, about 30 minutes, or about 60 minutes of electrical stimulation.

[0079] The power source can be configured to provide a maximum and/or a minimum voltage and/or ranges therebetween. In some embodiments, the power source provides a voltage of at least 0.5 V, at least 1 V, at least 5 V, at least 10 V, at least 11 V, at least 12 V, at least 13 V, at least 14 V, at least 15 V, at least 16 V, at least 17 V, at least 18 V, at least 19 V, at least 20 V, at least 21 V, at least 22 V, at least 23 V, at least 24 V, at least 25 V, at least 26 V, at least 27 V, at least 28 V, at least 29 V, at least 30 V, at least 40 V, or at least 50 V. In some embodiments, the power source provides a voltage of at most 1 V, at most 5 V, at most 6 V, at most 7 V, at most 8

V, at most 9 V, at most 10 V, at most 11 V, at most 12 V, at most 13 V, at most 14 V, at most 15 V, at most 16 V, at most 17 V, at most 18 V, at most 19 V, at most 20 V, at most 25 V, at most 30 V, at most 35 V, at most 40 V, at most 45 V, at most 50 V, at most 60 V, at most 70 V, at most 80 V, at most 90 V, or at most 100 V. In some embodiments, the power source provides a voltage within a range of about 0.5 V to about 100 V, about 5 V to about 60 V, and/or ranges therebetween. In some embodiments, the power source provides a voltage of about 24V.

[0080] The power source can be a voltage source or a current source. In some embodiments, the power source comprises or is one or more batteries. In some embodiments, the one or more batteries are rechargeable. In some embodiments, the one or more batteries are non-rechargeable. In some embodiments, the batteries comprise silver-oxide batteries, alkaline batteries, lithium-ion batteries, zinc-carbon batteries, nickel-cadmium batteries, nickel metal hydride batteries, or a combination thereof. In some embodiments, the batteries are silver-oxide batteries.

[0081] In some embodiments, each of the batteries has a capacity of at least 1 mAh, at least 10 mAh, at least 25 mAh, at least 50 mAh, at least 75 mAh, at least 100 mAh, at least 125 mAh, at least 150 mAh, or at least 170 mAh. In some embodiments, each of the batteries has a capacity of at most 50 mAh, at most 100 mAh, at most 150 mAh, at most 200 mAh, at most 300 mAh, or at most 500 mAh. In some embodiments, each of the batteries has a capacity of from about 10 mAh to about 200 mAh, or any ranges therebetween. In some embodiments, at least one of the batteries has a capacity of about 150 mAh, about 160 mAh, about 170 mAh, about 180 mAh, about 190 mAh, or about 200 mAh. In some embodiments, at least one of the batteries has a capacity within a range of about 10 mAh to about 200 mAh, or any ranges therebetween. In some embodiments, at least one of the batteries has a capacity of about 170 mAh.

[0082] In some embodiments, each of the batteries provides a voltage of at least 0.5 V, at least 1 V, at least 1.5 V, at least 2 V, at least 2.5 V, at least 3 V, at least 4 V, at least 5 V, at least 6 V, at least 7 V, at least 8 V, or at least 9 V. In some embodiments, each of the batteries provides a voltage of at most 5 V, at most 6 V, at most 7 V, at most 8 V, at most 9 V, at most 10 V, at most 11 V, at most 12 V, at most 13 V, at most 14 V, or at most 15 V. In some embodiments, each of the batteries provides a voltage within a range of about 0.5 V to about 15 V, about 1.5 V to about 9 V, or any ranges therebetween. In some embodiments, at least one of the batteries provides a voltage of about 5 V.

[0083] In some embodiments, the device is configured for a single use, i.e., a disposable device. The duration of electrical stimulation that the power source is configured to provide can have a maximum limit. The duration of electrical stimulation that the power source is configured to provide can also have a minimum limit. The power source can be configured to provide approximately one session of the electrical stimulation; for example, the power source of a single-use device can be configured to provide one session of electrical stimulation. The power source can also be configured to provide approximately two or more sessions of electrical stimulation. The duration of an electrical stimulation session can vary depending on the types of the device, the need of the individual, and other parameters used in the stimulation. An exemplary electrical stimulation session can last about 10 seconds, 30 seconds, 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 6 minutes, 7 minutes, 8 minutes, 9 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 1 hour, 2 hours, or 4 hours. In some embodiments, an electrical stimulation delivered by the device can last about 1 to 10 minutes, 2-8 minutes, 4-6 minutes, and/or ranges therebetween.

Mechanism of Activation and Indicators

[0084] In some embodiments, the described device comprises a mechanism of activation (e.g., mechanism of activation 1404 or power button 304 shown in FIGS. 3-9 and 14-16), a stimulation status indicator (e.g. stimulation status indicator 305 shown in FIGS. 3-9 and 14-15), or both. The mechanism of activation can be operated to initiate the electrical stimulation. In some

embodiments, the mechanism of activation comprises a pull tab, and electrical stimulation is initiated upon pulling of the tab. In some embodiments, the mechanism of activation comprises a power button. In some embodiments, the mechanism of activation comprises a power switch. Depending on the design, electrical stimulation can be initiated by pressing, rotating, or sliding the power button. In some embodiments, the mechanism of activation comprises a power switch. In certain embodiments, the mechanism of activation comprises a sliding on/off mechanism. In some embodiments, the electrical stimulation is initiated by removing a protection layer on the one or more electrodes or on the attachment.

[0085] In some embodiments, the described device further comprises a mechanism of terminating the electrical stimulation. In certain embodiments, the mechanism of terminating the stimulation is combined with the mechanism of activation. For example, in some embodiments, an on/off power button is operated to initiate and to terminate the stimulation. For another example, in some embodiments, a pull tab is used to initiate and to terminate the electrical stimulation. In certain embodiments, electrical stimulation is initiated by pulling a tab and terminated by exhausting the power source, without the need for an off signal to be sent by the tab (or other mechanism). In some embodiments, the mechanism of activation such as a power button or power switch is coupled to the housing. In some embodiments, the power button (or power switch) is operated to initiate the electrical stimulation, terminate the electrical

stimulation, or both. In some embodiments, the power button (or power switch) toggles the electrical stimulation between an on status and an off status.

[0086] In some embodiments, the stimulation status indicator is coupled to the housing. The stimulation status indicator is configured to indicate the status of the device, the progress of the electrical stimulation, or both. For example, the stimulation status indicator indicated whether the electrical stimulation is on or off, whether the electrical stimulation is complete, the power level of the device, the passed or remaining time for the electrical stimulation or a percentage thereof, or a combination of the above.

[0087] In some embodiments, the mechanism of activation (e.g., a power button or power switch), the stimulation status indicator, or both are housed in or coupled with any suitable component of the device. For example, in some embodiments of an auricular delivery device, the mechanism of activation and the stimulation status indicator are each be independently disposed on the housing or on the attachment. In some embodiments, the mechanism of activation, the stimulation status indicator, or both are disposed on or within the post. For another example, in some embodiments of a laryngeal delivery device, the mechanism of activation and the stimulation status indicator are each be independently disposed on the housing or on the one or more leads. In some embodiments, the mechanism of activation and the stimulation status indicator are disposed on the housing. In some embodiments of an auricular device, the stimulation status indicator is located on the side surface of the housing. In some embodiments of an auricular device, the stimulation status indicator is located on the surface of the housing that is opposite to the skin side.

[0088] In some embodiments, the mechanism of activation and the stimulation status indicator are combined. In other embodiments, the mechanism of activation and the stimulation status indicator are separated. In some embodiments, the device comprises two or more mechanisms of activation; for example, a first mechanism of activation which operates to initiate the stimulation and a second mechanism of activation which operates to terminate the stimulation. In some embodiments, the device comprises two or more stimulation status indicators; for example, a first indicator configured to signal the status of the device and a second indicator configured to signal the progress of the stimulation. [0089] In some embodiments, the stimulation status indicator indicates the on status, the off status, or both. In some embodiments, the on status is indicated by an affirmative signal such as a light or sound. In some embodiments, the on status is indicated by a lack of affirmative signal. In some embodiments, the off status is indicated by an affirmative signal such as a light or sound. In some embodiments, the off status is indicated by a lack of affirmative signal. In some

embodiments, the on status, off status, or both are indicated by a pattern of the signal, e.g., the flashing pattern of the light or varying tunes of the sound.

[0090] In some embodiments, the stimulation status indicator is configured to use light, sound, or both to provide a status indication. In some embodiments, the stimulation status indicator is light- based. In some embodiments, the status indication is signaled by the presence or absence of light, by the color the light, and/or by the flashing pattern of the light. In some embodiments, the stimulation status indicator comprises a light-emitting diode (LED). In some embodiments, the stimulation status indicator is sound-based. In some embodiments, the status indication is signaled by the presence or absence of sound, by the duration or (such as a short tone(s), prolonged tone(s), etc.), and/or by the pattern of the sound (patterned tones, musical phrases, recorded phrases, or the like). In some embodiments, the stimulation status indicator is a buzzer, a noise-emitting diode, a speaker, or the like. For example, in some embodiments, the housing comprises an earbud which provides audio (e.g., music) to the user to indicate that stimulation is on or off.

[0091] In some embodiments, the described device comprises a contact alert indicator (e.g., contact alert indicator 1401 shown in FIGS. 14 and 15). In some embodiments, the contact alert indicator indicates a good electrode-skin contact, a poor electrode-skin contact, or both. In some embodiments of a laryngeal device, the contact alert indicator indicates a good electrode-larynx contact, a poor electrode-larynx contact, or both. The contact alert indicator can be situated in any suitable position of the device as will be understood by one of ordinary skill in the art based on the teachings herein.

[0092] In some embodiments, the contact alert indicator is located on the housing. For example, in some embodiments of an auricular device, the contact alert indicator is located on a surface of the housing that is opposite to the skin side surface. In some embodiments of an auricular device, the contact alert indicator is located on the side of the housing. In some embodiments, good contact, either between the electrode-skin or electrode-larynx, is indicated by an affirmative signal such as light and/or sound. In some embodiments, poor contact, either between the electrode-skin or electrode-larynx, is indicated by an affirmative signal such as light and/or sound. In some embodiments, both good and poor contact conditions are indicated by affirmative signals. For example, in some embodiments, good and poor contact conditions are indicated by two different light signals. In some embodiments, poor contact, either between the electrode-skin or electrode-larynx, is indicated by the lack of an affirmative signal. For example, in some embodiments, a good contact is indicated by a light signal and a poor contact is indicated by the lack of a light signal. In some embodiments, good contact, either between the electrode-skin or electrode-larynx, is indicated by the lack of an affirmative signal. In some embodiments, poor contact is indicated by an affirmative signal. For example, in some embodiments, poor contact is indicated by a sound signal and good contact is indicated by silence. In some embodiments, a good contact, a poor contact, or both are indicated by a pattern of the signal, e.g., the flashing pattern of the light or varying tunes of the sound. In some embodiments, the contact alert indicator is light-based. For example, in certain embodiments, the contact alert indicator comprises an LED. In some embodiments, the contact alert indicator is sound-based. In some embodiments, the device comprises two contact alert indictors, a first indicator for indicating good contact and the other for indicating poor contact.

[0093] In certain embodiments, the stimulation status indicator and the contact alert indicator are combined. For example, in some embodiments, the stimulation status indicator and the contact alert indicator are integrated into one LED. In some embodiments, the stimulation status indicator and the contact alert indicator are separate.

Attachment

[0094] In some embodiments, the described device comprises an attachment. For example, some embodiments of an auricular delivery device comprise an attachment coupled to the housing. In some embodiments, the attachment comprises one or more electrodes. In some embodiments, the attachment comprises a conductive material. In some embodiments, the attachment comprises one or more electrodes and one or more conductive materials.

[0095] In some embodiments of an auricular delivery device, the attachment is configured to fit appropriately in the cymba concha of the individual. In some embodiments, the attachment is configured to conform to the shape of the cymba concha. In some embodiments, the attachment has one or more skin-side surfaces, i.e., surfaces facing the skin of the cymba concha, and one or more outer surfaces, i.e., surfaces other than the skin-side surfaces. In some embodiments, the attachment has one or more areas that are in direct contact with the skin. In some embodiments, the attachment extends from the housing and curves toward the right (as viewed by an observer when placed in the right ear of a user) in the right ear device, thereby positioning the in-use device in the cymba concha. In some embodiments, the attachment extends from the housing and curves toward the left (as viewed by an observer when placed in the left ear of a user) in the right ear device, thereby positioning the in-use device in the cymba concha. In some embodiments, the attachment curves towards the cheeks of the user in a right ear device, left ear device, and/or both. In some embodiments, the attachment does not curve. In some embodiments, the straight attachment extends at an angle relative to the longitudinal axis of the body. In some

embodiments, the attachment is angled toward the face of the user in either the right or left ear devices, or both. In some embodiments, the straight attachment extends upwards from the housing toward the top of the head (generally along the longitudinal axis) such that at least a portion of the cymba concha is contacted by the attachment. In some embodiments, the straight attachment can be used to contact the cymba concha of either the right or the left ear when placed therein.

[0096] In some embodiments, the one or more electrodes (e.g., electrodes 306 described herein) are disposed on or near a skin-side surface (e.g., surface 308 described herein) of the attachment (e.g., attachment 301 described herein). For example, in some embodiments all of the electrodes are placed on the skin-side surface. In some embodiments, the attachment comprises a cymba concha contacting component (e.g., cymba concha contacting component 1403 shown in FIGS. 14-16) that is configured to contact the cymba concha. In some embodiments, the cymba concha contacting component is on the skin-side surface of the attachment. In some embodiments, the cymba concha contacting component comprises an area that contacts the skin. In some embodiments, the one or more electrodes are disposed on the area that contacts the skin, e.g., on the cymba concha contacting component. The one or more electrodes are configured to be disposed on any suitable component of the device, where they are configured to deliver electrical stimulation to the vagus nerve. In some embodiments, the one or more electrodes are disposed on or near a skin-side surface of the attachment, where the electrodes are configured to deliver electrical stimulation to an auricular branch of the vagus nerve.

[0097] In some embodiments, a conductive material (e.g., conductive material 307 described herein) is disposed on one or more surfaces of the attachment, e.g., at the skin-side surfaces and/or on the cymba concha contacting component. In some embodiments, the conductive material is placed on all or selected surfaces of the attachment that contact the skin. In some embodiments, the attachment is configured to allow the conductive material to come into contact with a skin in the individual’s cymba concha and to maintain the contact. In some embodiments, the one or more electrodes are fully or partially covered by the conductive material. In some embodiments, the one or more electrodes are at least partially covered by the conductive material on the skin side. In some embodiments, the one or more electrodes are fully covered by the conductive material thereby preventing any direct skin to electrode contact. In some

embodiments, the conductive material is placed between the skin and the electrodes. In some embodiments, the conductive material is arranged in a continuous or non-continuous pattern, for example, stripes, squares, circles, etc. [0098] In some embodiments, the attachment comprises a non-conductive material. In some embodiments, the non-conductive material is disposed on a surface of the attachment that is opposite to the skin side. In some embodiments, the non-conductive material is disposed on the outer surfaces.

[0099] In certain embodiments, the attachment consists essentially of a conductive material. In further embodiments, the attachment is made of conductive material, i.e., the attachment is one electrode. In some embodiments, the conductive material is a conductive gel or a conductive polymer such as conductive silicone. In some embodiments, the attachment or the device does not comprise electrically conductive fluid. In some embodiments, the conductive material does not comprise electrically conductive fluid. In some embodiments, the conductive material is a flexible material. In certain embodiments, the attachment is made entirely of conductive material. In some embodiments, the attachment is an electrode.

[0100] In some embodiments, the attachment comprises a rigid material. In some embodiments, the attachment comprises a flexible material. In some embodiments, the attachment comprises a pliable material that conforms to the ear when inserted therein. In some embodiments, the attachment is covered or coated by a pliable material. In some embodiments, the pliable material is a gel (e.g., a hydrogel or conductive hydrogel), a foam (e.g., polyurethane), and/or or a flexible plastic or rubber-containing material. In some embodiments, the flexible material is a conductive polymer, such as conductive silicone. In some embodiments, the attachment is semi-flexible. In some embodiments, the attachment is stretchable. The attachment can have various shapes; for example, it can be of any shape that fits appropriately into the cymba concha. In some

embodiments, the attachment has a curved shape. In some embodiments, the attachment has a straight shape.

[0101] In some embodiments, the attachment comprises an adhesive layer. In some

embodiments, the adhesive layer is biocompatible. In some embodiments, the adhesive layer is configured to partially or fully cover the conductive material. Alternatively, or in combination, in some embodiments the adhesive layer is disposed on the outer surfaces. In some embodiments, the adhesive layer is used to maintain the contact between the conductive material and the skin.

[0102] In some embodiments, the attachment is permanently attached to a housing. In some embodiments, the attachment is removably attached to the housing. In some embodiments, the attachment comprises a sleeve configured to slide onto the housing. In some embodiments, the sleeve comprises one or more electrodes and optionally one or more leads. In some

embodiments, sliding the sleeve attachment onto the housing positions the one or more electrodes on the skin-side surface of the housing such that they are able to contact the cymba concha when the device is placed in an ear. In some embodiments, the attachment is configured to clip on to the housing. In some embodiments, the clip comprises one or more electrodes and optionally one or more leads. In some embodiments, clipping the clip attachment onto the housing positions the one or more electrodes on the skin-side surface of the housing such that they are able to contact the cymba concha when the device is placed in an ear. In some embodiments, the attachment is configured to attach to the housing by physical or chemical force such as adhesion and/or magnetic force. In some embodiments, the attachment comprises a sticker configured to stick or adhere to the housing. In some embodiments, the sticker comprises one or more electrodes and optionally one or more leads. In some embodiments, adhering the sticker attachment onto the housing positions the one or more electrodes on the skin-side surface of the housing such that they are able to contact the cymba concha when the device is placed in an ear. In some embodiments, the housing is an earbud, earphone, in-ear headphone, or the like as described herein. In some embodiments, coupling the attachment to the earbud housing does not interfere with the native audio function of the earbud.

Laryngeal Delivery Component

[0103] In some embodiments, the laryngeal delivery component is a device configured to access the larynx of an individual, e.g., a laryngeal tube or other airway management devices. In some embodiments, the laryngeal delivery component is an infraglottic device. In some embodiments, the laryngeal delivery component is an endotracheal tube (ETT) (e.g., endotracheal tube 901 described herein). In some embodiments, the laryngeal delivery component has a proximal end, a distal end, a lumen extending therebetween, and a longitudinal axis extending from the proximal end to the distal end. A person of ordinary skill in the art would appreciate that, in some embodiments, the laryngeal delivery component encompasses components that are configured to deliver the electrode(s) to other bodily cavities as well.

[0104] In some embodiments, the laryngeal delivery component comprises a cuff balloon (e.g., cuff balloon 902 shown in FIGS. 9-13). In some embodiments, the cuff balloon is located near the distal end of the laryngeal delivery component. In some embodiments, the one or more electrodes are configured to be placed proximal to the cuff balloon. In some embodiments, the one or more electrodes are configured to be placed near the distal end of the laryngeal delivery component. In some embodiments, the cuff balloon is situated between the one or more electrodes and the distal end of the laryngeal delivery component. In some embodiments, the electrodes are situated between the cuff balloon and the distal end of the laryngeal delivery component.

[0105] In some embodiments, the laryngeal delivery component comprises a secondary balloon (e.g., secondary balloon 1201 shown in FIG. 12) near the distal end of the laryngeal delivery component. In some embodiments, the cuff balloon is situated between the secondary balloon and the distal end of the laryngeal delivery component. In other embodiments, the secondary balloon is situated between the cuff balloon and the distal end of the laryngeal delivery component.

[0106] In some embodiments, the one or more electrodes are affixed to or contained within an external or internal surface of the secondary balloon. In some embodiments, the one or more electrodes are affixed to an external surface of the secondary balloon. In some specific embodiments, the one or more electrodes are located on the great circle of the secondary balloon. In some embodiments, a diameter of the secondary balloon is equal to the diameter of the cuff balloon. In some embodiments, a diameter of the secondary balloon is larger or smaller than the diameter of the cuff balloon. In some embodiments, the secondary balloon is configured to maintain a contact with the larynx. In some embodiments, the secondary balloon is coated with a conductive material. In some embodiments, the conductive material is configured to have a direct contact with the larynx. In some embodiments, the electrodes are at least partially covered by the conductive material at a side facing the larynx.

[0107] In some embodiments, the laryngeal delivery device is pre-integrated with the laryngeal delivery component. In other embodiments, the laryngeal delivery device is coupled with the laryngeal delivery component before the use of the device.

Electrode Carrier

[0108] In some embodiments of the laryngeal delivery device, the one or more electrodes are disposed in an electrode carrier. In some embodiments, the electrode carrier is configured to attach to the laryngeal delivery component. The electrode carrier can be configured to attach to the laryngeal delivery component through any suitable means such as thermal fastening, adhesives, or mechanical fastening. In some embodiments, the electrode carrier comprises a sleeve configured to slide onto the laryngeal delivery component. In some embodiments, the electrode carrier is configured to clip on to the laryngeal delivery component. In some embodiments, the electrode carrier comprises a sticker configured to stick or adhere to the laryngeal delivery component. In some embodiments, the electrode carrier is configured to be removable from the laryngeal delivery component after attachment.

[0109] In some embodiments of the auricular delivery device, the one or more electrodes are disposed in an electrode carrier. In some embodiments, the electrode carrier is configured to attach to the housing, e.g., an earbud. The electrode carrier can be configured to attach to the housing through any suitable means such as thermal fastening, adhesives, magnetic, or mechanical fastening. In some embodiments, the attachment comprises the electrode carrier. In some embodiments, the electrode carrier comprises a sleeve configured to slide onto the housing. In some embodiments, the electrode carrier is configured to clip on to the housing. In some embodiments, the electrode carrier comprises a sticker configured to stick or adhere to the housing. In some embodiments, the electrode carrier is configured to be removable from the housing after attachment.

[0110] In some embodiments, the electrode carrier is flexible. The electrode carrier can comprise the conductive material. The electrode carrier can also comprise the pliable material. In some embodiments, the electrodes are embedded in the electrode carrier.

Electrodes and Conductive Material

[0111] Herein described devices can comprise one or more electrodes (e.g., electrodes 306 described herein) that are configured to deliver electrical stimulation. In some embodiments or an auricular delivery device, the electrodes are configured to deliver stimulation to the auricular branch of the vagus nerve. In some embodiments of a laryngeal delivery device, the electrodes are configured to deliver electrical stimulation to a laryngeal branch of the vagus nerve; for example, the electrodes can be placed near the larynx. In some embodiments, the device comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more electrodes. In some embodiments, the device comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, or more electrodes. In some embodiments, the device comprises a first electrode. In some embodiments, the device comprises a first electrode and a second electrode. In some embodiments, the device comprises a first electrode, a second electrode, and additional electrode(s). In some

embodiments, the attachment, made of conductive material, is an electrode.

[0112] In some embodiments of the auricular delivery device, the electrodes are disposed on or within the attachment. In some embodiments of a laryngeal delivery device, the electrodes are disposed on or within the electrode carrier. In some embodiments, the electrodes take the form of an electrode array such as platinum iridium cuff electrode array and/or stainless-steel electrode array. In some embodiments, the electrodes are transcutaneous electrodes, such as patch electrodes. In some embodiments, the electrodes, optionally in combination with the conductive material, are configured to position on the skin or larynx of the individual.

[0113] In one aspect, described herein is an auricular delivery device configured to provide an electrical stimulation that stimulates the C fibers, the device comprising an attachment that is configured to attach to a housing or an earbud. In some embodiments, the attachment comprises one or more electrodes configured to deliver electrical stimulation and a conductive material located at a skin-side surface of the attachment. In some embodiments, the attachment is configured as a sleeve or sticker that attaches to a housing or an earbud. In some embodiments of an auricular delivery device, the electrodes are integrated into a sleeve or sticker attachment or electrode carrier as described herein. In some embodiments, the sleeve or sticker comprises or is part of the attachment. In some embodiments, the sleeve or sticker is attached to a pre-existing attachment in a cymba concha. In some embodiments, the electrodes clip to a housing, e.g., an earbud. In some embodiments, the electrodes are integrated with the attachment before being coupled to the housing. In some embodiments of an auricular delivery device, the electrodes are connected through one or more leads to a separate controller device. In some embodiments, the controller device is not integrated with the housing, e.g., the earbud. In some embodiments, the electrodes are not connected with one or more leads.

[0114] The electrodes can have a shape. In some embodiments, at least one of the electrodes has the shape of a loop, a cross, a bar, a dot, a screw, or a wire. In some embodiments, at least one of the electrodes is a bar-shaped electrode. In some embodiments, at least one of the electrodes is a dot-shaped electrode. In some embodiments, at least one of the electrodes has the shape of a screw that is flattened on it tip. In some embodiments, all the electrodes are bar-shaped or dot shaped. In some embodiments, the electrodes are in a form of a conductive coating, for example, circumferential conductive coating. In some embodiments, at least one of the electrodes has a cross-section that is circular, flat, rectangle, or square. In some embodiments, the electrodes are connected with the electrical circuit and/or power source through one or more leads. In some embodiments, the one or more leads are connected to an external controller.

[0115] In some embodiments, the device comprises a conductive material that is suitable to be used in transcutaneous simulation. In some embodiments, the conductive material is placed between the one or more electrodes and the skin of the individual. In some embodiments, the conductive material comprises a conductive textile such as those made of conductive yarns or those made of metal stands woven into regular textiles. In some embodiments, the conductive material comprises conductive gel, conductive polymer, conductive liquid, metal, alloy, carbon black, or a combination thereof. In some embodiments, the conductive material comprises a conductive wet gel. In some embodiments, the conductive material comprises metal carbide. In some embodiments, the conductive material comprises conductive gel, water, ionic liquid, or alcohol. In some embodiments, the conductive material comprises hydrogel. In some

embodiments, the hydrogel comprises polyethylene glycol. In some embodiments, the conductive material is conductive silicone. In some embodiments, the conductive material is biocompatible.

Electrical Stimulation

[0116] In some embodiments, the electrical stimulation operates on a fixed setting of electrical parameters such as frequency, pulse width, current, etc. In some embodiments, the fixed setting comprises a plurality of frequencies, pulse widths, currents, waveforms, or voltages. In some embodiments, the fixed setting comprises a single frequency, pulse width, current, waveform, or voltage. In some embodiments, the fixed setting is adjustable by the user; for example, in the laryngeal delivery device. In some embodiments, a user cannot adjust the fixed setting in an auricular delivery device.

[0117] The parameters of the electrical stimulation can be adjusted to target the A, B, or C fibers. In some embodiments, the parameters are adjusted to target the C fibers. In some embodiments, a selective stimulation of the C fibers requires a higher voltage than the stimulation of A or B fibers. In some embodiments, the electrical stimulation has a voltage from about 2.5 V to about 6.7 V, from about 1 to about 10 V, and/or any values therebetween. In some embodiments, the electrical stimulation has a voltage of about 2 V, about 3 V, about 4 V, about 5 V, about 6 V, about 7 V, about 8 V, about 9 V, or about 10 V. In some embodiments, stimulation of A or B fibers requires a voltage that is at most 2.5 V, at most 2 V, at most 1 V, at most 0.5 V, or at most 0.25 V. In some embodiments, a selective stimulation of the C fibers requires a lower frequency than the stimulation of A or B fibers. In some embodiments, a selective stimulation of C fibers requires a frequency of about 2 Hz. In some embodiments, a selective stimulation of C fibers requires a frequency of at most about 50 Hz, at most about 40 Hz, at most about 30 Hz, at most about 25 Hz, at most 20 about Hz, at most about 15 Hz, at most about 10 Hz, at most about 5 Hz, at most about 5 Hz, at most about 4 Hz, at most about 3 Hz, at most about 2.5 Hz, or at most about 2 Hz. In some embodiments, a selective stimulation of A or B fibers requires a frequency of at least 25 Hz, at least 30 Hz, at least 40 Hz, or at least 50 Hz.

[0118] In some embodiments, the electrical stimulation delivered by the device has a frequency. In some embodiments, the electrical stimulation has a frequency of at least at least 0.1 Hz, at least 1 Hz, at least 2 Hz, at least 3 Hz, at least 4 Hz, at least 5 Hz, at least 6 Hz, at least 7 Hz, at least 8 Hz, at least 9 Hz, at least 10 Hz, at least 11 Hz, at least 12 Hz, at least 13 Hz, at least 14 Hz, at least 15 Hz, at least 16 Hz, at least 17 Hz, at least 18 Hz, at least 19 Hz, at least 20 Hz, at least 21 Hz, at least 22 Hz, at least 23 Hz, at least 24 Hz, at least 25 Hz, at least 26 Hz, at least 27 Hz, at least 28 Hz, at least 29 Hz, at least 30 Hz, at least 40 Hz, or at least 50 Hz. In some embodiments, the electrical stimulation has a frequency of at most 5 Hz, at most 6 Hz, at most 7 Hz, at most 8 Hz, at most 9 Hz, at most 10 Hz, at most 11 Hz, at most 12 Hz, at most 13 Hz, at most 14 Hz, at most 15 Hz, at most 16 Hz, at most 17 Hz, at most 18 Hz, at most 19 Hz, at most 20 Hz, at most 21 Hz, at most 22 Hz, at most 23 Hz, at most 24 Hz, at most 25 Hz, at most 26 Hz, at most 27 Hz, at most 28 Hz, at most 29 Hz, at most 30 Hz, at most 35 Hz, at most 40 Hz, at most 45 Hz, at most 50 Hz, at most 60 Hz, at most 70 Hz, at most 80 Hz, at most 90 Hz, or at most 100 Hz . In some embodiments, the electrical stimulation has a frequency of from about 5 to 60 Hz, and/or ranges therebetween. In some embodiments, the electrical stimulation has a frequency of about 25 Hz. [0119] In some embodiments, the fixed setting sets the electrical stimulation at a frequency of at least 0.1 Hz, at least 1 Hz, at least 2 Hz, at least 3 Hz, at least 4 Hz, at least 5 Hz, at least 6 Hz, at least 7 Hz, at least 8 Hz, at least 9 Hz, at least 10 Hz, at least 11 Hz, at least 12 Hz, at least 13 Hz, at least 14 Hz, at least 15 Hz, at least 16 Hz, at least 17 Hz, at least 18 Hz, at least 19 Hz, at least 20 Hz, at least 21 Hz, at least 22 Hz, at least 23 Hz, at least 24 Hz, at least 25 Hz, at least 26 Hz, at least 27 Hz, at least 28 Hz, at least 29 Hz, at least 30 Hz, at least 40 Hz, or at least 50 Hz. In some embodiments, the fixed setting sets the electrical stimulation at a frequency of at most 5 Hz, at most 6 Hz, at most 7 Hz, at most 8 Hz, at most 9 Hz, at most 10 Hz, at most 11 Hz, at most 12 Hz, at most 13 Hz, at most 14 Hz, at most 15 Hz, at most 16 Hz, at most 17 Hz, at most 18 Hz, at most 19 Hz, at most 20 Hz, at most 21 Hz, at most 22 Hz, at most 23 Hz, at most 24 Hz, at most 25 Hz, at most 26 Hz, at most 27 Hz, at most 28 Hz, at most 29 Hz, at most 30 Hz, at most 35 Hz, at most 40 Hz, at most 45 Hz, at most 50 Hz, at most 60 Hz, at most 70 Hz, at most 80 Hz, at most 90 Hz, or at most 100 Hz. In some embodiments, the fixed setting sets the electrical stimulation at a frequency within a range of about 5 Hz to about 60 Hz. In some embodiments, the fixed setting sets the electrical stimulation at a frequency of about 1 Hz to about 50 Hz. In some embodiments, the fixed setting sets the electrical stimulation at a frequency of about 1 Hz to about 10 Hz, about 1 Hz to about 25 Hz, about 1 Hz to about 35 Hz, about 1 Hz to about 50 Hz, about 10 Hz to about 25 Hz, about 10 Hz to about 35 Hz, about 10 Hz to about 50 Hz, about 25 Hz to about 35 Hz, about 25 Hz to about 50 Hz, or about 35 Hz to about 50 Hz, and/or ranges therebetween. In some embodiments, the fixed setting sets the electrical stimulation at a frequency of about 1 Hz, about 10 Hz, about 25 Hz, about 35 Hz, or about 50 Hz. In some embodiments, the fixed setting sets the electrical stimulation at a frequency of at least about 1 Hz, about 10 Hz, about 25 Hz, or about 35 Hz. In some embodiments, the fixed setting sets the electrical stimulation at a frequency of at most about 10 Hz, about 25 Hz, about 35 Hz, or about 50 Hz. In some embodiments, the fixed setting sets the electrical stimulation at a frequency of about 25 Hz. In some embodiments, the fixed setting comprises a plurality of frequencies within a range of 0.1 Hz to 100 Hz for the electrical stimulation, and/or ranges therebetween.

[0120] In some embodiments, the fixed setting comprises a frequency of about 0.1 Hz, about 1 Hz, about 2 Hz, about 3 Hz, about 4 Hz, about 5 Hz, about 6 Hz, about 7 Hz, about 8 Hz, about 9 Hz, about 10 Hz, about 11 Hz, about 12 Hz, about 13 Hz, about 14 Hz, about 15 Hz, about 16

Hz, about 17 Hz, about 18 Hz, about 19 Hz, about 20 Hz, about 21 Hz, about 22 Hz, about 23

Hz, about 24 Hz, about 25 Hz, about 26 Hz, about 27 Hz, about 28 Hz, about 29 Hz, about 30

Hz, about 35 Hz, about 40 Hz, about 45 Hz, about 50 Hz, about 60 Hz, about 70 Hz, about 80

Hz, about 90 Hz, or about 100 Hz for the electrical stimulation. In some embodiments, the fixed setting comprises a frequency of about 25 Hz. [0121] In some embodiments, the electrical stimulation is delivered with a pulse width. In some embodiments, the electrical stimulation has a pulse width of at least 1 ps, at least 10 ps, at least 50 ps, at least 100 ps, at least 150 ps, at least 200 ps, at least 250 ps, at least 300 ps, at least 350 ps, at least 400 ps, at least 450 ps, or at least 500 ps. In some embodiments, the electrical stimulation has a pulse width of at most 100 ps, at most 150 ps, at most 200 ps, at most 250 ps, at most 300 ps, at most 350 ps, at most 400 ps, at most 500 ps, at most 600 ps, at most 700 ps, at most 800 ps, at most 900 ps, at most 1000 ps, at most 1500 ps, at most 2000 ps, at most 5000, or at most 20,000 ps. In some embodiments, the electrical stimulation has a pulse width of at most 100 ps, at most 150 ps, at most 200 ps, at most 250 ps, at most 300 ps, at most 350 ps, at most 400 ps, at most 500 ps, at most 600 ps, at most 700 ps, at most 800 ps, at most 900 ps, at most 1000 ps, at most 1500 ps, or at most 2000 ps. In some embodiments, the electrical stimulation has a pulse width within a range of about 100 ps to about 2000 ps, and/or ranges therebetween.

In some embodiments, the electrical stimulation has a pulse width of about 250 ps.

[0122] In some embodiments, the fixed setting sets the electrical stimulation at a pulse width of at least 1 ps, at least 10 ps, at least 50 ps, at least 100 ps, at least 150 ps, at least 200 ps, at least 250 ps, at least 300 ps, at least 350 ps, at least 400 ps, at least 450 ps, or at least 500 ps. In some embodiments, the fixed setting sets the electrical stimulation at a pulse width of at most 100 ps, at most 150 ps, at most 200 ps, at most 250 ps, at most 300 ps, at most 350 ps, at most 400 ps, at most 500 ps, at most 600 ps, at most 700 ps, at most 800 ps, at most 900 ps, at most 1000 ps, at most 1500 ps, or at most 2000 ps. In some embodiments, the fixed setting sets the electrical stimulation at a pulse width of from about 100 ps to about 2000 ps, and/or ranges therebetween. In some embodiments, the fixed setting sets the electrical stimulation at a pulse width of about 250 ps. In some embodiments, the fixed setting comprises a plurality of pulse widths of from 1 ps to 2000 ps for the electrical stimulation, and/or ranges therebetween. In some embodiments, the fixed setting comprises a pulse width of about 1 ps, about 10 ps, about 50 ps, about 100 ps, about 150 ps, about 200 ps, about 210 ps, about 220 ps, about 230 ps, about 240 ps, about 250 ps, about 260 ps, about 270 ps, about 280 ps, about 290 ps, about 300 ps, about 350 ps, about 400 ps, about 450 ps, about 500 ps, about 600 ps, about 700 ps, about 800 ps, about 900 ps, or about 1000 ps for the electrical stimulation. In some embodiments, the fixed setting sets the electrical stimulation at a pulse width of about 50 ps to about 1,000 ps. In some embodiments, the fixed setting sets the electrical stimulation at a pulse width of about 50 ps to about 100 ps, about 50 ps to about 250 ps, about 50 ps to about 500 ps, about 50 ps to about 1,000 ps, about 100 ps to about 250 ps, about 100 ps to about 500 ps, about 100 ps to about 1,000 ps, about 250 ps to about 500 ps, about 250 ps to about 1,000 ps, or about 500 ps to about 1,000 ps, and/or ranges therebetween. In some embodiments, the fixed setting comprises a pulse width of about 250 ps for the electrical stimulation.

[0123] In some embodiments, an electric current passes through the electrodes during the electrical stimulation. The current can be constant or variable. In some embodiments, the electrical stimulation has a current passing through one of the electrodes of at least 0.01 mA, at least 0.1 mA, at least 1 mA, at least 2 mA, at least 3 mA, at least 4 mA, at least 5 mA, at least 6 mA, at least 7 mA, at least 8 mA, at least 9 mA, at least 10 mA, at least 11 mA, at least 12 mA, at least 13 mA, at least 14 mA, at least 15 mA, at least 16 mA, at least 17 mA, at least 18 mA, at least 19 mA, at least 20 mA, at least 21 mA, at least 22 mA, at least 23 mA, at least 24 mA, at least 25 mA, at least 26 mA, at least 27 mA, at least 28 mA, at least 29 mA, at least 30 mA, at least 40 mA, or at least 50 mA. In some embodiments, the electrical stimulation has a current passing through one of the electrodes of at most 1 mA, at most 5 mA, at most 6 mA, at most 7 mA, at most 8 mA, at most 9 mA, at most 10 mA, at most 11 mA, at most 12 mA, at most 13 mA, at most 14 mA, at most 15 mA, at most 16 mA, at most 17 mA, at most 18 mA, at most 19 mA, at most 20 mA, at most 25 mA, at most 30 mA, at most 35 mA, at most 40 mA, at most 45 mA, at most 50 mA, at most 60 mA, at most 70 mA, at most 80 mA, at most 90 mA, or at most

100 mA. In some embodiments, the electrical stimulation has a current passing through one of the electrodes of from about 0.1 mA to about 60 mA, and/or ranges therebetween. In some embodiments, the electrical stimulation has a current passing through one of the electrodes of about 10 mA.

[0124] In some embodiments, the fixed setting sets the electrical stimulation at a current passing through one of the electrodes of at least 0.01 mA, at least 0.1 mA, at least 1 mA, at least 2 mA, at least 3 mA, at least 4 mA, at least 5 mA, at least 6 mA, at least 7 mA, at least 8 mA, at least 9 mA, at least 10 mA, at least 11 mA, at least 12 mA, at least 13 mA, at least 14 mA, at least 15 mA, at least 16 mA, at least 17 mA, at least 18 mA, at least 19 mA, at least 20 mA, at least 21 mA, at least 22 mA, at least 23 mA, at least 24 mA, at least 25 mA, at least 26 mA, at least 27 mA, at least 28 mA, at least 29 mA, at least 30 mA, at least 40 mA, or at least 50 mA. In some embodiments, the fixed setting sets the electrical stimulation at a current passing through one of the electrodes of at most 1 mA, at most 5 mA, at most 6 mA, at most 7 mA, at most 8 mA, at most 9 mA, at most 10 mA, at most 11 mA, at most 12 mA, at most 13 mA, at most 14 mA, at most 15 mA, at most 16 mA, at most 17 mA, at most 18 mA, at most 19 mA, at most 20 mA, at most 25 mA, at most 30 mA, at most 35 mA, at most 40 mA, at most 45 mA, at most 50 mA, at most 60 mA, at most 70 mA, at most 80 mA, at most 90 mA, or at most 100 mA. In some embodiments, the fixed setting sets the electrical stimulation at a current passing through one of the electrodes of from about 0.1 mA to about 60 mA, and/or ranges therebetween. In some embodiments, the fixed setting sets the electrical stimulation at a current passing through one of the electrodes of about 10 mA.

[0125] In some embodiments, the fixed setting comprises a plurality of currents within a range of 0.01 mA to 100 mA for the electrical stimulation. In some embodiments, the fixed setting comprises a current of about 0.1 mA, about 1 mA, about 2 mA, about 3 mA, about 4 mA, about 5 mA, about 6 mA, about 7 mA, about 8 mA, about 9 mA, about 10 mA, about 11 mA, about 12 mA, about 13 mA, about 14 mA, about 15 mA, about 16 mA, about 17 mA, about 18 mA, about 19 mA, about 20 mA, about 21 mA, about 22 mA, about 23 mA, about 24 mA, about 25 mA, about 26 mA, about 27 mA, about 28 mA, about 29 mA, about 30 mA, about 40 mA, about 50 mA, about 60 mA, about 70 mA, about 80 mA, about 90 mA, or about 100 mA for the electrical stimulation. In some embodiments, the fixed setting sets the electrical stimulation at a current passing through one of the electrodes of about 1 mA to about 50 mA. In some embodiments, the fixed setting sets the electrical stimulation at a current passing through one of the electrodes of about 1 mA to about 5 mA, about 1 mA to about 10 mA, about 1 mA to about 25 mA, about 1 mA to about 50 mA, about 5 mA to about 10 mA, about 5 mA to about 25 mA, about 5 mA to about 50 mA, about 10 mA to about 25 mA, about 10 mA to about 50 mA, or about 25 mA to about 50 mA, and/or ranges therebetween. In some embodiments, the fixed setting comprises a current of about 10 mA for the electrical stimulation.

[0126] In some embodiments, the electrical stimulation has a waveform. The waveform can be periodic, and it can be shaped. The waveform can have a shape that is sinusoidal, square, triangular, or sawtooth. In some embodiments, the waveform is sinusoidal, square, or triangular. In some embodiments, the fixed setting comprises a plurality of waveforms for the electrical stimulation. In some embodiments, the fixed setting comprises a waveform that is sinusoidal, square, triangular, or sawtooth for the electrical stimulation.

[0127] In some embodiments, the electrical stimulation is predetermined or pre-programmed. In other embodiments, the parameters of the electrical stimulation are set by the users individually. In some embodiments, the parameters of the electrical stimulation are adjustable.

Methods of Modulating Vagus Nerve

[0128] In one aspect, disclosed herein is a method of stimulating a vagus nerve of an individual in need thereof. The method can comprise positioning the described device near a branch of the vagus nerve and initiating the device. In some embodiments, the method comprises delivering and/or initiating an electrical stimulation with a frequency, current, and pulse width as described herein. In some embodiments, the method comprises actuating A, B, and/or C fibers of the vagus nerve. In some embodiments, the method comprises actuating C fibers while minimizing the effect on A or B fibers. In some embodiments, the method comprises (a) positioning the auricular delivery device on or near an external ear of the individual and (b) initiating the electrical stimulation. In some embodiments, the method comprises (a) positioning a device on or near an external ear of the individual; (b) placing the one or more electrodes on the individual’s cymba concha, thereby creating a contact between the conductive material and the cymba concha; and (c) initiating the electrical stimulation, wherein the electrical stimulation comprises a frequency, current, and pulse width as described herein. In some embodiments, the method comprises stimulating A, B, and/or C fibers of the vagus nerve. In some embodiments, the method comprises selectively stimulating C fibers with minimal effect on A or B fibers.

[0129] In some embodiments, the method comprises integrating the attachment with the housing. For example, in some embodiments, the method comprises attaching an attachment comprising a sleeve, sticker, or clip to the housing. In some embodiments, the housing is a pre-existing earbud (e.g., a commercially-available earbud for listening to music) configured to be positioned on or in an ear of a subject. In some embodiments, the method further comprises removing the attachment from the housing.

[0130] In some embodiments, the method comprises activating a device positioned in the right ear of a subject. In some embodiments, the method comprises activating a device positioned in the left ear of a subject. In some embodiments, the method comprises activating a device positioned in the right ear of a subject and a device positioned in the left ear of the subject. In some embodiments, the device positioned in the right ear and the device positioned in the left ear deliver simultaneous electrical stimulation. In some embodiments, the device positioned in the right ear and the device positioned in the left ear are activated simultaneously or sequentially. In some embodiments, the device positioned in the right ear and the device positioned in the left ear do not deliver electrical stimulation at the same time.

[0131] In some embodiments, the electrical stimulation is initiated by turning on the power button or power switch or other mechanism of activation described herein. In some

embodiments, the electrical stimulation is initiated by pulling a tab. The electrical stimulation can be initiated remotely, for example, via a software application that can access the device. In some embodiments, the method comprises positioning the auricular delivery device by placing the housing in the concha cavum. In some embodiments, the device is positioned by utilizing the clip. In some embodiments, when the device comprises an adhesive layer, the method can comprise removing a release liner.

[0132] In some embodiments, the method comprises (a) positioning a device on or near an external ear of the individual, wherein the device comprises (i) a housing, wherein the housing is configured to anchor the device on or near the external ear; (ii) an attachment coupled to the housing, the attachment comprising: one or more electrodes that are configured to deliver el ectri cal stimulation, and a conductive material located at the skin-side surface of the attachment, wherein the one or more electrodes are at least partially covered by the conductive material on the skin side; (iii) a power source disposed within the housing, wherein the power source is configured to provide at most 8 hours of electrical stimulation; (b) placing the one or more electrodes on the individual’s cymba concha, thereby creating a contact between the conductive material and the cymba concha; and (c) initiating the electrical stimulation e.g., by turning on the power source.

[0133] In some embodiments, the method of using the laryngeal delivery device comprises integrating the laryngeal delivery device with the laryngeal delivery component. In some embodiments, the method comprises positioning the described system in a larynx of the individual, thereby placing at least one of the electrodes in direct or indirect contact with the larynx and initiating the electrical stimulation. In some embodiments, the method of using the laryngeal delivery device comprises: (a) integrating the laryngeal delivery device with the laryngeal delivery component; (b) positioning the laryngeal delivery component in the larynx of the individual, thereby placing at least one of the electrodes near the larynx; and (c) initiating the electrical stimulation. In some embodiments, the method of using the laryngeal delivery device comprises: (a) positioning a laryngeal delivery component in a larynx of the individual; (b) integrating the laryngeal delivery device with the laryngeal delivery component, thereby placing at least one of the electrodes near the larynx; and (c) initiating the electrical stimulation. In some embodiments, the method comprises placing at least one of the electrodes in direct or indirect contact with the larynx. In some embodiments, the method comprises placing the conductive material in direct contact with the larynx.

[0134] In one aspect, disclosed herein are methods of preventing or treating a disease or disorder associated with vagus nerve, e.g., ileus, postoperative ileus, paralytic ileus, physiological ileus, gastroparesis, chronic constipation, inflammatory bowel disease, rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, psoriasis, ankylosing spondylitis, hidradenitis suppurativa, migraines, epilepsy, depression, autism, bipolar disorder, schizophrenia, CHF, tachyarrhythmias, and pain disorders. In some embodiments, the electrical simulation is applied to an individual to prevent or treat ileus. In another aspect, disclosed herein is a method of preventing ileus in an individual in need thereof by means of any of the preceding devices, systems, or methods.

[0135] Common causes of ileus can include abdominal or pelvis surgery and medication. In some embodiments, the electrical stimulation is initiated during an abdominal surgery procedure performed on the individual. In some embodiments, the electrical stimulation is initiated before the individual receives an abdominal surgery procedure. In some embodiments, the electrical stimulation is applied after the individual receives abdominal surgery procedure. In some embodiments, an individual receives the electrical stimulation both before and during the abdominal procedure. In some embodiments, an individual can receive the electrical stimulation before or during taking certain medications.

[0136] In some embodiments, the electrical stimulation described herein is effective in preventing ileus. In some embodiments, the electrical stimulation described herein is effective in treating ileus. In some embodiments, the electrical stimulation described herein modulates the A, B, and/or C fibers of the vagus nerve. In some embodiments, the electrical stimulation described herein selectively modulates the C fibers of the vagus nerve. In some embodiments, the electrical stimulation described herein is ineffective in modulating A or B fibers of the vagus nerve. In some embodiments, the electrical stimulation described herein has no cardiac effect. In some embodiments, the electrical stimulation described herein has no anti-inflammatory effect.

[0137] In some embodiments, the electrical stimulation is initiated at least 1 minute, at least 5 minutes, at least 10 minutes, at least 30 minutes, at least 1 hour, at least 2 hours, or at least 4 hours before the abdominal surgery procedure. In some embodiments, the electrical stimulation is initiated at most 1 minute, at most 5 minutes, at most 10 minutes, at most 30 minutes, at most 1 hour, at most 2 hours, at most 4 hours, or at most 8 hours before the abdominal surgery procedure.

[0138] In some embodiments, the duration of the electrical stimulation is about 1 minute to about 60 minutes. In some embodiments, the duration of the electrical stimulation is about 1 minute to about 2 minutes, about 1 minute to about 5 minutes, about 1 minute to about 10 minutes, about 1 minute to about 30 minutes, about 1 minute to about 60 minutes, about 2 minutes to about 5 minutes, about 2 minutes to about 10 minutes, about 2 minutes to about 30 minutes, about 2 minutes to about 60 minutes, about 5 minutes to about 10 minutes, about 5 minutes to about 30 minutes, about 5 minutes to about 60 minutes, about 10 minutes to about 30 minutes, about 10 minutes to about 60 minutes, or about 30 minutes to about 60 minutes, and/or any ranges therebetween. In some embodiments, the duration of the electrical stimulation is about 1 minute, about 2 minutes, about 5 minutes, about 10 minutes, about 30 minutes, or about 60 minutes. In some embodiments, the duration of the electrical stimulation is at least about 1 minute, about 2 minutes, about 5 minutes, about 10 minutes, or about 30 minutes. In some embodiments, the duration of the electrical stimulation is at most about 2 minutes, about 5 minutes, about 10 minutes, about 30 minutes, or about 60 minutes.

[0139] In some embodiments, the electrical stimulation is continuous. In some embodiments, the electrical stimulation is non-continuous. In some embodiments, the electrical stimulation is intermittent. In some embodiments, the electrical stimulation comprises more than one fixed setting of electrical stimulation. In some embodiments, the electrical stimulation comprises one or more cycles of on and off sessions. In some embodiments, the electrical stimulation comprises intermittent off cycles.

[0140] In some embodiments, the method further comprises terminating the electrical stimulation. The electrical stimulation can be terminated by any means. For example, in some embodiments the electrical stimulation is terminated by moving the device away from the individual, by turning off the power button (or power switch), by a remote application, and/or by exhausting the power source. In some embodiments, the electrical stimulation is terminated by turning off the power button or power source. In some embodiments, the electrical stimulation is terminated by exhausting the power source. In some embodiments, some individuals receive more than one session of the electrical stimulation. Accordingly, in some embodiments, the method comprises initiating a second session (or more) of the electrical stimulation.

[0141] In one aspect, disclosed herein is a method of operating a device. In some embodiments, the method comprises initiating a fixed setting of electrical stimulation. In some embodiments, the method comprises turning on a power button or power switch of the device, thereby initiating the electrical stimulation. In some embodiments, the device comprises a housing configured to anchor the device on or near an external ear. In some embodiments, the device comprises an attachment coupled to the housing. In some embodiments, the attachment comprises one or more electrodes, e.g., the first electrode, which is or are configured to deliver a fixed setting of electrical stimulation. In some embodiments, the attachment comprises a conductive material located at the skin-side surface of the attachment. In some embodiments, the attachment comprises an electrode carrier configured to position the one or more electrodes on the skin-side surface of the attachment. In some embodiments, the one or more electrodes are disposed on a skin-side surface of the attachment. In some embodiments, the fixed setting comprises one or more frequencies of from 0.1 Hz to 100 Hz, one or more pulse widths of from 1 ps to 2000 ps, and one or more currents of from 0.01 mA to 100 mA. In some embodiments, the method comprises toggling the power button or power switch to an on status. In some embodiments, the fixed setting comprises a frequency of about 25 Hz, a pulse width of about 250 ps, and a current of about 10 mA. In some embodiments, the electrical stimulation is effective in preventing ileus.

[0142] A method of preventing ileus in an individual in need thereof, comprising (i) positioning any of the described auricular device on or near the external ear of the individual, (ii) initiating an electrical stimulation of a vagus nerve of an individual, wherein the electrical stimulation comprises a fixed setting comprising one or more frequencies of from 5 Hz to 60 Hz, one or more pulse widths of from 100 ps to 2000 ps, and one or more currents of from 0.01 mA to 60 mA, wherein the fixed setting is configured to stimulate C fibers without stimulating A or B fibers of the vagus nerve; (iii) stimulating a C fiber of the vagus nerve for no more than 1 hour, thereby preventing ileus; and (iv) ending the electrical stimulation.

[0143] In one aspect, described herein is a device for use in a method of stimulating a vagus nerve of an individual in need thereof, wherein the device comprises an attachment, a conductive material located at a skin-side surface of the attachment, and a mechanism of activation. In some embodiments, the attachment comprises (i) one or more electrodes integrated to a body of the attachment, wherein the one or more electrodes are configured to deliver an electrical stimulation to an auricular branch of a vagus nerve, and (ii) a conductive material located at a skin-side surface of the attachment. In some embodiments, the attachment is configured to allow the one or more electrodes or the conductive material to come into contact with a skin in a cymba concha of the individual when the device is positioned on or near an external ear of the individual. In some embodiments, the mechanism of activation is operably coupled to the one or more electrodes and configured to activate the electrical stimulation, wherein, after the electrical stimulation is initiated through the mechanism of activation, the device is configured to provide a fixed setting of electrical stimulation configured to stimulate C fibers of the vagus nerve. In some

embodiments, the device is configured to provide a fixed setting of electrical stimulation configured to stimulate the A, B, and/or C fibers of the vagus nerve. In some embodiments, the device is configured to provide a fixed setting of electrical stimulation configured to selectively stimulate the C fibers of the vagus nerve, without stimulating A and B fibers. In some

embodiments, the fixed setting comprises one or more frequencies of from 5 Hz to 60 Hz, one or more pulse widths of from 100 ps to 2000 ps, and one or more currents of from 0.01 mA to 60 mA. In some embodiments, the device for use in a method of stimulating a vagus nerve does not create any vibrotactile effect.

[0144] In one aspect, described herein is a device for use in a method of stimulating a vagus nerve of an individual in need thereof, wherein the device comprises: an electrode carrier comprising a first electrode and a mechanism of activation configured to activate an electrical stimulation. In some embodiments, the first electrode is configured to deliver an electrical stimulation to a laryngeal branch of a vagus nerve of an individual. In some embodiments, after the electrical stimulation is initiated through the mechanism of activation, the device is configured to provide a fixed setting electrical stimulation configured to stimulate C fibers of the vagus nerve. In some embodiments, the device is configured to provide a fixed setting of electrical stimulation configured to stimulate the A, B, and/or C fibers of the vagus nerve. In some embodiments, the device is configured to provide a fixed setting of electrical stimulation configured to selectively stimulate the C fibers of the vagus nerve, without stimulating A and B fibers. In some embodiments, the fixed setting comprises one or more frequencies of from 5 Hz to 60 Hz, one or more pulse widths of from 100 ps to 2000 ps, and one or more currents of from 0.01 mA to 60 mA.

Systems

[0145] In one aspect, disclosed herein are systems for modulating the vagus nerve. In some embodiments, the systems are configured to stimulate the A, B, and/or C fibers of the vagus nerve. In some embodiments, the systems are configured to selectively stimulate C fibers of the vagus nerve without affecting A and/or B fibers as described herein. The system can comprise any of the described devices in combination with a software application. For example, in some embodiments the software application can be used to control the device remotely. In some embodiments, the software application also, or alternatively, functions as a power button, a stimulation status indicator, or both. In some embodiments the system is pre-integrated. In some embodiments, the system is not pre-integrated.

[0146] A system for laryngeal delivery can comprise a laryngeal delivery device and a laryngeal delivery component. Such a system can be pre-integrated, or it can be integrated before the use of the system. In some embodiments, the integration is implemented by placing at least one of the electrodes on or near a distal end of the laryngeal delivery component. In some embodiments, the integration is implemented by attaching the electrode carrier to the laryngeal delivery component.

[0147] In some embodiments, the laryngeal delivery system comprises one or more electrodes, an electrode carrier, one or more leads, and a laryngeal delivery component. In some

embodiments, the system further comprises a housing, a mechanism of activation such as a power button (or power switch), a stimulation status indicator, an electrical circuit, a contact alert indicator, or any combination thereof. In some embodiments, the laryngeal delivery system comprises: (a) a laryngeal delivery component; (b) one or more electrodes configured to deliver electrical stimulation to a laryngeal branch of the vagus nerve of the individual; (c) a housing configured to be disposed outside the individual when the laryngeal delivery component is placed adjacent to a larynx of the individual; (d) one or more leads each comprising a proximal end and a distal end, wherein the proximal end is coupled to the housing and the distal end is coupled to the one or more electrodes; (e) a mechanism of activation such as a power button (or power switch) coupled to the housing; (f) a stimulation status indicator coupled to the housing; (g) a power source disposed within the housing; (h) an electrical circuit disposed within the housing, wherein the electrical circuit is operably coupled to the one or more leads and to the power source, or a combination thereof.

[0148] In some embodiments of the laryngeal delivery system, the electrodes are housed within the laryngeal delivery component. For example, in some embodiments, the electrodes are positioned on an internal surface of the laryngeal delivery component. For another example, in some embodiments, the electrodes are positioned on an external surface of the laryngeal delivery component. In some embodiments, the electrodes are configured to maintain a contact with the larynx. The contact between the electrodes and the larynx can be direct or indirect. In some embodiments, the electrodes are covered by the conductive material on the larynx -facing side. In some embodiments, the conductive material is directly contacting the larynx.

[0149] The electrodes can be placed on the laryngeal delivery component in a predetermined pattern. In some embodiments, at least two electrodes are positioned parallel to the longitudinal axis of the laryngeal delivery component. In some embodiments, all electrodes are positioned parallel to the longitudinal axis of the laryngeal delivery component. In some embodiments, at least two electrodes are positioned in a pattern perpendicular to the longitudinal axis of the laryngeal delivery component. In some embodiments, all electrodes are positioned in a pattern perpendicular to the longitudinal axis of the laryngeal delivery component. In some

embodiments, the electrodes are positioned in a helical pattern along the longitudinal axis of the laryngeal delivery component.

[0150] The electrode carrier in a laryngeal delivery system can be attached to the laryngeal delivery component. In some embodiments, the electrode carrier is attached to the laryngeal delivery component through thermal fastening, adhesives, or mechanical fastening. In some embodiments, the electrode carrier is removable from the laryngeal delivery component.

[0151] A system for auricular delivery can comprise (i) one or more electrodes integrated into an attachment, wherein the attachment is configured as a sleeve or a sticker, and (ii) an earbud to which the attachment attaches. In some embodiments, the earbud is a commercially available. In some embodiments, the sleeve or sticker is attached to a pre-existing attachment in a cymba concha.

EXAMPLES

Example 1: Auricular Delivery Device as Shown in FIGS. 3A-3C

[0152] An exemplary embodiment of the auricular delivery device 300, shown in FIG. 3A-FIG. 3C, comprises (a) housing 302 designed to contain electrical components of circuitry, with a form factor that allows the device to remain anchored in the external ear 200 by fitting in the concha cavum 205, (b) curved attachment 301 shaped and made of a semi-flexible material that ensures that when the device 300 is inserted in the external ear 200, the electrodes 306 will come into contact with the skin of the cymba concha 204 and maintain their position in this target location through mechanisms such as friction, adhesion, and/or mechanical tension, (c) bar or dot electrode(s) 306 carried on the back (skin-side) surface 308 of the attachment that will deliver the electrical stimulation, (d) conductive material 307 such as a hydrogel applied on the back (skin- side) surface 308 of the attachment and electrodes 306 that ensures optimal electrical contact between the skin of the cymba concha 204 and electrodes 306, (e) a post 303 that is contained in, or connected to, the housing 302 and may contain additional electronic components as well as provide an ergonomic handle through which the position of device 300 can be initially set or manipulated; this post 303 may also provide the base on which the power button 304 (or other mechanism of activation) and/or stimulation status indicator 305 are housed; (f) power button 304 which may be used to initiate and terminate the stimulation protocol, and (g) stimulation status indicator 305 (which may be light-based as described herein) will indicate whether the device 300 is on or off, and the progress of the stimulation protocol. The structure can be mirrored for the left ear, respectively.

Example 2: Auricular Delivery Device as Shown in FIGS. 4A-4B

[0153] An exemplary embodiment of the auricular delivery device 300, shown in FIG. 4A-FIG. 4B, comprises (a) housing 302 designed to contain electrical components of circuitry, with a form factor that allows the device 300 to remain anchored in the external ear 200 by fitting snugly in the concha cavum 205, (b) curved attachment 301 shaped and made of a semi-flexible material that ensures that when the device 300 is inserted in the external ear 200, the electrodes 306 will come into contact with the skin of the cymba concha 204 and maintain their position in this target location through mechanisms such as friction, adhesion, and/or mechanical tension, (c) bar or dot electrode(s) 306 carried on the back (skin-side) surface 308 of the attachment 301 that will deliver the electrical stimulation, (d) conductive material 307 such as a hydrogel applied on the back (skin-side) surface 308 of the attachment 301 and electrodes 306 that ensures optimal electrical contact between the skin of the cymba concha 204 and electrodes 306, (e) a post 303 that is contained in, or connected to, the housing 302 and may contain additional electronic components in addition to providing an ergonomic handle through which the position of device 300 can be initially set or manipulated; this post 303 may also provide the base on which the power button/stimulation status indicator 304, 305 is housed; (f) combined power button 304 (or other mechanism of activation) and stimulation status indicator 305 will be used to initiate and terminate the stimulation protocol as well as indicate whether the device 300 is on or off and the progress of the stimulation protocol. The back of the device 300 shown in FIG. 4B looks substantially similar to the back of the device shown in FIG. 3B. The structure can be mirrored for the left ear, respectively.

Example 3: Auricular Delivery Device as Shown in FIGS. 5A-5B [0154] An exemplary embodiment of the auricular delivery device 300, shown in FIG. 5A-FIG. 5B, comprises (a) housing 302 designed to contain electrical components of circuitry, with a form factor that allows the device 300 to remain anchored in the external ear 200 by fitting snugly in the concha cavum 205 and simultaneously acts as an ergonomic handle to set and manipulate position of the device 300 in the external ear 200, without a post-like structure, (b) curved attachment 301 shaped and made of a semi-flexible material that ensures that when the device 300 is inserted in the external ear 200, the electrodes 306 will come into contact with the skin of the cymba concha 204 and maintain their position in this target location through mechanisms such as friction, adhesion, and/or mechanical tension, (c) bar or dot electrode(s) 306 carried on the back (skin-side) surface 308 of the attachment 301 that will deliver the electrical stimulation, (d) conductive material 307 such as a hydrogel applied on the back (skin-side) surface 308 of the attachment 301 and electrodes 306 that ensures optimal electrical contact between the skin of the cymba concha 204 and electrodes 306, (e) combined power button 304 (or other mechanism of activation) and stimulation status indicator 305 attached to the housing 302 that will be used to initiate and terminate the stimulation protocol as well as indicate whether the device 300 is on or off and the progress of the stimulation protocol. The structure can be mirrored for the left ear, respectively.

Example 4: Auricular Delivery Device as Shown in FIGS. 6A-6B

[0155] An exemplary embodiment of the auricular delivery device 300, shown in FIG. 6A-FIG. 6B, comprises (a) housing 302 designed to contain electrical components of circuitry, with a form factor that allows the device 300 to remain anchored in the external ear 200 by fitting snugly in the concha cavum 205, (b) straight attachment 301 shaped and made of a semi-flexible material that ensures that when the device 300 is inserted in the external ear 200, the electrodes 306 will come into contact with the skin of the cymba concha 204 and maintain their position in this target location through mechanisms such as friction, adhesion, and/or mechanical tension, (c) bar or dot electrode(s) 306 carried on the back (skin-side) surface 308 of the attachment 301 that will deliver the electrical stimulation, (d) conductive material 307 such as a hydrogel applied on the back (skin-side) surface 308 of the attachment 301 and electrodes 306 that ensures optimal electrical contact between the skin of the cymba concha 204 and electrodes 306, (e) a post 303 that is contained in, or connected to, the housing and may contain additional electronic components in addition to providing an ergonomic handle through which the position of device 300 can be initially set or manipulated; this post 303 may also provide the base on which the power button/stimulation status indicator 304, 305 are housed; (f) combined power button 304 (or other mechanism of activation) and stimulation status indicator 305 will be used to initiate and terminate the stimulation protocol as well as indicate whether the device 300 is on or off and the progress of the stimulation protocol. The structure can be mirrored for the left ear, respectively.

Example 5: Auricular Delivery Device as Shown in FIGS. 7A-7B

[0156] An exemplary embodiment of the auricular delivery device 300, shown in FIG. 7A-FIG. 7B, comprises (a) housing 302 designed to contain electrical components of circuitry, with a form factor that maintains position behind the external ear 200, and acts as an ergonomic handle to set and manipulate position of the device 300 in the external ear 200, and also acts as a base for a power button/ stimulation status indicator 304, 305, (b) an over-the-ear hook component 701 attached to, or part of, the housing 302, that anchors the device 300 near the ear 200, (c) curved attachment 301 coupled to over-the-ear hook component 701 and shaped and made of a semi- flexible material that ensures that when inserted in the external ear 200, the electrodes 306 will come into contact with the skin of the cymba concha 204 and maintain the position of the device 300 in this target location through mechanisms such as friction, adhesion, and/or mechanical tension, (d) bar or dot electrode(s) 306 carried on the back (skin-side) surface 308 of the attachment 301 that will deliver the electrical stimulation, (e) conductive material 307 such as a hydrogel applied on the back (skin-side) surface 308 of the attachment 301 and electrodes 306 that ensures optimal electrical contact between the skin of the cymba concha 204 and electrodes 306, (f) combined power button 304 (or other mechanism of activation) and stimulation status indicator 305 will be used to initiate and terminate the stimulation protocol as well as indicate whether the device 300 is on or off and the progress of the stimulation protocol. The over-the-ear hook is not shown beyond the dotted line in FIG. 7B. The structure can be mirrored for the left ear, respectively.

Example 6: Auricular Delivery Device as Shown in FIGS. 8A-8B

[0157] An exemplary embodiment of the auricular delivery device 300, shown in FIG. 8A-FIG. 8B, comprises (a) housing 302 designed to contain electrical components of circuitry, with a form factor that allows the device 300 to remain anchored in the external ear 200 by fitting snugly in the concha cavum 205 and simultaneously acts as an ergonomic handle to set and manipulate position of the device 300 in the external ear 200, and acts as a base for the power button/light; without a post and connected instead to a clip 801 used to anchor the device 300 in the target location, (b) curved attachment 301 shaped and made of a semi-flexible material that ensures that when inserted in the external ear 200, the electrodes 306 will come into contact with the skin of the cymba concha 204 and maintain the position of the device 300 in this target location through mechanisms such as friction, adhesion, and/or mechanical tension, (c) bar or dot electrode(s) 306 carried on the back (skin-side) surface 308 of the attachment 301 that will deliver the electrical stimulation, (d) conductive material 307 such as a hydrogel applied on the back (skin-side) surface 308 of the attachment 301 and electrodes 306 that ensures optimal electrical contact between the skin of the cymba concha 204 and electrodes 306, (e) combined power button 304 (or other mechanism of activation) and stimulation status indicator 305 will be used to initiate and terminate the stimulation protocol as well as indicate whether the device 300 is on or off and the progress of the stimulation protocol, (f) clip 801 attached to the housing 302 that anchors the device 300 over the ear 200 in the target position. The clip is not shown beyond the dotted line in FIG. 8B. The structure can be mirrored for the left ear, respectively.

Example 7: Laryngeal Delivery Device as Shown in FIG. 9

[0158] An exemplary embodiment of the laryngeal delivery device is configured as shown in FIG. 9. FIG. 9 illustrates a sagittal view of the system 900 in orophraynx 106 and larynx 107. In some embodiments, the laryngeal delivery system 900 comprise (a) a laryngeal delivery component such as an endotracheal tube 901 that is hollow and is delivered to the larynx 107 through the standard process of intubation via direct laryngoscopy and will thus allow for placement of the accompanying electrodes 306 at the target location (e.g., the larynx 107); (b) electrodes 306 present on or near the distal tip of the laryngeal delivery device 900 proximal to a cuff balloon 902 of the endotracheal tube 901 (if it has one) with various modifications and optimizations mentioned in the embodiments below, (c) a casing 903 having a housing that remains external to the patient and connected to the electrodes 306 via leads 904, and provides a base for the power button 304 (or other mechanism of activation) and light-based stimulation status indicator 305 and contains the electronic circuitry and power source for the stimulator and device 900, (d) power button 304 which is used to initiate and terminate the stimulation protocol, (e) stimulation status indicator 305 (which is light-based as described herein) will indicate whether the device 900 is on or off, and the progress of the stimulation protocol; and (f) leads 904 that will connect the electronics within the casing 903 to the electrodes 306.

Example 8: Laryngeal Delivery Device as Shown in FIG. 10

[0159] An exemplary embodiment of the laryngeal delivery device 900, shown in FIG. 10, comprises (a) a laryngeal delivery component such as an endotracheal tube 901 that is hollow and is delivered to the larynx 107 through the standard process of intubation via direct laryngoscopy and thus allow for placement of the accompanying electrodes 306 at the target location (e.g., the larynx 107); (b) electrodes 306 present on or near the distal tip of the laryngeal delivery device 900 proximal to the cuff balloon 902 (if it has one) of the endotracheal tube 901 that is embodied as wire(s) or other conductive elements of circular, flat, or other cross-section, that run along the outside or within the walls of the delivery device 900, affixed to the delivery device 900 to avoid dislodgement and placed on slightly angled diametrically opposite sides on the delivery device 900 so as to ensure sustained contact with the larynx 107 when endotracheal tube 901 is placed endotracheally; and (d) casing including parts (c)-(f) (housing, power button, stimulation status indicator, leads) described in Example 7.

Example 9: Laryngeal Delivery Device as Shown in FIG. 11

[0160] An exemplary embodiment of the laryngeal delivery device 900, shown in FIG. 11, comprises (a) a laryngeal delivery component such as an endotracheal tube 901 that is hollow and is delivered to the larynx 107 through the standard process of intubation via direct laryngoscopy and will thus allow for placement of the accompanying electrodes 306 at the target location (e.g., the larynx 107); (b) electrodes 306 that take the form of a circumferential conductive coating 307 present on or near the distal tip of the laryngeal delivery device 900 proximal to the cuff balloon 902 of the endotracheal tube 901 (if it has one) and is affixed to the delivery device 900 to avoid dislodgement or may be carried on a sliding member (e.g., a tube delivered coaxially over the endotracheal tube 901) and moved into place after intubation, ensuring sustained contact with the larynx 107 when placed endotracheally; and (c) a casing including parts (c)-(f) (housing, power button, stimulation status indicator, leads) as described in Example 7.

Example 10: Laryngeal Delivery Device as Shown in FIG. 12

[0161] An exemplary embodiment of the laryngeal delivery device 900, shown in FIG. 12, comprises (a) a laryngeal delivery component such as an endotracheal tube 901 that is hollow and is delivered to the larynx 107 through the standard process of intubation via direct laryngoscopy and will thus allow for placement of the accompanying electrodes 306 at the target location (e.g., the larynx 107); (b) electrode(s) 306 affixed to or contained within the surface of a secondary balloon 1201 included on or near the distal end of the delivery device 900, proximal to the cuff balloon 902 of the endotracheal tube 901 (if it has one) that when placed during intubation ensures sustained contact with the larynx 107 when placed endotracheally; this secondary balloon 1201 can be inflated through external injection of liquid or gaseous material; and (c) a casing including parts (c)-(f) (housing, power button, stimulation status indicator, leads) described in Example 7. Example 11: Laryngeal Delivery Device and System as Shown in FIG. 13A-FIG. 13B

[0162] An exemplary embodiment of the laryngeal delivery device and system are shown in FIG. 13A-FIG. 13B. As shown in FIG.13 A, the described device 900 is not pre-integrated with a laryngeal delivery component 901. FIG. 13 A illustrates a laryngeal delivery device 900 comprising electrodes 306 and leads 904. FIG. 13B illustrates a laryngeal delivery system 1300 comprising the laryngeal delivery device 900 and an endotracheal tube (ETT) 901. In some embodiments, the electrodes(s) 306 are separately pre-packaged from the rest of the components of the laryngeal delivery system. In some embodiments, the laryngeal delivery system 1300 comprises (a) a laryngeal delivery component such as an endotracheal tube 901 that is hollow and is delivered to the larynx 107 through the standard process of intubation via direct laryngoscopy and will thus allow for placement of the accompanying electrodes 306 at the target location (e.g., the larynx 107); (b) electrode(s) 306 that come pre-packaged on a flexible carrier designed to be wrapped around and adhesively or mechanically affixed to the distal end of the delivery device 901, proximal to the cuff balloon 902 of the endotracheal tube 901 (if it has one) that when placed during intubation ensures sustained contact with the larynx 107 when placed endotracheally; and (c) a casing including parts (c)-(f) (housing, power button, stimulation status indicator, leads) described in Example 7.

Example 12: Auricular Approach

[0163] In one embodiment, the device (e.g., device 300 described herein) is fully integrated and easily fit and stay in place in the right or left external ear of a human or other mammal, and does not require operator intervention to keep the device in place for the duration of action. The device will comprise several parts selected from: (a) a housing containing the internals (Internals will include (i) a battery or other source of power, (ii) a circuit designed to provide electrical stimulation, and (iii) an interface with the various external portions mentioned below) that is shaped and constituted of a material such that it maintains its position in the external ear, (b) an attachment to the housing that is adjustable and fits in a target location in the external ear, that can deliver the signal to the appropriate anatomical location innervated by a branch of the vagus nerve, such as the concha of the ear, including the cymba or the cavum, or other locations such as the tragus (c) one or more electrodes coupled to the aforementioned attachment that will deliver the electrical signal to the target nerve branch, with one such electrode potentially being utilized as an electrical ground, (d) a material providing conductive capabilities that is integrated into the presently disclosed devices or systems, one such embodiment being a hydrogel, to couple the electrodes to the skin in order to lessen resistance, (e) a post-like element that can be used to additionally house further electronic components, provide a base for other interface components, and be used to help position the device in the ear, (f) an interface element to control initiation and termination of stimulation that will additionally prevent the accidental initiation of stimulation, (g) a mechanism for indicating progress and status of initiation or termination of the stimulation process, as well as may include the capability of alerting the operator to any potential error conditions, embodiments of which may include visual or auditory cues including but not limited to means such as LED indicators or alert sounds, and (h) a method of mechanical fixation of the device that includes but is not limited to a tension-based or spring-loaded clip.

Example 13: Laryngeal Approach

[0164] The laryngeal delivery device (e.g., device 900 described herein) can be coupled with a laryngeal delivery component, e.g., an endotracheal tube (ETT). In some embodiments, the device comprises several components selected from: (a) one or more electrodes characterized by the following: (i) electrode(s) that are chemically, mechanically, electrically or magnetically coupled to a laryngeal delivery device; (ii) electrode(s) that are delivered directly on or in the laryngeal delivery device or on a carrier that could be fixed, expandable, and/or sliding; (ii) electrode(s) that are placed singly, doubly, or more; (iii) electrode(s) that are continuous or discontinuous, on either side of the laryngeal delivery device, or circumferentially, or toward the distal end, a length of 0-2 cm, or more, or along the entirety of the delivery device; (b) a casing that is external to the subject and comprises the following items: (i) a casing, (ii) a battery or other source of power and (iii) a circuit designed to provide electrical stimulation, (c) an interface button to control initiation and termination of stimulation that may additionally prevent the accidental initiation of stimulation, (d) a mechanism that indicates progress and status of initiation or termination of the stimulation process, as well as may include the capability of alerting the operator to any potential error conditions, embodiments of which include visual or auditory cues such as LED indicators or alert sounds, and (e) leads that connect the housing and/or associated circuitry to the electrodes, or alternatively an inductive coupling between housing/circuitry and electrodes.

Example 14: Process of Use— Auricular approach

[0165] The process will begin with preparing the skin surface to remove dirt and debris. The device will then be placed in the ear of the patient where it will rest self-sufficiently. In some embodiments, the device is anchored to the ear through an earplug or any other mechanism described herein. It will be turned on by the operator interfacing with the device. In some embodiments, the one or more electrodes of the device contact the cymba concha directly. In some embodiments, the electrodes of the device indirectly contact the cymba concha through the conductive material. Subsequent stimulation to the target portion of the ear will proceed without need for further operator intervention for a duration that is 5-10 minutes, or >10 minutes, or <5 minutes. After termination of stimulation, the device may be immediately removed from the ear, or may remain in the ear for some time, prior to being eventually removed.

Example 15: Process of Use— Laryngeal approach

[0166] The process will begin with placement of the laryngeal delivery system in the larynx; in one embodiment, this could involve endotracheal intubation with the laryngeal delivery system and concurrent or subsequent placement of the described electrodes in contact with the larynx. The electrodes will be coupled to the housing (that may be external to the subject) and the described device turned on by the operator interfacing with the device. Subsequent stimulation of the larynx will proceed without need for further operator intervention for a duration that is 5-10 minutes, or >10 minutes, or <5 minutes. After termination of stimulation, the casing and/or housing may be immediately decoupled from the electrodes, or may remain coupled for some time, prior to being eventually removed.

Example 16: Auricular Delivery Device as Shown in FIG. 14

[0167] An exemplary embodiment of the auricular delivery device 300, shown in FIG. 14, comprises (a) a housing 302 that comprises an anchoring mechanism 1402 (e.g., an earplug-like protrusion), (b) an attachment 301 that comprises electrodes 306 and a cymba concha contacting component 1403, (c) a mechanism of activation 1404, and (d) a combined contact alert indicator 1401 and stimulation status indicator 305. As shown in FIG. 14, in some embodiments, the anchoring mechanism 1402 is configured to fit into, or at least fit partially into, the subject’s ear canal. As shown in FIG. 14, in some embodiments, the attachment 301 has a curved shape. As shown in FIG. 14, in some embodiments, the device 300 comprises a contact alert indicator 1401 that indicates the status of electrodes 306-skin contact. In some embodiments, the signal displayed by the contact alert indicator 1401 indicating good electrodes-skin contact is different from the signal displayed indicating poor electrodes-skin contact. In some embodiments, the contact alert indicator 1401 is turned on when the electrodes-skin contact is good. In some embodiments, the contact alert indicator 1401 is turned on when the electrodes-skin contact is poor. As shown in FIG. 14, in some embodiments, the device 300 comprises a stimulation status indicator 305 that indicates, for example, whether the device 300 is on or off and/or the progress of the stimulation. In some embodiments, the contact alert indicator 1401 and the stimulation status indicator 305 are combined. For example, as shown in FIG. 14, the contact alert indicator 1401 and the stimulation status indicator 305 are integrated into one LED. The structure can be mirrored for the left ear, respectively. Example 17: Auricular Delivery Device as Shown in FIG. 15

[0168] An exemplary embodiment of the auricular delivery device 300, shown in FIG. 15, comprises (a) a housing 302 that comprises an anchoring mechanism 1402, (b) an attachment 301 that comprises electrodes 306 and a cymba concha contacting component 1403, (c) a mechanism of activation 1404, (d) a contact alert indicator 1401, and (e) a stimulation status indicator 305.

As shown in FIG. 15, in some embodiments, the anchoring mechanism 1402 is configured to fit into, or at least fit partially into, the subject’s ear canal. As shown in FIG. 15, in some embodiments, the attachment 301 has a curved shape. As shown in FIG. 15, in some

embodiments, the device 300 comprises a contact alert indicator 1401 that indicates the status of electrode 306-skin contact. As shown in FIG. 15, in some embodiments, the device 300 comprises a stimulation status indicator 305 that indicates, for example, whether the device 300 is on or off and the progress of the stimulation. As shown in FIG. 15, in some embodiments, the contact alert indicator 1401 and the stimulation status indicator 305 are separate. For example, as shown in FIG. 15, the contact alert indicator 1401 and the stimulation status indicator 305 are located at different positions of the housing 302. The structure can be mirrored for the left ear, respectively.

Example 18: Auricular Delivery Device as Shown in FIG. 16

[0169] FIG. 16 illustrates the back view of an exemplary embodiment of the auricular device 300, such as the embodiments of FIG. 14 or FIG. 15. As shown in FIG. 16, in some

embodiments, the described device 300 comprises (a) a housing 302 that comprises an anchoring mechanism 1402, (b) an attachment 301 that comprises electrodes 306 and a cymba concha contacting component 1403, and (c) a mechanism of activation 1404. As shown in FIG. 16, in some embodiments, the anchoring mechanism 1402 is configured to fit into, or at least fit partially into, the subject’s ear canal. As shown in FIG. 16, in some embodiments, the attachment 301 has a curved shape. As shown in FIG. 16, in some embodiments, the mechanism of activation 1404 is located on the side of the housing 302. In some embodiments, the device 300 of FIG. 16 comprises a contact alert indicator 1401, which is not shown. In some embodiments, the device 300 of FIG. 16 comprises a stimulation status indicator 305, which is not shown. In some embodiments, the device 300 of FIG. 16 comprises a combined contact alert indicator 1401 and stimulation status indicator 305, which is not shown. In some embodiments, the device 300 of FIG. 16 comprises a contact alert indicator 1401 and a stimulation status indicator 305, which are separate and not shown in FIG. 16. The structure can be mirrored for the left ear,

respectively. [0170] The examples and embodiments described herein are for illustrative purposes only and various modifications or changes suggested to persons skilled in the art are to be included within the spirit and purview of this application and scope of the appended claims. A person skilled in the art would appreciate that the embodiments and figures shown for the right ear can be mirrored and adapted to the left ear. In some embodiments, the described auricular delivery device comprises a device positioned in the right ear and a device positioned in the left ear.

[0171] While preferred embodiments of the subject matter disclosed herein have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. It is not intended that the invention be limited by the specific examples provided within the specification. While the invention has been described with reference to the aforementioned specification, the descriptions and illustrations of the embodiments herein are not meant to be construed in a limiting sense. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the subject matter disclosed herein. Furthermore, it shall be understood that all aspects of the invention are not limited to the specific depictions, configurations, or relative proportions set forth herein which depend upon a variety of conditions and variables. It should be understood that various alternatives to the embodiments of the subject matter disclosed herein may be employed in practicing the subject matter disclosed herein. It is therefore contemplated that the invention shall also cover any such alternatives, modifications, variations, or equivalents. It is intended that the following claims define the scope of the subject matter disclosed herein and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims

CLAIMS WHAT IS CLAIMED IS:

1. A device for modulating a vagus nerve in an individual in need thereof, the device comprising:

a) a housing, wherein the housing is configured to anchor the device on or near an external ear of the individual;

b) an attachment coupled to the housing, the attachment comprising:

i. one or more electrodes, wherein the one or more electrodes are

configured to deliver an electrical stimulation to an auricular branch of the vagus nerve, and

ii. a conductive material located at a skin-side surface of the attachment, wherein the attachment is configured to contact a skin of a cymba concha of the external ear with the conductive material when the housing is anchored;

c) a power source disposed within the housing, wherein the power source is configured to provide at most 8 hours of the electrical stimulation;

d) an electrical circuit disposed within the housing, coupled to the one or more electrodes, and configured with a fixed setting for the electrical stimulation; e) a mechanism of activation coupled to the housing and operably coupled to the power source and the electrical circuit, wherein the mechanism of activation is configured to activate the electrical stimulation; and

f) a stimulation status indicator coupled to the housing, wherein the stimulation status indicator indicates an on status, a progress of the electrical stimulation, or both.

2. The device of claim 1, wherein the housing is configured to fit in and maintain its position in a concha cavum of the individual, thereby anchoring the device in the external ear of the individual.

3. The device of claim 2, wherein the housing comprises a pliable material configured to conform to the concha cavum when inserted therein.

4. The device of claim 1, wherein the housing is configured to maintain a position behind the external ear, thereby anchoring the device near the external ear of the individual.

5. The device of claim 4, wherein the housing and the attachment are connected to one another by an over-the-ear hook component.

6. The device of claim 1, wherein the housing comprises an earplug configured to fit in an ear canal of the individual.

7. The device of claim 6, wherein the earplug is configured to fit in an external portion of the individual’s ear canal.

8. The device of claim 6 or 7, wherein the earplug comprises a pliable material that conforms to the ear canal when inserted therein.

9. The device of claim 6 or 7, wherein the earplug is flanged.

10. The device of any one of claims 1 to 9, wherein the housing is shaped as an ergonomic handle and configured to set or manipulate an initial position of the device within the external ear.

11. The device of any one of claims 1 to 10, wherein the housing comprises an attached clip that is configured to anchor the device over the external ear.

12. The device of any one of claims 1 to 11, wherein the stimulation status indicator is disposed on a side of the housing or on a surface of the housing that is opposite to the skin-side surface.

13. The device of any one of claims 1 to 12, wherein the housing further comprises a post.

14. The device of claim 13, wherein the post and the attachment are connected to the housing on opposite sides of the housing.

15. The device of claim 13 or 14, wherein the electrical circuit, the power source, the power button, the stimulation status indicator, or a combination thereof is disposed on or within the post.

16. The device of any one of claims 13 to 15, wherein the post is shaped as an ergonomic handle and configured to set or manipulate an initial position of the device within the external ear.

17. The device of any one of claims 1 to 16, wherein the attachment is configured to maintain the contact between the conductive material and the skin in the individual’s cymba concha when the device is anchored on or near the external ear of the individual.

18. The device of any one of claims 1 to 17, wherein the attachment is semi-flexible.

19. The device of any one of claims 1 to 18, wherein the attachment has a curved shape.

20. The device of claim 19, wherein the attachment is curved toward a cheek of the individual.

21. The device of any one of claims 1 to 18, wherein the attachment has a straight shape.

22. The device of any one of claims 1 to 21, wherein the attachment comprises a pliable material configured to conform to the ear when inserted therein.

23. The device of any one of claims 1 to 22, wherein the one or more electrodes comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20 or more electrodes disposed on or within the attachment.

24. The device of any one of claims 1 to 23, wherein at least one of the one or more electrodes has a shape of a loop, a cross, a bar, a dot, or a wire.

25. The device of any one of claims 1 to 20, wherein at least one of the one or more electrodes is a bar-shaped electrode.

26. The device of any one of claims 1 to 25, wherein at least one of the one or more electrodes is a dot-shaped electrode.

27. The device of any one of claims 1 to 26, wherein the attachment comprises a non- conductive material disposed on a surface of attachment that is opposite to the skin-side surface of the attachment.

28. The device of any one of claims 1 to 27, wherein the conductive material is placed between the skin and the one or more electrodes.

29. The device of any one of claims 1 to 28, wherein the conductive material at least partially covers the one or more electrodes on the skin-side surface.

30. The device of any one of claims 1 to 22, wherein the attachment is an electrode.

31. The device of claim 30, wherein the attachment consists essentially of the conductive material.

32. The device of claim 30 or 31, wherein the attachment is made of the conductive material.

33. The device of any one of claims 1 to 32, wherein the conductive material comprises a conductive gel, a conductive polymer, a conductive liquid selected from water, ionic liquid and alcohol, metal, an alloy, carbon black, or a combination thereof.

34. The device of any one of claims 1 to 33, wherein the conductive material comprises a hydrogel.

35. The device of any one of claims 1 to 33, wherein the conductive material comprises a conductive silicone.

36. The device of any one of claims 1 to 35, wherein the fixed setting sets the electrical stimulation at a frequency of at least 0.1 Hz, at least 1 Hz, at least 2 Hz, at least 3 Hz, at least 4 Hz, at least 5 Hz, at least 6 Hz, at least 7 Hz, at least 8 Hz, at least 9 Hz, at least 10 Hz, at least 11 Hz, at least 12 Hz, at least 13 Hz, at least 14 Hz, at least 15 Hz, at least 16 Hz, at least 17 Hz, at least 18 Hz, at least 19 Hz, at least 20 Hz, at least 21 Hz, at least 22 Hz, at least 23 Hz, at least 24 Hz, at least 25 Hz, at least 26 Hz, at least 27 Hz, at least 28 Hz, at least 29 Hz, at least 30 Hz, at least 40 Hz, or at least 50 Hz.

37. The device of any one of claims 1 to 35 wherein the fixed setting sets the electrical stimulation at a frequency of at most 5 Hz, at most 6 Hz, at most 7 Hz, at most 8 Hz, at most 9 Hz, at most 10 Hz, at most 11 Hz, at most 12 Hz, at most 13 Hz, at most 14 Hz, at most 15 Hz, at most 16 Hz, at most 17 Hz, at most 18 Hz, at most 19 Hz, at most 20 Hz, at most 21 Hz, at most 22 Hz, at most 23 Hz, at most 24 Hz, at most 25 Hz, at most 26 Hz, at most 27 Hz, at most 28 Hz, at most 29 Hz, at most 30 Hz, at most 35 Hz, at most 40 Hz, at most 45 Hz, at most 50 Hz, at most 60 Hz, at most 70 Hz, at most 80 Hz, at most 90 Hz, or at most 100 Hz.

38. The device of any one of claims 1 to 37, wherein the fixed setting sets the electrical stimulation at a frequency of from about 5 Hz to about 60 Hz.

39. The device of any one of claims 1 to 37, wherein the fixed setting sets the electrical stimulation at a frequency of about 25 Hz.

40. The device of any one of claims 1 to 39, wherein the fixed setting comprises a plurality of frequencies of from 0.1 Hz to 100 Hz for the electrical stimulation.

41. The device of any one of claims 1 to 39, wherein the fixed setting comprises a frequency of about 0.1 Hz, about 1 Hz, about 2 Hz, about 3 Hz, about 4 Hz, about 5 Hz, about 6 Hz, about 7 Hz, about 8 Hz, about 9 Hz, about 10 Hz, about 11 Hz, about 12 Hz, about 13 Hz, about 14 Hz, about 15 Hz, about 16 Hz, about 17 Hz, about 18 Hz, about 19 Hz, about 20 Hz, about 21 Hz, about 22 Hz, about 23 Hz, about 24 Hz, about 25 Hz, about 26 Hz, about 27 Hz, about 28 Hz, about 29 Hz, about 30 Hz, about 35 Hz, about 40 Hz, about 45 Hz, about 50 Hz, about 60 Hz, about 70 Hz, about 80 Hz, about 90 Hz, or about 100 Hz for the electrical stimulation.

42. The device of any one of claims 1 to 41, wherein the fixed setting sets the electrical stimulation at a pulse width of at least 1 ps, at least 10 ps, at least 50 ps, at least 100 ps, at least 150 ps, at least 200 ps, at least 250 ps, at least 300 ps, at least 350 ps, at least 400 ps, at least 450 ps, or at least 500 ps.

43. The device of any one of claims 1 to 41, wherein the fixed setting sets the electrical stimulation at a pulse width of at most 100 ps, at most 150 ps, at most 200 ps, at most 250 ps, at most 300 ps, at most 350 ps, at most 400 ps, at most 500 ps, at most 600 ps, at most 700 ps, at most 800 ps, at most 900 ps, at most 1000 ps, at most 1500 ps, or at most 2000 ps.

44. The device of any one of claims 1 to 41, wherein the fixed setting sets the electrical stimulation at a pulse width of from about 100 ps to about 2000 ps.

45. The device of any one of claims 1 to 41, wherein the fixed setting sets the electrical stimulation at a pulse width of about 250 ps.

46. The device of any one of claims 1 to 41, wherein the fixed setting comprises a plurality of pulse widths of from 1 ps to 2000 ps for the electrical stimulation.

47. The device of any one of claims 1 to 41, wherein the fixed setting comprises a pulse width of about 1 ps, about 10 ps, about 50 ps, about 100 ps, about 150 ps, about 200 ps, about 210 ps, about 220 ps, about 230 ps, about 240 ps, about 250 ps, about 260 ps, about 270 ps, about 280 ps, about 290 ps, about 300 ps, about 350 ps, about 400 ps, about 450 ps, about 500 ps, about 600 ps, about 700 ps, about 800 ps, about 900 ps, or about 1000 ps for the electrical stimulation.

48. The device of any one of claims 1 to 47, wherein the fixed setting sets the electrical stimulation at a current passing through one of the one or more electrodes of at least 0.01 mA, at least 0.1 mA, at least 1 mA, at least 2 mA, at least 3 mA, at least 4 mA, at least 5 mA, at least 6 mA, at least 7 mA, at least 8 mA, at least 9 mA, at least 10 mA, at least 11 mA, at least 12 mA, at least 13 mA, at least 14 mA, at least 15 mA, at least 16 mA, at least 17 mA, at least 18 mA, at least 19 mA, at least 20 mA, at least 21 mA, at least 22 mA, at least 23 mA, at least 24 mA, at least 25 mA, at least 26 mA, at least 27 mA, at least 28 mA, at least 29 mA, at least 30 mA, at least 40 mA, or at least 50 mA.

49. The device of any one of claims 1 to 47, wherein the fixed setting sets the electrical stimulation at a current passing through one of the one or more electrodes of at most 1 mA, at most 5 mA, at most 6 mA, at most 7 mA, at most 8 mA, at most 9 mA, at most 10 mA, at most

11 mA, at most 12 mA, at most 13 mA, at most 14 mA, at most 15 mA, at most 16 mA, at most

17 mA, at most 18 mA, at most 19 mA, at most 20 mA, at most 25 mA, at most 30 mA, at most

35 mA, at most 40 mA, at most 45 mA, at most 50 mA, at most 60 mA, at most 70 mA, at most

80 mA, at most 90 mA, or at most 100 mA.

50. The device of any one of claims 1 to 47, wherein the fixed setting sets the electrical stimulation at a current passing through one of the one or more electrodes of from about 0.1 mA to 60 mA.

51. The device of any one of claims 1 to 47, wherein the fixed setting sets the electrical stimulation at a current passing through one of the one or more electrodes of about 10 mA.

52. The device of any one of claims 1 to 47, wherein the fixed setting comprises a plurality of currents of from 0.01 mA to 100 mA for the electrical stimulation.

53. The device of any one of claims 1 to 47, wherein the fixed setting comprises a current of about 0.1 mA, about 1 mA, about 2 mA, about 3 mA, about 4 mA, about 5 mA, about 6 mA, about 7 mA, about 8 mA, about 9 mA, about 10 mA, about 11 mA, about 12 mA, about 13 mA, about 14 mA, about 15 mA, about 16 mA, about 17 mA, about 18 mA, about 19 mA, about 20 mA, about 21 mA, about 22 mA, about 23 mA, about 24 mA, about 25 mA, about 26 mA, about 27 mA, about 28 mA, about 29 mA, about 30 mA, about 40 mA, about 50 mA, about 60 mA, about 70 mA, about 80 mA, about 90 mA, or about 100 mA for the electrical stimulation.

54. The device of any one of claims 1 to 47, wherein the fixed setting comprises a current of about 10 mA for the electrical stimulation.

55. The device of any one of claims 1 to 54, wherein the power source provides a voltage of at least 0.5 V, at least 1 V, at least 5 V, at least 10 V, at least 11 V, at least 12 V, at least 13 V, at least 14 V, at least 15 V, at least 16 V, at least 17 V, at least 18 V, at least 19 V, at least 20 V, at least 21 V, at least 22 V, at least 23 V, at least 24 V, at least 25 V, at least 26 V, at least 27 V, at least 28 V, at least 29 V, at least 30 V, at least 40 V, or at least 50 V.

56. The device of any one of claims 1 to 55, wherein the power source provides a voltage of at most 1 V, at most 5 V, at most 6 V, at most 7 V, at most 8 V, at most 9 V, at most 10 V, at most 11 V, at most 12 V, at most 13 V, at most 14 V, at most 15 V, at most 16 V, at most 17 V, at most 18 V, at most 19 V, at most 20 V, at most 25 V, at most 30 V, at most 35 V, at most 40 V, at most 45 V, at most 50 V, at most 60 V, at most 70 V, at most 80 V, at most 90 V, or at most 100 V.

57. The device of any one of claims 1 to 55, wherein the power source provides a voltage of from about 5 V to about 60 V.

58. The device of any one of claims 1 to 55, wherein the power source provides a voltage of about 24V.

59. The device of any one of claims 1 to 55, wherein the fixed setting comprises a plurality of voltages of from 0.1 V to 100 V.

60. The device of any one of claims 1 to 59, wherein the power source is configured to provide at most 2 minutes, at most 5 minutes, at most 10 minutes, at most 30 minutes, at most 1 hour, at most 2 hours, at most 4 hours, or at most 7 hours of electrical stimulation.

61. The device of any one of claims 1 to 59, wherein the power source is configured to provide at least 10 seconds, at least 30 seconds, at least 1 minute, at least 2 minutes, at least 5 minutes, at least 10 minutes, at least 30 minutes, at least 1 hour, or at least 2 hours of electrical stimulation.

62. The device of any one of claims 1 to 59, wherein the power source is configured to provide from about 2 minutes to about 15 minutes of electrical stimulation.

63. The device of any one of claims 1 to 59, wherein the power source is configured to provide about 5 minutes of electrical stimulation.

64. The device of any one of claims 1 to 63, wherein the power source comprises one or more batteries.

65. The device of claim 64, wherein each of the batteries has a capacity of at least 1 mAh, at least 10 mAh, at least 25 mAh, at least 50 mAh, at least 75 mAh, at least 100 mAh, at least 125 mAh, at least 150 mAh, or at least 170 mAh.

66. The device of claim 64 or 65, wherein each of the batteries has a capacity of at most 50 mAh, at most 100 mAh, at most 150 mAh, at most 200 mAh, at most 300 mAh, or at most 500 mAh.

67. The device of any one of claims 64 to 66, wherein each of the batteries has a capacity of from about 10 mAh to about 200 mAh.

68. The device of any one of claims 64 to 67, wherein at least one of the batteries has a capacity of about 170 mAh.

69. The device of any one of claims 64 to 68, wherein each of the batteries provides a voltage of at least 0.5 V, at least 1 V, at least 1.5 V, at least 2 V, at least 2.5 V, at least 3 V, at least 4 V, at least 5 V, at least 6 V, at least 7 V, at least 8 V, or at least 9 V.

70. The device of any one of claims 64 to 69, wherein each of the batteries provides a voltage of at most 5 V, at most 6 V, at most 7 V, at most 8 V, at most 9 V, at most 10 V, at most 11 V, at most 12 V, at most 13 V, at most 14 V, or at most 15 V.

71. The device of any one of claims 64 to 70, wherein each of the batteries provides a voltage of from 1.5 V to 9 V.

72. The device of any one of claims 64 to 71, wherein at least one of the batteries provides a voltage of about 5 V.

73. The device of any one of claims 64 to 72, wherein the batteries are rechargeable.

74. The device of any one of claims 64 to 72, wherein the batteries are non-rechargeable.

75. The device of any one of claims 64 to 74, wherein the batteries comprise silver-oxide batteries, alkaline batteries, lithium-ion batteries, zinc-carbon batteries, nickel -cadmium batteries, nickel metal hydride batteries, or a combination thereof.

76. The device of any one of claims 64 to 74, wherein the batteries are silver-oxide batteries.

77. The device of any one of claims 1 to 76, wherein the electrical stimulation has a waveform.

78. The device of claim 77, wherein the waveform is shaped.

79. The device of claim 77, wherein the waveform is sinusoidal, square, sawtooth, or triangular.

80. The device of any one of claims 1 to 79, wherein the fixed setting comprises a plurality of waveforms for the electrical stimulation.

81. The device of claim 80, wherein the fixed setting comprises a waveform that is sinusoidal, square, triangular, or sawtooth for the electrical stimulation.

82. The device of any one of claims 1 to 81, wherein the mechanism of activation comprises a power button.

83. The device of claim 82, wherein the power button toggles the electrical stimulation between an on status and an off status.

84. The device of claim 82 or 83, wherein the electrical stimulation is activated by pressing the power button.

85. The device of claim 82 or 83, wherein the electrical stimulation is activated by sliding the power button.

86. The device of claim 82, wherein the power button is not configured to turn off the electrical stimulation.

87. The device of any one of claims 1 to 81, wherein the mechanism of activation comprises pull tab activation.

88. The device of any one of claims 1 to 82 or 84 to 87, wherein the mechanism of activation is incapable of deactivating the electrical stimulation.

89. The device of any one of claims 1 to 88, wherein the mechanism of activation and the stimulation status indicator are separated.

90. The device of any one of claims 1 to 88, wherein the mechanism of activation and the stimulation status indicator are combined.

91. The device of any one of claims 1 to 90, wherein the stimulation status indicator indicates the off status.

92. The device of claim 91, wherein the off status is an affirmative signal comprising light, sound, or both.

93. The device of claim 91, wherein the off status is the lack of an affirmative signal.

94. The device of any one of claims 1 to 93, wherein the stimulation status indicator is light-based.

95. The device of any one of claims 1 to 94, wherein the stimulation status indicator comprises a light-emitting diode (LED).

96. The device of any one of claims 1 to 95, wherein the device comprises a contact alert indicator that indicates a good electrode-skin contact, a poor electrode-skin contact, or both.

97. The device of claim 96, wherein the contact alert indicator is located on a surface of the housing that is opposite to the skin side.

98. The device of claim 96 or 97, wherein the contact alert indicator is light-based.

99. The device of claim 98, wherein the contact alert indicator comprises an LED.

100. The device of claim 96 or 97, wherein the contact alert indicator is sound-based.

101. The device of any one of claims 96 to 100, wherein a good electrode-skin contact is an affirmative signal comprising light, sound, or both.

102. The device of any one of claims 96 to 101, wherein a poor electrode-skin contact is an affirmative signal or a lack of an affirmative signal.

103. The device of any one of claims 96 to 100, wherein a good electrode-skin contact is a lack of an affirmative signal.

104. The device of any one of claims 96 to 100 or 103, wherein a poor electrode-skin contact is an affirmative signal.

105. The device of any one of claims 96 to 104, wherein the stimulation status indicator and the contact alert indicator are combined.

106. The device of claim 105, wherein the stimulation status indicator and the contact alert indicator are integrated into one LED.

107. The device of any one of claims 96 to 104, wherein the stimulation status indicator and the contact alert indicator are separate.

108. The device of any one of claims 1 to 107, wherein the device is configured for a single use.

109. The device of any one of claims 1 to 108, wherein the electrical stimulation is predetermined or pre-programmed.

110. A method of stimulating a vagus nerve of an individual in need thereof, the method comprising:

a) positioning the device in any one of claims 1 to 109 on or near the external ear of the individual, thereby placing the one or more electrodes on the individual’s cymba concha and contacting the conductive material to the cymba concha; and

b) initiating the electrical stimulation through the mechanism of activation.

111. A method of preventing ileus in an individual in need thereof, comprising

(i) positioning the device in any one of claims 1 to 109 on or near the external ear of the individual,

(ii) initiating an electrical stimulation of a vagus nerve of an individual, wherein the electrical stimulation comprises a fixed setting comprising one or more frequencies of from 5 Hz to 60 Hz, one or more pulse widths of from 100 ps to 2000 ps, and one or more currents of from 0.01 mA to 60 mA, wherein the fixed setting is configured to stimulate C fibers without stimulating A or B fibers of the vagus nerve;

(iii) stimulating a C fiber of the vagus nerve for no more than 1 hour, thereby preventing ileus; and

(iv) ending the electrical stimulation.

112. A method of stimulating a vagus nerve of an individual in need thereof, the method comprising:

a) positioning a device on or near an external ear of the individual, wherein the device comprises:

i. an attachment configured to attach to a housing or an earbud, the

attachment comprising:

1) one or more electrodes configured to deliver electrical

stimulation, and

2) a conductive material located at a skin-side surface of the

attachment;

ii. a power source configured to provide at most 8 hours of electrical stimulation;

b) placing the one or more electrodes on or near a cymba concha of the

individual, thereby creating a contact between the skin-side surface of the attachment and the cymba concha; and

c) initiating the electrical stimulation through a mechanism of activation, wherein the electrical stimulation stimulates C fibers of the vagus nerve.

113. The method of claim 112, wherein the attachment is integrated with or configured to attach to a housing, and wherein the housing is configured to anchor the device on or near the external ear.

114. The method of claim 112, wherein the attachment is configured to attach to an earbud.

115. The method of any one of claims 112 to 114, wherein the attachment is configured as a sleeve.

116. A method of stimulating a vagus nerve of an individual in need thereof, the method comprising:

i. a housing, wherein the housing is configured to anchor the device on or near the external ear;

ii. an attachment coupled to the housing, the attachment comprising:

1) one or more electrodes configured to deliver electrical

stimulation, and

2) a conductive material located at a skin-side surface of the

attachment; iii. a power source disposed within the housing, wherein the power

source is configured to provide at most 8 hours of electrical stimulation;

b) placing the one or more electrodes on or near a cymba concha of the

c) initiating the electrical stimulation through a mechanism of activation

operably coupled to the power source, wherein the electrical stimulation stimulates C fibers of the vagus nerve.

117. The method of any one of claims 110 to 116, wherein the electrical stimulation do not create any vibrotactile effects.

118. The method of any one of claims 110 to 117, wherein the electrical stimulation stimulates A fibers of the vagus nerve, B fibers of the vagus nerve, or both.

119. The method of any one of claims 110 to 118, wherein the electrical stimulation is initiated during an abdominal surgery procedure performed on the individual or before the individual receives an abdominal surgery procedure.

120. The method of claim 119, wherein the electrical stimulation is initiated at least 1 minute, at least 5 minutes, at least 10 minutes, at least 30 minutes, at least 1 hour, at least 2 hours, or at least 4 hours before the abdominal surgery procedure.

121. The method of claim 119, wherein the electrical stimulation is initiated at most 1 minute, at most 5 minutes, at most 10 minutes, at most 30 minutes, at most 1 hour, at most 2 hours, at most 4 hours, or at most 8 hours before the abdominal surgery procedure.

122. The method of any one of claims 110 to 121, wherein the electrical stimulation is initiated by turning on the power button.

123. The method of any one of claims 110 to 122, further comprising terminating the electrical stimulation.

124. The method of claim 123, wherein the electrical stimulation is terminated through the mechanism of activation.

125. The method of claim 123, wherein the electrical stimulation is terminated by exhausting the power source.

126. The method of any one of claims 110 to 125, further comprising initiating a second electrical stimulation.

127. A method of initiating a fixed setting of electrical stimulation delivered by a device, the method comprising: a) initiating an electrical stimulation having a fixed setting with a device,

wherein the device comprises:

a. a housing configured to anchor the device on or near an external ear; b. an attachment coupled to the housing, the attachment comprising: i. one or more electrodes, wherein the one or more electrodes are

configured to deliver the fixed setting of electrical stimulation, and ii. a conductive material located at the skin-side surface of the

attachment,

wherein the fixed setting comprises one or more frequencies within a range from 0.1 Hz to 100 Hz, one or more pulse widths within a range from 1 ps to 2000 ps, and one or more currents within a range from 0.01 mA to 100 mA, and

wherein the electrical stimulation stimulates the C fibers of the vagus nerve.

128. The method of claim 127, wherein the method comprises toggling the power button to an on status.

129. The method of claim 127 or 128, wherein the fixed setting comprises a frequency of about 25 Hz, a pulse width of about 250 ps, and a current of about 10 mA.

130. The method of any one of claims 127 to 129, wherein the electrical stimulation is effective in preventing ileus.

131. A device for modulating a vagus nerve in an individual in need thereof, the device comprising:

a) an electrode carrier comprising a first electrode, wherein the first electrode is configured to deliver an electrical stimulation to a laryngeal branch of a vagus nerve of an individual;

b) a casing configured to be disposed outside a body of the individual when the first electrode is placed adjacent to a larynx of the individual, wherein the casing comprises

i. a housing;

ii. a mechanism of activation configured to initiate the electrical

stimulation,

iii. a stimulation status indicator coupled to the housing, wherein the stimulation status indicator is configured to indicate an on status of the device, a progress of the electrical stimulation, or both,

iv. a power source disposed within the housing, wherein the power source is configured to provide at most 8 hours of the electrical stimulation, and v. an electrical circuit disposed within the housing, wherein the electrical circuit is operably coupled to the power source; and

c) one or more leads each comprising a proximal end and a distal end, wherein the proximal end is coupled to the electrical circuit and the distal end is coupled to the electrode.

132. The device of claim 131, wherein the electrode carrier is configured to attach to a laryngeal delivery component.

133. The device of claim 132, wherein the laryngeal delivery component is an endotracheal tube (ETT) that comprises a cuff balloon.

134. The device of any one of claims 131 to 133, wherein the device is configured to provide a fixed setting of electrical stimulation configured to stimulate A fibers, B fibers, C fibers of the vagus nerve, or a combination thereof.

135. The device of any one of claims 131 to 133, wherein the device is configured to provide a fixed setting of electrical stimulation configured to selectively stimulate C fibers of the vagus nerve.

136. The device of any one of claims 131 to 135, further comprising a second electrode configured to deliver the electrical stimulation to the laryngeal branch of the vagus nerve.

137. The device of claim 136, further comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, or more electrodes configured to deliver the electrical stimulation to the laryngeal branch of the vagus nerve.

138. The device of claim 137, wherein the electrode is configured to be placed proximal to the cuff balloon.

139. The device of any one of claims 131 to 138, wherein the electrode carrier is configured to attach to the laryngeal delivery component through thermal fastening, adhesives, or mechanical fastening.

140. The device of any one of claims 131 or 139, wherein the electrode carrier is configured to be removable from the laryngeal delivery component after attachment.

141. The device of any one of claims 131 to 140, wherein the electrode carrier is flexible.

142. The device of any one of claims 131 to 141, wherein the mechanism of activation comprises a power button or a pull tab activation.

143. The device of any one of claims 131 to 142, wherein the device comprises a contact alert indicator that indicates a good electrode-larynx contact, a poor electrode-larynx contact, or both.

144. The device of claim 143, wherein the contact alert indicator and the stimulation status indicator are combined.

145. The device of any one of claims 131 to 144, wherein the device is pre-integrated with the laryngeal delivery component.

146. A method of stimulating a vagus nerve of an individual in need thereof, the method comprising:

a) integrating the device in any one of claims 131 to 145 with a laryngeal

delivery component;

b) positioning the laryngeal delivery component in a larynx of the individual, thereby placing the first electrode in direct or indirect contact with the larynx; and

c) initiating the electrical stimulation through the mechanism of activation.

147. A method of stimulating a vagus nerve of an individual in need thereof, the method comprising:

a) positioning a laryngeal delivery component in a larynx of the individual; b) integrating the device in any one of claims 131 to 145 with the laryngeal delivery component, thereby placing the first electrode in direct or indirect contact with the larynx; and

c) initiating the electrical stimulation through the mechanism of activation.

148. The method of claim 146 or 147, wherein integrating comprises placing at least one of the electrodes on or near a distal end of the laryngeal delivery component.

149. The method of claim 148, wherein integrating comprises attaching the electrode carrier to the laryngeal delivery component.

150. A system for modulating a vagus nerve in an individual in need thereof, the system comprising:

a) a laryngeal delivery component comprising a proximal end, a distal end, a lumen extending therebetween, and a longitudinal axis extending from the proximal to the distal end;

b) an electrode carrier comprising a first electrode, wherein the first electrode is configured to deliver an electrical stimulation to a laryngeal branch of a vagus nerve of an individual, and wherein the electrode carrier is configured to attach to the laryngeal delivery component;

c) a casing configured to be disposed outside a body of the individual when the first electrode is placed adjacent to a larynx of the individual, wherein the casing comprises: i. a housing,

ii. a mechanism of activation coupled to the housing, wherein the

mechanism of activation is configured to initiate the electrical stimulation,

iii. a stimulation status indicator coupled to the housing, wherein the

stimulation status indicator is configured to indicate an on status of the device, a progress of the electrical stimulation, or both,

iv. a power source disposed within the housing, wherein the power source is configured to provide at most 8 hours of the electrical stimulation, and

v. an electrical circuit disposed within the housing, wherein the electrical circuit is operably coupled to the power source; and

d) one or more leads each comprising a proximal end and a distal end, wherein the proximal end is coupled to the electrical circuit and the distal end is coupled to the first electrode.

151. The system of claim 150, wherein the electrode carrier comprises 2, 3, 4, 5, 6, 7,

8, 9, 15, 20 or more electrodes.

152. The system of claim 150 or 151, wherein the laryngeal delivery component is an endotracheal tube (ETT).

153. The system of any one of claims 150 to 152, wherein the laryngeal delivery component comprises a cuff balloon.

154. The system of claim 153, wherein the electrode is placed proximal to the cuff balloon.

155. The system of claim 153, wherein cuff balloon is situated between the electrode and the distal end of the laryngeal delivery component.

156. The system of any one of claims 150 to 155, wherein the electrode is housed within the laryngeal delivery component.

157. The system of claim 156, wherein the electrode is positioned on an internal surface of the laryngeal delivery component.

158. The system of any one of claims 150 to 156, wherein the electrode is positioned on an external surface of the laryngeal delivery component.

159. The system of claim 158, wherein the electrode is configured to maintain a contact with the larynx.

160. The system of any one of claims 151 to 159, wherein at least two electrodes are positioned parallel to the longitudinal axis of the laryngeal delivery component.

161. The system of claim 160, wherein all electrodes are positioned parallel to the longitudinal axis of the laryngeal delivery component.

162. The system of any one of claims 151 to 159, wherein at least two electrodes are positioned in a pattern perpendicular to the longitudinal axis of the laryngeal delivery component.

163. The system of claim 162, wherein all electrodes are positioned in a pattern perpendicular to the longitudinal axis of the laryngeal delivery component.

164. The system of any one of claims 153 to 163, wherein the laryngeal delivery component comprises a secondary balloon near the distal end.

165. The system of claim 164, wherein the cuff balloon is situated between the secondary balloon and the distal end of the laryngeal delivery component.

166. The system of claim 164 or 165, wherein the electrodes are affixed to or contained within an external or internal surface of the secondary balloon.

167. The system of any one of claims 164 to 166, wherein a diameter of the secondary balloon is the same as or different from a diameter of the cuff balloon.

168. The system of any one of claims 164 to 167, wherein the secondary balloon is configured to maintain a contact with the larynx.

169. The system of any one of claims 164 to 168, wherein the secondary balloon is coated with a conductive material.

170. The system of any one of claims 150 to 169, wherein the first electrode is in a form of a circumferential conductive coating.

171. The system of any one of claims 150 to 169, wherein the first electrode has a cross-section that is circular, flat, rectangle, or square.

172. The system of any one of claims 150 to 169, wherein the first electrode has a shape that is a wire, a bar, a dot, a cross, or a loop.

173. The system of any one of claims 150 to 172, wherein the first electrode is disposed in an electrode carrier.

174. The system of any one of claims 150 to 173, wherein the electrode carrier is attached to the laryngeal delivery component through thermal fastening, adhesives, or

mechanical fastening.

175. The system of claim 174, wherein the electrode carrier is removable from the laryngeal delivery component.

176. The system of any one of claims 150 to 175, wherein the electrode carrier is flexible.

177. The system of any one of claims 150 to 176, wherein the electrode carrier comprises conductive material.

178. The system of claim 177, wherein the electrodes are at least partially covered by the conductive material at a side facing the larynx.

179. The system of any one of claims 150 to 178, wherein the system is pre-integrated.

180. The system of any one of claims 150 to 178, wherein the laryngeal delivery component is not pre-integrated in the system.

181. A method of stimulating a vagus nerve of an individual in need thereof, the method comprising:

a) positioning the system in any one of claims 150 to 180 in a larynx of the

individual, thereby placing at least one of the electrodes in direct or indirect contact with the larynx; and

b) initiating the electrical stimulation.

182. A method of initiating a fixed setting of electrical stimulation delivered by a device, the method comprising:

a) initiating an electrical stimulation at a fixed setting with a device, wherein the device comprises:

a. an electrode carrier comprising a first electrode;

b. a casing separate from but coupled to the electrode carrier, the casing comprising:

i. a housing,

ii. a mechanism of activation, wherein the mechanism of activation

operates the first electrode,

iii. a stimulation status indicator coupled to the housing, wherein the

stimulation status indicator indicates an on status of the device, the progress of an electrical stimulation by the first electrode, or both, iv. a power source disposed within the housing, wherein the power source is configured to provide at most 8 hours of the electrical stimulation, and

v. an electrical circuit disposed within the housing, wherein the electrical circuit is operably coupled to the power source and the first electrode; and

c. one or more leads each comprising a proximal end and a distal end,

wherein the proximal end is coupled to the electrical circuit and the distal end is coupled to the first electrode, and wherein the fixed setting comprises one or more frequencies of from 0.1 Hz to 100

Hz, one or more pulse widths of from 1 ps to 2000 ps, and one or more currents of from

0.01 mA to 100 mA.

183. The method of claim 182, wherein the housing is configured to be disposed outside the individual when the first electrode is placed adjacent to a larynx of the individual.

184. A method of generating a fixed setting of electrical stimulation, the method comprising:

a) turning on a power switch of a device thereby initiating the fixed setting for an electrical stimulation, wherein the device comprises:

a. a first electrode configured to output the electrical stimulation; and b. a casing coupled to the first electrode, the casing comprising:

i. a housing,

ii. the power switch configured to operate the first electrode at the fixed setting,

iii. a power source within the housing configured to provide at most 8 hours of the electrical stimulation, and

iv. an electrical circuit disposed within the housing, wherein the electrical circuit is operably coupled to the power source and the first electrode and defines the fixed setting of the electrical stimulation;

wherein the fixed setting comprises one or more frequencies of from 0.1 Hz to 100 Hz, one or more pulse widths of from 1 ps to 2000 ps, and one or more currents of from 0.01 mA to 100 mA.

185. The method of claim 184, wherein the device comprises a stimulation status indicator that indicates an on status of the device, the progress of an electrical stimulation by the first electrode, or both.

186. The method of claim 184 or 185, wherein the casing of the device is configured to removably or permanently attach to an endotracheal tube.

187. The method of any one of claims 181 - 186, wherein the device is configured to provide a fixed setting of electrical stimulation configured to stimulate the A, C, or C fibers of the vagus nerve.

188. The method of any one of claims 181 - 186, wherein the device is configured to provide a fixed setting of electrical stimulation configured to selectively stimulate C fibers of the vagus nerve without stimulating A and B fibers of the vagus nerve.

189. Use of a device according to any one of claims 1 to 108 or 131 to 144 or a system according to any one of claims 150 to 180, for modulating a vagus nerve of an individual by providing a fixed setting of electrical stimulation, wherein the fixed setting of electrical stimulation comprises one or more frequencies of from 0.1 Hz to 100 Hz, one or more pulse widths of from 1 ps to 2000 ps, and one or more currents of from 0.01 mA to 100 mA.

190. A device for use in a method of stimulating a vagus nerve of an individual in need thereof, wherein the device comprises:

a) an attachment comprising:

(i) one or more electrodes integrated to a body of the attachment, wherein the one or more electrodes are configured to deliver an electrical stimulation to an auricular branch of a vagus nerve, and

(ii) a conductive material located at a skin-side surface of the attachment, wherein the attachment is configured to allow the one or more electrodes or the conductive material to come into contact with a skin in a cymba concha of the individual when the device is positioned on or near an external ear of the individual; and

b) a mechanism of activation operably coupled to the one or more electrodes and configured to activate the electrical stimulation,

wherein, after the electrical stimulation is initiated through the mechanism of activation, the device is configured to provide a fixed setting of electrical stimulation configured to stimulate C fibers of the vagus nerve,

wherein the fixed setting comprises one or more frequencies within a range of 5 Hz to 60 Hz, one or more pulse widths within a range of 100 ps to 2000 ps, and one or more currents within a range of 0.01 mA to 60 mA.

191. The device of claim 190, wherein the device does not create any vibrotactile effect.

192. A device for use in a method of stimulating a vagus nerve of an individual in need thereof, wherein the device comprises:

(i) an electrode carrier comprising a first electrode, wherein the first electrode is configured to deliver an electrical stimulation to a laryngeal branch of a vagus nerve of an individual; and

(ii) a mechanism of activation configured to activate the electrical stimulation,

wherein, after the electrical stimulation is initiated through the mechanism of activation, the device is configured to provide a fixed setting of electrical stimulation configured to stimulate C fibers of the vagus nerve, wherein the fixed setting comprises one or more frequencies within a range of 5 Hz to 60 Hz, one or more pulse widths within a range of 100 ps to 2000 ps, and one or more currents within a range of 0.01 mA to 60 mA.

193. The device of any one of claims 190-192, wherein the device is configured to provide a fixed setting of electrical stimulation configured to stimulate the A, B, or C fibers of the vagus nerve.

194. The device of any one of claims 190-192, wherein the device is configured to provide a fixed setting of electrical stimulation configured to selectively stimulate C fibers of the vagus nerve without stimulating A and B fibers of the vagus nerve.