Pulsed field electroporation system and method

Abstract

The improved systems described herein can include an inflatable member equipped with one or more pulsed field electroporation (PFE) electrodes configured to induce a local and targeted PFE output at a target tissue (e.g., to temporarily expand the target tissue).

Description

[0001] Related applications

[0002] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 621,443, filed January 16, 2024, the contents of which are incorporated herein by reference in their entirety. Technical Field

[0003] This disclosure relates to pulsed field electroporation (PFE) and expansion systems and methods. Some systems and methods include minimally invasive, expandable instrument balloons and therapeutic PFE methods for eustachian tube (ET), paranasal sinus, cochlea, olfactory system, and other ear, nose, and pharynx (ENT) surgeries. Background Technology

[0004] The Eustachian tube is a narrow passage, about 1.5 inches long, that connects the middle ear and the nasopharynx at the back of the nose (for example, just above the palate in the upper pharyngeal region).

[0005] The Eustachian tube acts as a pressure equalization valve for the normally air-filled middle ear. When functioning normally, the Eustachian tube opens for less than a second in response to swallowing or yawning, approximately once every three minutes. This allows air to enter the middle ear to replace air absorbed by the inner lining (mucosa) or to balance pressure changes caused by elevation variations. Interference with this periodic opening and closing of the Eustachian tube can lead to hearing loss or other ear symptoms.

[0006] A blockage or obstruction of the Eustachian tube can sometimes lead to negative pressure in the middle ear, which can cause the eardrum to retract. In adults, this is often accompanied by ear discomfort, a feeling of fullness or pressure, and can lead to hearing loss and ringing in the ear (tinnitus). If the blockage persists, fluid may be drained from the mucous membrane of the middle ear, resulting in a condition called serous otitis media (fluid in the middle ear). This is more common in children.

[0007] The paranasal sinus system is a combination of four pairs of air-filled cavities. The maxillary sinuses (buccal sinuses) surround the nasal cavity, the frontal sinuses are above the eyes, the ethmoid sinuses are between the eyes, and the sphenoid sinuses are located in the sphenoid bone at the center of the skull base below the pituitary gland. The paranasal sinuses are lined with respiratory epithelium and connect to the nasal cavity through small openings called the sinus ostia. The paranasal sinuses contain secretory tissues that produce large amounts of mucus. This mucus typically flows from the sinuses through their respective ostia in a specific pattern.

[0008] The mucous membrane lining the paranasal sinuses can become inflamed. This inflammation is called sinusitis (or rhinitis-associated sinusitis) and can be caused by a variety of factors, such as bacteria, viruses, allergies, anatomical abnormalities, etc. If the mucous membrane at one of the sinus openings becomes inflamed, the passage may become blocked, trapping mucus. People with sinusitis may experience several symptoms or complications, such as headaches, facial pain, toothaches, coughs, etc.

[0009] Sinusitis is generally classified as acute (infection lasting 4 weeks or less) or chronic (12 weeks or longer). Many cases of acute sinusitis can be effectively treated with medications such as antibiotics and / or oral steroids. Chronic sinusitis sometimes requires more invasive treatment options, involving surgical access to the paranasal passages or affected sinuses.

[0010] In one example of this surgical approach, a sinus balloon can be dilated at the sinus ostium (along the outflow tract that drains sinus mucus into the nasal cavity) to open any obstructed or partially obstructed sinus ostium. The balloon is advanced into the sinus ostium, and once it is in the correct position, the user inflates it. The mechanical force exerted by the balloon causes the obstructed passage to open, allowing the mucus to drain freely from the sinus cavity.

[0011] Another form of sinus disease occurs when the inner lining of the paranasal sinuses becomes infected or thickened over a prolonged period. The infected inner lining can extend into the sinus ostia, preventing mucus from leaving the sinus cavity. Furthermore, abnormal tissues such as polyps can grow within the sinus cavity, and because they disrupt the flow of mucus within the sinus walls and cause congestion, they usually need to be removed. In some cases, the sinus cavity can be dilated to allow mucus to leave the sinus cavity and to provide a pathway for polyp removal.

[0012] Factors such as damage to surrounding tissues, patient comfort, and postoperative complications can affect the treatment of sinus diseases and conditions. For example, the amount of time a balloon needs to remain inflated in the Eustachian tube to complete the dilation procedure (e.g., 2 minutes) can cause some patients to experience discomfort due to the mechanical expansion forces exerted on the tissues—even when the patient is under local anesthesia.

[0013] The time required for intrasinus surgery can vary significantly, especially for those procedures involving the removal of tissue using rigid instruments known as conventional endoscopic sinus surgery (ESS) to treat sinus conditions. Common energy modalities may be difficult to use in sensitive structures such as the paranasal sinuses, Eustachian tubes, ear canals, and olfactory system because radiofrequency (RF), cryoablation (CA), and lasers use thermal energy to intentionally induce cell death, a process known as necrosis. Furthermore, the use of these ablation techniques can produce significant temperature variations (e.g., significantly above or below normal body temperature) at the target tissue area, which can increase the risk of unintended damage to healthy tissue in some cases. For example, if RF ablation energy is delivered to the target tissue area, the target tissue area may have a higher risk of severe crusting or scab formation compared to pulsed field electroporation (PFE) treatment. Moreover, these thermal ablation instruments (e.g., RF, CA, and lasers) can cause complications during intrasinus surgery where the thermal distribution may extend its ablation effect beyond the target tissue type and into other tissue types and adjacent structures. For example, in this energy delivery process that induces necrosis, the ablation zone extending beyond the target tissue may cause unintended damage to critical structures, such as those near the active electrode or blood vessels exposed to high temperatures.

[0014] The olfactory system is the sensory system that aids in the sense of smell. For example, it involves a complex network of olfactory receptors located in the nasal cavity. When odor molecules enter the nose, these molecules can bind to these receptors. Because olfactory nerve fibers represent specialized neurons capable of detecting many different chemical compounds, odor molecules with different chemical structures can bind to olfactory receptors in a way that elicits an electrical response in the olfactory nerve fibers. This binding can trigger a series of neural signals that can be transmitted to the olfactory bulb, a structure at the base of the brain that processes these signals and transmits them to other brain regions, including the limbic system, which is associated with emotions and memories. For example, olfactory nerve fibers can connect olfactory receptors to the olfactory bulb, allowing the receptors to send signals to the bulb via the olfactory nerve fibers. The connection between the olfactory receptors and the brain can evoke strong memories or sensations associated with certain odors.

[0015] In some cases, the tissue surrounding olfactory receptors and / or olfactory nerve fibers can become damaged over time, causing abnormal excitation or inhibition of the olfactory nerves. This condition can affect the sense of smell, leading to problems such as reduced ability to detect odors (e.g., hyposmegma), complete loss of smell (e.g., anosmegma), or distorted smell (e.g., olfactory dysmegma). Because smell is associated with taste, olfactory disorders can significantly impact quality of life. For example, olfactory disorders can affect appetite and safety, as impaired smell can prevent the detection of smoke or spoiled food. Diagnosis of olfactory disorders and conditions may involve clinical evaluation, olfactory testing, and sometimes imaging studies to identify underlying causes.

[0016] Another sensory system is the auditory system, which contributes to hearing. The auditory system includes the cochlea, a spiral-shaped, fluid-filled structure located in the inner ear. The cochlea contributes to hearing by converting mechanical sound waves into electrical signals that are transmitted to the brain. For example, the cochlea is a snail-shell-shaped container containing thousands of hair cells within a fluid. These hair cells represent sensory receptors that can convert sound vibrations into electrical signals. For example, mechanical sound waves cause waves to propagate through the fluid within the cochlea, mechanically stimulating the hair cells. Based on these mechanical movements, the hair cells can generate electrical signals. These electrical signals can be transmitted to the auditory nerve and sent to the brain. The brain processes these signals in a way that evokes hearing. The cochlea can be divided into three chambers: the scala vestibulae, the scala medialis, and the scala tympani. Each of these three chambers can play an important role in the auditory mechanism. The movement of fluid within these chambers caused by mechanical sound waves can stimulate the hair cells within the cochlea, allowing the perception of a wide range of frequencies. Damage to the cochlea can be caused by a variety of factors, leading to hearing loss. Common causes of cochlear damage include prolonged exposure to loud noise (which damages hair cells) and aging (which leads to a gradual reduction in these cells). In some cases, infections, medications (e.g., ototoxic drugs), and physical trauma can also damage the cochlea. When the hair cells within the cochlea are damaged or lost, the ability to convert sound waves into electrical signals is weakened, leading to conditions such as sensorineural hearing loss. Because cochlear hair cells do not regenerate, hearing loss conditions caused by damage to cochlear hair cells can be difficult to treat. Summary of the Invention

[0017] Some embodiments described herein may include improved systems configured to access and engage target tissue (e.g., for dilation) along the Eustachian tube, paranasal sinuses, and any other ear, nose, and pharynx site, while delivering pulsed field electroporation (PFE) to the target tissue. In specific embodiments, the system may include improved dilation devices (e.g., dilation balloons for temporary dilation of the Eustachian tube or paranasal sinus ostia) equipped with PFE electrodes configured to induce local and targeted PFE at the dilated tissue. As further described in detail below, some embodiments of the system may induce local PFE by using an electric field applied to the target tissue in a rapid burst to induce irreversible electroporation (IRE). This induces cell membrane instability, leading to a specific type of cell death called apoptosis. Therefore, these embodiments of the PFE device can treat target tissue to induce apoptosis, a cell death process similar to that of natural and controlled parts of anatomical growth or development, while avoiding the thermal ablation energy (e.g., from RF, CA, or laser ablation) that causes the aforementioned necrosis. Alternatively, the PFE system described herein can be configured to deliver PFE in a manner that selectively targets a predetermined tissue type to be treated, thereby reducing cellular inflammation and avoiding complications associated with conventional thermal ablation energy (from RF, CA, and laser), where the ablation effect extends beyond the target treatment area.

[0018] According to some embodiments described herein, improved sinus dilation systems can integrate a PFE (prosthetic pore element) to more effectively treat the Eustachian tubes or paranasal sinuses while reducing the likelihood of damage to non-target tissues (such as those that may occur with ablation devices that induce necrosis, such as RF ablation, CA, or laser ablation tools). For example, the improved systems described herein can be configured to output the PFE to selectively and non-thermally open cell pores in target tissue to induce apoptosis, which can reduce the likelihood of damage to non-target tissues such as blood vessels. In many cases, the improved systems can perform this treatment without the use of general anesthesia, thus providing additional convenience for the user and patient. For example, the improved systems can perform this treatment using (optional) topical anesthetics at the treatment site. Optionally, some variants of improved sinus dilation systems with integrated PFEs can also be used to more effectively deliver drugs (such as steroids) to target tissues. A method for tracking the treated anatomical space and correlating the treatment space with the outcome is also disclosed.

[0019] Among the options described herein, the system can be configured to deliver PFEs for one or both of two different effects to the target tissue. As mentioned above, the first type relates to irreversible electroporation (IRE), which kills cells through the apoptosis process, while the second type is reversible electroporation (RE), in which cell membrane pores dilate, allowing large molecule drugs (such as steroids) to permeate across the cell membrane without apoptosis or cell death.

[0020] In the various embodiments described below, the waveform of the PFE system can be optimized to also modulate nerves near the electroporation electrodes of the PFE device. The nerve stimulation effect is desired, thus resetting nerve activity and thereby leading to normal nerve signal communication. Nerve activity can be modulated to stimulate cell growth and repair, particularly using PFE to regenerate hair cells (e.g., cochlear hair cells). Optionally, this PFE approach can increase the benefit by modulating nerve activity to potentially reduce neural pain. In some cases, the nerve stimulation effect can be excitatory or inhibitory. For example, excitatory nerve stimulation involves increasing nerve stimulation activity, while inhibitory nerve stimulation involves decreasing nerve stimulation activity. Treatment of chronic sinusitis (CRS), chronic rhinitis (CR), and other conditions can reduce (e.g., inhibit) nerve activity, thereby reducing mucus formation to normal levels. To treat other conditions such as hearing loss or migraine-type conditions, nerve signaling can be increased (e.g., excitatory) to regenerate healthy tissue and / or nerve fibers.

[0021] Some embodiments described herein include a system comprising a nasal dilation device. The nasal dilation device may include a handle, an elongated shaft extending distally from the handle, and a treatment tip located at the distal end of the elongated shaft. Optionally, the treatment tip may have a dilation balloon and a PFE electrode, such that the treatment tip is configured to deliver PFE from the PFE electrode at nasal tissue dilated by the dilation balloon.

[0022] Further embodiments of the system described herein may include a PFE delivery device configured to enter target tissue in the ear, nose, or throat. The PFE delivery device may include a treatment tip with an expandable PFE electrode to deliver PFE to the target tissue.

[0023] Some embodiments described herein include a method comprising inserting an elongated shaft of a PFE delivery device into an ear, nose, or throat region such that an adjustable PFE electrode at a treatment tip at the distal end of the PFE delivery device is adjacent to target tissue. The method may optionally include adjusting the PFE electrode relative to the elongated shaft to press the PFE electrode against the target tissue. Furthermore, the method may include activating a PFE generator connected to a console of the PFE delivery device to output a predefined pattern of electric field from the PFE electrode, thereby inducing at least one of irreversible electroporation (IRE) and reversible electroporation (RE) at the target tissue.

[0024] Many embodiments herein include a system comprising a pulsed field electroporation (PFE) generator configured to output pulsed PFE. The system may also include a touchscreen interface coupled to the generator, configured to receive user input to control the PFE characteristics output from the generator. Optionally, the system may include a PFE delivery device comprising an elongated shaft and PFE electrodes adjustable relative to the elongated shaft to deliver PFE from the PFE generator to at least one of the following: the Eustachian tube, paranasal sinuses, middle ear, mastoid tissue, and sinus cavities.

[0025] Further embodiments described herein include a method using a pulsed field electroporation (PFE) device. This method may include advancing the treatment tip of the PFE device into the body of a subject such that a PFE electrode along the treatment tip is close to a target site. Optionally, the method may include outputting a PFE waveform from the PFE electrode of the treatment tip to induce apoptosis at the target site.

[0026] Other embodiments described herein include a pulsed field electroporation (PFE) method for treating target tissues of the ear, nose, or throat—preferably without the application of general anesthesia. This method may include pressing a PFE electrode against the target tissue while simultaneously outputting a PFE waveform from the PFE electrode.

[0027] Some embodiments described herein include a method for delivering a pulsed field electroporation (PFE) waveform to target tissue in the ear, nose, or throat—preferably without inducing necrosis at the target tissue. The method may include advancing a treatment tip of a PFE device such that a PFE electrode along the treatment tip is close to the target tissue in the ear, nose, or throat. Optionally, the method may include outputting a PFE waveform from the PFE electrode at the treatment tip to induce apoptosis at the target tissue.

[0028] Other embodiments described herein may include a system comprising a pulsed field electroporation (PFE) delivery device configured to both dilate target tissue and output PFE from a PFE electrode proximate to the target tissue. Attached Figure Description

[0029] Figure 1 A perspective view of a system for treating ear, nose, or throat tissues according to some embodiments is shown.

[0030] Figure 2 It shows Figure 1 A perspective view of the PFE console and instruments of the system.

[0031] Figure 3 yes Figure 2 A perspective view of the instrument.

[0032] Figure 4 Illustrations are shown according to some embodiments Figure 3 A side view of the distal portion of the instrument.

[0033] Figures 5A-5D The following are illustrations of a method for using according to some embodiments. Figure 1 A perspective view of the distal portion of the optional instrument of the system.

[0034] Figures 6A-6C The following are illustrations of a method for using according to some embodiments. Figure 1 A perspective view of the distal portion of the optional instrument of the system.

[0035] Figures 7A-7B The following are illustrations of a method for using according to some embodiments. Figure 1 Side view of the multi-balloon configuration of the distal portion of the optional instrument of the system.

[0036] Figures 8A-8B Various embodiments are shown within the Eustachian tube. Figure 6A and Figure 7A A side view of the instrument.

[0037] Figure 9 The following are illustrations of various embodiments of a device for use within the frontal sinus ostium. Figure 1 A side view of the distal portion of the optional instrument of the system.

[0038] Figures 10A-10B It is illustrated that various embodiments are used for Figure 1 The distal portion of the optional device in the system is in its non-expanded state within the sinus cavity. Figure 10A ) and its expansion state ( Figure 10B (Side view of ).

[0039] Figures 11A-11B It is illustrated that various embodiments are used for Figure 1 The distal portion of the optional instrument in the system is in its non-expanded position within the nasal cavity. Figure 11A ) state and its expansion state ( Figure 11B (Side view of ).

[0040] Figure 12 The following are illustrations of a method for using according to some embodiments. Figure 1 A side view of the dual-layer balloon configuration at the distal portion of the optional device of the system.

[0041] Figure 13 The following are illustrations of a method for using according to some embodiments. Figure 1 A cross-sectional perspective view of the distal portion of an optional device for the system, which includes a drug delivery option.

[0042] Figure 14 The following are illustrations of a method for using according to some embodiments. Figure 1 A side view of the system's optional instrumentation, showing a two-layer compliant balloon configuration at the distal portion that conforms to the anatomical shape.

[0043] Figures 15A-15B A perspective view of a focal device according to some embodiments is shown, the focal device may be included in... Figure 1 In the system of instruments or as Figure 1 The operation of the system's instruments.

[0044] Figures 16A-16B The following are illustrations of intracranial tissue according to some embodiments. Figures 15A-15B A side view of the focal instrument.

[0045] Figure 17 Illustrations are shown according to some embodiments Figure 1 A perspective view of the system's instruments, along with optional device connectors and image capture devices.

[0046] Figure 18 The following are illustrated according to some embodiments: Figure 17 instruments and Figures 1-2 The flowchart shows the process of using the PFE console.

[0047] Figures 19A-19B This illustrates an optional implementation of the treatment tracking algorithm. Figure 1 Medical images of the systemic instruments.

[0048] Figure 20 The following illustrates alternative methods of use according to some implementations. Figure 1 The system and the flowchart of the treatment tracking algorithm in Figure 19.

[0049] Figures 21-22 The diagram illustrates the use of some embodiments of the invention. Figure 1 An example of the PFE waveform output by the system.

[0050] Figure 23 A side view of the distal portion of an exemplary PFE delivery device for a patient's ear, according to various embodiments, is shown.

[0051] Figure 24 A side view of the distal portion of an exemplary PFE delivery device for use in a patient's sinus cavity, according to various embodiments, is shown.

[0052] Figure 25 A side view of the distal portion of an exemplary PFE delivery device for a patient's olfactory system according to various embodiments is shown.

[0053] Figure 26 A side view of the distal portion of an exemplary PFE delivery device for use in a patient's throat, according to various embodiments, is shown. Detailed Implementation

[0054] Now for reference Figures 1-3 Some embodiments of the system 10 for treating ear, nose, or throat tissue may include a pulsed field electroporation (PFE) console 100 and a PFE delivery device 200, which may be configured to enter and engage target tissue (e.g., for dilation) along the Eustachian tube, paranasal sinuses, and any other ear, nose, or throat site, while delivering pulsed field electroporation (PFE) to the target tissue. For example, user 20 may guide device 200 into the nose of patient 30 and then activate PFE console 100 so that PFE can be used to treat swollen or diseased tissue at the sinus ostia, Eustachian tube, intracranial tissue, and adjacent intrasinus tissue. Console 100 includes a generator 130 configured to output a PFE signal and a user interface 110. Device 200 is removably attached to console 100 such that console is configured to be reused over time with multiple devices 200 and to store and transmit information about those multiple devices (details below). Additionally, the device 200 includes a treatment tip 204 positioned along its distal end or the end of an elongated axis 205, and the treatment tip 204 is configured to deliver PFE via one or more electrodes, such as mesh electrodes or needle electrodes, as detailed below. Optionally, the treatment tip 204 may be equipped with an expandable member 210, such as one or more expandable balloons, to engage the PFE electrodes against target tissue such as sinus ostia, eustachian tubes, intracranial tissue, intranasal sinus tissue, etc. As described in more detail below, the system 10 may also include a foot switch 105 (for selective activation by user 20), a disposable grounding electrode pad 107 (for temporary adhesion to patient 30), an endoscope system 40 (for medical imaging during delivery and use of the device 200), and a cloud server system 50 (for remote communication with console 100).

[0055] In use, the instrument 200 is advanced to the diseased tissue that may require treatment, and then, if expansion is needed, the expandable member 210 (e.g., an expansion balloon in this example) is advanced and inflated, thereby opening the anatomical space. Next, the PFE electrode 220 is activated ( Figure 3 ) to treat target tissue via electroporation, the electroporation being controlled by console 100 ( Figure 1 The PFE electrode 220 is controlled to achieve a predetermined electric field applied to the target tissue in a rapid mode, which induces cell membrane instability at the target tissue. Optionally, the PFE electrode 220 can be coupled to a grounded electrode pad 107 mounted to the patient's body. Figure 1 They work together. Additionally, as described in more detail below, the instrument 200 can be advanced into the target anatomical space under medical imaging, for example, using an endoscopic system 40 including a handheld endoscopic instrument 45. Figure 1 The handheld endoscopic instrument 45 is configured to be operated by the user while using the PFE delivery instrument 200. In some cases, the PFE electrode 220 of the instrument 200 can be used without dilation, particularly in areas such as the sinus cavity, intracranial tissue, and other areas where dilation may not be necessary. The PFE generator of the console 100 can be accessed by pressing the user interface button 270 of the instrument 200. Figure 3 Alternatively, a foot switch 105 can be used. Figure 1 To activate. As described below, in some embodiments, console 100 can be configured to selectively enable the PFE output from generator 130 in response to an authorized device 200 connected thereto, for example, by capturing a QR code or identifier 235 at connector 230 of device 200 (see also below). Figure 17 The console 100 can communicate with the cloud server system 50 (e.g., via a wired or wireless connection to the Internet) to verify the device identifier 235 and to transmit treatment data from the console 100 to the cloud server, the treatment data indicating that a particular device 200 (with identifier 235) was used on a particular patient 30 on that date.

[0056] Now for reference Figures 3-4Some embodiments of the PFE delivery device 200 may include a control handle 260 and an elongated shaft 205 extending distally from the distal end of the control handle 260. In this embodiment, the elongated shaft 205 is a catheter shaft sized to extend into the nasal passage such that the treatment tip 204 of the device 200 extends to engage target tissue, such as the paranasal sinuses, Eustachian tube, etc. The treatment device handle 260 may include a plurality of user interface actuators, such as a PFE activation button 270, a rotary actuator 280 for actuating the tip 204 clockwise and counterclockwise (e.g., movement in the radial plane), and an articulated actuator 290 for actuating the tip 204 in an upward and downward direction (e.g., movement in the axial plane). Preferably, at least a portion of the elongated shaft 205 may be made of a malleable material in the region near the treatment tip 204, such that this portion of the shaft 205 may be bent during use.

[0057] In the depicted embodiment, the treatment tip 204 includes a PFE output electrode 220 in the form of a metal mesh (or scaffold) structure, configured to inflate and retract around a dilation balloon 210. As previously described, the dilation balloon 210 can be selectively inflated to dilate one or more narrow anatomical channels before outputting PFE from the electrode 220 (and remain dilated during PFE output from the electrode 220). For example, the balloon 210 can be inflated by injecting inflation fluid through an inflation channel 215 via an elongated shaft 205. When the inflation fluid reaches the treatment tip 204 of the device 200, the inflation fluid flows along the circumferential wall of the inflation channel 215 through the balloon port to inflate the balloon 210 to a selected pressure. Optionally, the console 100 can manage the supply of inflation fluid through the inflation channel 215 (to inflate or retract the balloon in a controlled manner) in response to actuation of a user interface button along the handle 260 (or, alternatively, a foot switch 105). The PFE electrode 220 is positioned along the outside of the balloon 210 and inflates together with the balloon 210 during inflation. After balloon inflation has been achieved, the balloon 210 remains inflated, so the PFE electrode 220 is in its inflated state and engaged with the target tissue, at which point the user can selectively activate (e.g., using button 270) the generator 130 to output PFE from the electrode 220 into the tissue. In this embodiment, the electrode 220 is connected to the instrument connector 230 via a wire 212. Figure 2The mesh electrode 220 is used for electrical connection between the generator 130 and the electrode 220 for PFE delivery. Alternatively, the mesh electrode 220 can deliver PFE without the expansion balloon 210, in which case the mesh electrode 220 can be a self-expanding structure (e.g., a stent that can be selectively expanded and retracted via the handle 260) comprising a conductive material (e.g., nitinol), thereby causing the mesh electrode 220 to contact the tissue to be treated with PFE without expanding the balloon at the treatment tip 204.

[0058] Now for reference Figures 5A-5D Various embodiments of the PFE delivery device 200 may optionally include different electrode geometries and components. For example, such as Figure 5A (and) Figures 3-4 As shown in the diagram, the treatment tip 204 of the device 200 includes a mesh PFE electrode 220a. In some examples, Figure 5A The electrode 220a depicted in the image is Figure 3 and Figure 4 An example of electrode 220 depicted in the image. Figure 5B As shown, some embodiments of device 200 may include a helical PFE electrode 220b surrounding balloon 210. Alternatively, some embodiments of device 200 may include a surface PFE electrode 220c mounted along the exterior of balloon 210. Figure 5C ) or 220d ( Figure 5D It may have corresponding electrical leads extending to the proximal end for the purpose of achieving bipolar output (e.g., eliminating...). Figure 1 (The grounding pad 107 depicted herein is required). In these embodiments, the balloon 210 shown here can be used to press any of the electrodes 220a-220d against the target tissue for PFE delivery. In some cases, the balloon 210 can be used to expand the tissue (and then fully or partially close it) before PFE delivery. Figures 5A-5B The electrodes 220a and 220b shown can be fixedly mounted to the outer surface of the balloon 210, for example, where the balloon 210 will be inflated to a predetermined pressure and size. Figures 5C-5D The electrodes 220c and 220d shown may each include electronic circuitry directly attached to the outer surface of the balloon 210, allowing the electrodes 220c and 220d to be adjusted to engage with the tissue (when the balloon 210 is inflated). This is possible when the PFE can be delivered over the entire circumferential region around the balloon 210 where the electrodes 220a or 220b are in contact with the tissue. Figures 5A-5B The option of electrodes 220a or 220b can be particularly useful. Figures 5C-5DThe option of electrodes 220a or 220b can be particularly useful, for example, in which the user can selectively activate each isolated electrode 220c or 220d (directional PFE delivery) or deliver PFE in a bipolar manner (where one electrode 220c or 220d is positive and the other similar electrode 220c or 220d is negative, and they alternate as PFE is delivered).

[0059] Now for reference Figures 6A-6C Various embodiments of the PFE delivery device 200 may optionally include multiple balloons along the treatment tip 204. And such multi-balloon embodiments can provide different electrode geometries and components. For example, as... Figure 6A As shown, the treatment tip 204 of the device 200 may include a series of inflatable balloons 211a-211d (collectively referred to as “balloons 211”) positioned adjacent to each other along the treatment tip 204, wherein all balloons 211 are surrounded by the aforementioned mesh PFE electrode 221a. In some cases, the mesh PFE electrode 221a is similar to Figures 3-4 Mesh PFE electrode 220 and Figure 5A The mesh PFE electrode 220a. The mesh PFE electrode can be configured with various patterns. For example, such as... Figure 6A The depicted mesh PFE electrode 221a includes multiple pillars defining multiple rhomboid openings. As depicted in Figure 5, as... Figure 5A and 6A As shown, the mesh PFE electrode 220a includes multiple pillars defining multiple rhomboid openings and multiple hexagonal openings. The mesh PFE electrode of this disclosure is not limited to... Figure 5A and 6A The patterns depicted in Figures 5A and 6A. The mesh PFE electrodes define patterns not depicted in Figures 5A and 6A.

[0060] like Figure 6B As shown, the treatment tip 204 of the device 200 may include a series of inflatable dilatation balloons 211 positioned adjacent to each other along the treatment tip 204, wherein all balloons 211 are surrounded by the aforementioned helical PFE electrode 220b (similar to...). Figure 5B ).like Figure 6C As shown, the treatment tip 204 of the device 200 may include a series of inflatable balloons 211 positioned adjacent to each other along the treatment tip 204, wherein each individual balloon 211 is surrounded by a corresponding mesh PFE electrode in a mesh PFE electrode 222a-222e (collectively referred to as “electrode 222”). For example, Figure 6CThe treatment tip 204 includes four balloons 211 and four corresponding mesh PFE electrodes 222, wherein mesh PFE electrodes 222a surround balloon 211a, mesh PFE electrodes 222b surround balloon 211b, mesh PFE electrodes 222c surround balloon 211c, and mesh PFE electrodes 222d surround balloon 211d.

[0061] exist Figures 6A-6C In these depicted embodiments, balloons 211 are spaced apart from each other along axis 205 by a balloon separation distance 225 ( Figure 6C As previously described, for embodiments of the treatment tip 204 including multiple PFE electrodes, for example... Figures 5C-5D and Figure 6C In a multi-electrode configuration, device 200 can be configured to provide bipolar output of PFE in a manner that further optimizes the directionality or local surface concentration of PFE delivery, since the PFE output is delivered between adjacent electrodes 220c, 220d, or 222 at the treatment tip 204 of device 200. In other cases, the multi-electrode configuration can be activated in a unipolar manner (e.g., with grounded electrode pad 107). Figure 1 (Used in combination) to provide a deeper tissue treatment area.

[0062] Now for reference Figures 7A-7B Some embodiments of the PFE delivery device 200 may optionally include multiple balloons along the treatment tip 204. And such a multi-balloon embodiment may each include a surface-mounted PFE electrode. For example, as... Figure 7A As shown, the treatment tip 204 of the device 200 may include a series of inflatable dilatation balloons 211, similar to those previously combined Figures 6A-6C Those described (e.g., four sacs 211 of the same size and inflated shape, spaced apart by a spacing distance 225 to expose the intermediate shaft portion 226). As... Figure 7A As depicted, each balloon 211 may be equipped with multiple surface-mounted PFE electrodes from a set of surface-mounted PFE electrodes 223a-223h (collectively referred to as "electrodes 223"). For example, balloon 211a is equipped with surface-mounted electrodes 223a and 223b. Balloon 211b is equipped with surface-mounted electrodes 223c and 223d, and so on. Figure 7A In one embodiment, the surface-mounted electrode 223 includes a metal ring structure that can be fixedly mounted along the outer circumferential surface of each balloon 211.

[0063] like Figure 7BAs depicted, the treatment tip 204 of the device 200 may include a series of inflatable balloons 213a-213e (collectively referred to as “Balloons 213”) of different sizes or shapes. For example, Balloons 213 may include a first group of balloons with the largest size (e.g., Balloons 213a and 213e), a second group of balloons with medium sizes (e.g., Balloons 213b and 213d), and a balloon 213c with the smallest size. Balloons 213 may be arranged in series and spaced apart by a separation distance to expose the intermediate shaft portion 226. In some cases, each of the balloons 213 is equipped with multiple surface-mounted PFE electrodes from a set of surface-mounted PFE electrodes 227a-227j (collectively referred to as “Electrodes 227”). For example, Balloon 213a is equipped with surface-mounted electrodes 227a and 227b, Balloon 213b is equipped with surface-mounted electrodes 227c and 227d, and so on. Figure 7A and 7B As depicted, even when the balloon is inflated, the spacing 225 between the balloons 211 and 213 can provide increased flexibility and maneuverability of the treatment tip 204, thereby providing a treatment tip that can conform to the shape of an anatomical structure (e.g., the tortuosity of the sinus ostium).

[0064] For example, such as Figures 8A-8B As depicted in the illustrated embodiments, the Eustachian tube or other anatomical cavities in the ear, nose, and pharynx region may include tortuous paths into which the treatment tip 204 can be advantageously inserted to deliver dilation therapy, PFE therapy, or a combination thereof. In this example, the Eustachian tube has an S-shaped path, and the treatment tip 204 of the instrument can be configured for dilation while reducing balloon slippage during inflation due to the anatomical passage not being perfectly longitudinally straight or symmetrical. Figure 8A In the depicted example, the treatment tip 204 may have a configuration including multiple balloons 211 and mesh electrodes 221a, similar to Figure 6A The configuration is shown. In some cases, a series of balloons 211 can significantly reduce the likelihood of the treatment tip 204 slipping out of position during balloon inflation compared to embodiments using a single balloon. For example, the intermediate shaft portion can have increased flexibility due to the small gap between each pair of consecutive balloons 211, which allows the tip 204 to conform to the curvature of the anatomical channel.

[0065] Similarly, in Figure 8B In the depicted example, the treatment tip 204 may have a configuration with multiple balloons 211 and surface-mounted electrodes 223 for each balloon 211, similar to Figure 7AThe embodiments described above. Similarly, compared to embodiments using a single balloon, a series of smaller balloons 211 can significantly reduce the likelihood of the treatment tip 204 slipping out of position during balloon inflation. For example, the small gaps between each balloon 211 increase the flexibility of the intermediate axis portion between the balloons 211, allowing the tip 204 to conform to the curvature of the anatomical channel.

[0066] In some embodiments, the treatment tip 204 may include a configuration of balloons of different sizes, similar to... Figure 7B Examples of embodiments. For instance, the first balloon (e.g., balloon 213a) and the last balloon (e.g., balloon 213e) in a series of balloons 213 can be larger than the other balloons in the series of balloons 213. This allows balloons 213a and 213e to act as anchors upon inflation, thereby stabilizing intermediate balloons 213b, 213c, and 213d, while all balloons 213b, 213c, and 213d inflate within a tortuous path to expand the target tissue and deliver PFE treatment. In these embodiments described above, the spacing of the successive balloons at a distance of 225 provides increased flexibility to the treatment tip 204, allowing it to easily adapt to complex shapes, such as an S-shaped Eustachian tube, even when the balloons are fully inflated.

[0067] Therefore, as Figures 1-8B As illustrated in the examples, the PFE delivery device 200 of System 10 can optionally be implemented by integrating a PFE electrode with an expansion balloon to increase tissue treatment options using a single device (during a single surgical intervention), while also increasing the likelihood of improved surgical outcomes. For example, the various embodiments described herein can simultaneously achieve mechanical dilation of the obstructed channel while also delivering PFE from a PFE electrode engaged with the target tissue to induce apoptosis in abnormal / disease-affected cells, which can advantageously induce healthy regeneration and proliferation of new cells. Optionally, some types of PFE electrodes (as described above) may include a self-expanding scaffold structure that engages against the target tissue to deliver PFE without balloon dilation of the tissue; this can be used in spaces such as the Eustachian tube, paranasal sinuses, and intrasinusoids. This alternative approach may be desirable for procedures where significant dilation and / or reshaping of the tissue channel is not required before PFE delivery.

[0068] Based on the teachings of this article and in conjunction with Figures 1-8B The described examples demonstrate how various balloon configurations and PFE electrode structures can be implemented in the PFE delivery device 200. Furthermore, based on the teachings of this paper, Figures 4-8B Any features of the embodiments depicted herein may be related to Figures 4-8BAdditional features of other embodiments depicted herein are used in combination. Furthermore, based on the teachings herein, the PFE electrode can include a variety of shapes and structural configurations, ranging from partially covering the balloon to fully covering it, and even those implemented along the PFE delivery device 200 without any dilation balloon.

[0069] Furthermore, based on the teachings and combination of this article Figures 1-8B For example, it should be console 100 ( Figure 1 The PFE generator 130 can be configured to output various PFE waveforms from the aforementioned PFE electrode structure. In a particular embodiment described herein, the PFE output by the generator 130 and delivered from the device 200 provides an electric field that is applied to the target tissue in a series of rapid bursts to induce electroporation at the target tissue, thereby inducing cell membrane instability to induce apoptosis without thermal ablation effects (e.g., tissue necrosis). Optionally, the PFE output by generator 130 and delivered from device 200 can provide highly effective treatment at target tissues within the ear, nose, or throat, while offering greater convenience to clinicians and patients—for example, when the patient is awake (e.g., avoiding general anesthesia) and only local topical anesthetics are used (e.g., temporary effectiveness and rapid recovery). In one example, PFE generator 130 can be configured to output PFE (delivered from treatment tip 204 of device 200) in the form of an electric field with a PFE waveform having a voltage amplitude greater than 800 volts and a pulse width no greater than 5 microseconds (e.g., preferably a pulse width of 50 nanoseconds to 3 microseconds), which can result in sufficient PFE to induce apoptosis in the treated tissue while avoiding thermal ablation effects (e.g., avoiding necrosis). Additional options for the characteristics of the PFE waveform that can be used in the specific embodiments described herein are described in more detail below.

[0070] Now for reference Figure 9 Some embodiments of system 10 include the use of the PFE delivery device 200 in conjunction with an illumination element, medical imaging, or both. For example, certain types of anatomical structures, such as the frontal sinus 33 of patient 30, may be difficult to access, and the device 200 may include a transdermal illumination LED 250 positioned along the treatment tip 204 (e.g., at the most distal end of the treatment tip 204) so ​​that the user can confirm access to the target anatomical cavity by illuminating the tip 204 with sufficient light for transdermal observation (observable by a physician's eye). Alternatively, the LED 250 may be replaced by or combined with an electromagnetic marker or sensor, which may also be used to confirm anatomical location with high precision relative to CT or MRI images. As previously combined... Figures 1-8BThe treatment tip 204 may include at least one dilating balloon (e.g., any one or a combination of balloons 210, 211, 213), at least one PFE electrode (e.g., any one or a combination of electrodes 220, 221, 222, 223, 227), or a combination of both. This can treat the ostia of the paranasal sinuses by opening the obstructed passage via dilation, by constricting inflammation of the sinus ostium tissue using the PFE, or by performing dilation and delivery of the PFE.

[0071] Now for reference Figures 9-11B Some embodiments of system 10 include a PFE delivery device 200 with adjustable PFE electrodes that are adjustable to conform to the shape of an anatomical cavity, optionally without the use of an inflatable balloon. For example, the PFE delivery device 200 can be used in anatomical spaces such as sinus cavities 33 with accumulation of pathological cells, resulting in mucosal thickening, sinus infection, or other related conditions. In this embodiment, the treatment tip 204 of the device 200 includes a user-controlled, inflatable mesh PFE electrode 231 that can be actuated (e.g., via a handle 260) Figure 3 (Extending to one or more control lines of the dial or other actuator) to continuously expand and conform to the cavity volume 33, such as Figures 10A-10B As shown. An expandable mesh PFE electrode 231 is used to deliver PFE therapy (e.g., via button 270). Figure 3 After activation, the user can collapse the mesh PFE electrode 231 (e.g., using one or more control lines) to withdraw the treatment tip 204 from the cavity 33. Alternatively, a compliant balloon located within the mesh structure of electrode 231 can be used to inflate the PFE electrode 231, the compliant balloon flexibly expanding and conforming to the shape of the cavity being treated upon inflation. Additionally, in Figures 10A-10B In other embodiments besides the sinus cavity example depicted, the PFE delivery device can be delivered to other anatomical structures (such as... Figures 11A-11B The nasal passage 37 shown is then inflated with a compliant balloon to expand the PFE electrode 231.

[0072] PFE is used inside the sinus cavity. Figure 9 and Figures 10A-10B It can treat chronic infections and biofilms by killing diseased tissue and / or antigens that cause biofilms, chronic infections, and / or mucosal thickening via apoptosis, while simultaneously stimulating the regeneration of PFE-delivering tissue along with healthy tissue. This is achieved by the apoptotic process triggering T cells and other anti-infection cells to reach the PFE delivery area, where dead apoptotic cells are removed by T cells while the tissue regenerates with healthy, non-infectious tissue.

[0073] Through the protective matrix of extracellular polymeric material (EPS), biofilm bacteria are shielded from environmental stresses such as antimicrobial agents, making biofilms significantly more difficult to eradicate. Biofilms can form in a variety of tissues, including the paranasal sinuses and sinus cavities. Bacteria within biofilms often exhibit unique behaviors and interactions, including enhanced nutrient and genetic exchange, which contribute to their resilience and adaptability. Biofilms play important roles in both beneficial processes (e.g., biorepair) and harmful environments (e.g., chronic infection). In cases where biofilm bacteria induce chronic infection leading to the breach of the biofilm and viable bacteria within the EPS layer, PFE can be applied. For example, within the sinuses, PFE can be activated, such as... Figure 9 and Figures 10A-10B As shown, PFE can kill excess bacteria in biofilms because it can penetrate the EPS layer that shields bacteria. Furthermore, PFE can be used to disrupt the biofilm matrix, thereby significantly reducing bacterial resistance to drugs and antibiotics, which can be used in conjunction with PFE or administered later to eradicate bacteria.

[0074] Now for reference Figures 12-13 Some embodiments of system 10 include a PFE delivery device 200, wherein a treatment tip 204 is configured to simultaneously deliver a drug or other therapeutic agent to a target tissue and deliver PFE therapy. For example, console 100 ( Figure 1 The device can be configured to output PFE from the treatment tip 204 to open the pores of cells for reversible electroporation (where cells absorb drugs or other therapeutic agents much faster than when not exposed to PFE), while the treatment tip 204 also outputs a fluid delivery of drugs or other therapeutic agents. Figure 12 In the depicted embodiment, the treatment tip 204 includes two balloon structures—an inner balloon 218a and an outer balloon 218b, the inner balloon 218a being connected to… Figures 3-5DThe outer balloon 218b operates similarly to expand in size and press the mesh PFE electrode against the target tissue. The outer balloon 218b includes an external aperture 217 for outward delivery of a fluid drug or agent to the target tissue. The aperture 217 of the outer balloon 218b can expel fluid, such that when the drug or agent is delivered between the inner balloon 218a and the outer balloon 218b, the aperture 217 through the outer circumferential surface of the outer balloon 218b expels the fluid drug or agent outward toward the target tissue, which is also in contact with the mesh PFE electrode 220. The electrode 220 can deliver the PFE before, during, or after the delivery of the drug or agent to the tissue through the aperture 217. In this embodiment, the elongated shaft 205 is equipped with a plurality of lumens, including an inflatable lumen 215 (for delivering inflatable fluid into the inner balloon 218a), a first fluid delivery lumen 224 (fluidly communicating with the outer balloon 218b via one or more ports 234, such that a first drug or agent can be delivered from an aperture 217 of the outer balloon 218b), and a second fluid delivery lumen 225 (fluidly communicating with the outer balloon 218b via one or more ports (e.g., like port 234), such that a second drug or agent can be delivered from an aperture 217 of the outer balloon 218b). Therefore, the first fluid delivery lumen 224 and the second fluid delivery lumen 225 can be used to deliver different types of drugs through the outer balloon 218b, and the inflatable lumen 215 is isolated and communicated with the inner balloon 218a to inflate the inner balloon 218a.

[0075] refer to Figure 14 Another embodiment of system 10 can simultaneously deliver drugs or other therapeutic agents to the target tissue and deliver PFE treatment. Here again (similar to...) Figures 12-13 As illustrated in the previous example), console 100 can be configured to output PFE from treatment tip 204 to open the pores of cells for reversible electroporation (where cells absorb drugs or other therapeutic agents much faster than when not exposed to PFE), while treatment tip 204 also outputs fluid delivery of drugs or other therapeutic agents. Figure 14 In the depicted embodiments, the balloon may be a compliant balloon that expands flexibly to conform to the shape of the anatomical cavity together with the conformal mesh PFE electrode 231 (see also, for example, the compliant balloon). Figures 10A-10B and Figures 11A-11B For example, the treatment tip 204 may include an internal compliance balloon 219a that operates to expand in size and press the mesh PFE electrode 231 against the target tissue. The treatment tip 204 may also include an external compliance balloon 219b that includes an external aperture (e.g., similar to...). Figure 13The aperture 217 shown is used to deliver a fluid drug or agent to the target tissue. An expandable mesh PFE electrode 231 can be located outside the external compliant balloon 219b. When the inner balloon 219a inflates, the PFE electrode 231 can conform to the treated cavity 33, achieving at least partial contact with the tissue surface within the cavity 33. Furthermore, during or after the expansion of the PFE electrode 231, a fluid drug or agent can be delivered between the inner balloon 219a and the outer balloon 219b (e.g., similar to...). Figures 12-13 The operation of the treatment tip 204, which includes port 234 and hole 217, as depicted in the figure, allows fluid drugs or agents to be delivered through holes in the outer circumferential surface of the outer balloon 219b toward the target tissue stimulated by the mesh PFE electrode 231.

[0076] Now for reference Figures 15A-16B Some embodiments of system 10 include a PFE delivery device 200, wherein the treatment tip 204 includes a movable needle-like PFE electrode 232 configured to deliver PFE over a small, predetermined area on the surface of a target tissue region. Figures 15A-15B In the depicted embodiment, the treatment tip 204 includes a plurality of needle-like electrodes 232 slidable relative to an elongated shaft 205, in this embodiment, the elongated shaft 205 including a distal opening 206. Each needle-like electrode 232 may include a needle-like shaft body extending distally to a curved region and then distally to an electrode needle-like tip. Figure 15A and Figure 16A As depicted, the needle-shaped PFE electrode 232 can be advanced to a first extension distance distal to the distal opening 206, such that the PFE output from the needle-shaped PFE electrode 232 is primarily along the tissue (e.g., as shown in the image). Figure 16A The surface of the depicted pituitary gland or other intracranial tissue is delivered to a small targeted area. For example... Figure 15B and Figure 16B As shown, the needle-shaped PFE electrode 232 can be advanced a second, greater extension distance distal to the distal opening 206, such that the PFE output from the needle-shaped PFE electrode 232 is delivered to the submucosal depth of the targeted small region (again, for example, in...). Figure 16B (At the depth of the pituitary gland or other intracranial tissues shown). In this type of intracranial surgery, especially when the diseased cells are located in the submucosa, the needle-shaped PFE electrode 232 at the treatment tip 204 (as shown) Figure 16B (As shown) can be advantageously advanced to the submucosal depth, thereby delivering PFE close to the diseased tissue.

[0077] Now for reference Figure 17 In some embodiments, device 200 may be equipped with an identifier (e.g., QR code 235), which may be provided by console 100. Figure 1The console can read and thus affect the operation of system 10. For example, when the console captures the QR code 235 of a specific device 200 that releasably mates with the PFE generator 130 of console 100, the console can identify the type of device 200 and, in response, enable the generation of PFE output (because device 200 is an authorized device), modify the characteristics of the PFE output (e.g., induce IRE or RE, treat surface tissue or submucosal tissue, etc.), and communicate with cloud server system 50 (e.g., via a wired or wireless connection to the Internet) to transmit treatment data from console 100 to cloud server 50, which indicates the use of a specific device 200 (with identifier 235), or a combination thereof, on a specific patient 30 on that date. Additionally, in response to console 100 capturing the device's QR code or other identifier 235, console 100 can communicate with cloud server system 50 (e.g., via a wired or wireless connection to the Internet) to verify that the specific device 200 is authorized for use. Figure 17 As shown, in this embodiment, the identifier is a QR code 235 fixed to the instrument connector 230 of the selected instrument 200 (e.g., at the proximal end of cable 265, while the handle 260 is at the distal end of the same cable 265), which is shaped to be compatible with the console 100. Figure 1 The generator 130 cooperates with the device 200. In this embodiment, each QR code 235 is unique for its specifically associated device 200 and can be authorized for use only once (e.g., via verification at cloud server 50), thereby ensuring the hygienic disposal of each device 200 after its first use and further confirming the PFE signal output to the authorized device for consistent safety. In this example, the QR code 235 attached to the device connector 230 is generated by the console 100 ( Figure 1 The user interface 110 is captured by camera 114. For example, user interface 110 may include a tablet device with a touchscreen and a camera mounted adjacent to the touchscreen display. In use, the user interface may be prompted to activate the camera to use the console with the new instrument 200, and an on-screen prompt will remind the user to scan a QR code using camera 114. The tablet device may be movable relative to generator 130 of console 100, such that when connector 230 is inserted into generator 130 (… Figure 1 Afterwards, camera 114 can be pointed at QR code 235 on connector 230, or QR code 235 on connector 230 can be positioned in front of camera 114 on user interface 110 before connector 230 is inserted into generator 130. In response to QR code 235 being captured and then authorized for use with PFE generator 130 (via connection to cloud server 50), QR code 235 can also be assigned to patient 30. Figure 1This can be recorded, or otherwise, in the patient's electronic health record (EHR) file associated with the medical procedure, allowing the patient to monitor the effectiveness of the procedure over time. The QR code 235 can also be used to automatically report complaints or defects (e.g., using the user interface 110 of the console 100 communicating with the cloud server 50 to report such a problem with a specific device 200), or to prevent the product from being used for a certain output type (e.g., when device 200 includes a fluid drug delivery lumen). Figures 12-13 (To prevent PFE output from inducing IRE when used in conjunction with different PFE outputs that induce RE during drug delivery).

[0078] Now for reference Figure 18 Some embodiments of the process 1800 for delivering the device 200 using a PFE (e.g., a QR code 235) may include an operation 1810 for generating a unique code for each device. For example, a QR code may be generated for the device at a manufacturing facility where the device 200 is also manufactured. When generating the QR code, a computer system at the manufacturing facility adds the QR code to a file stored on an external cloud server 50. Figure 1 The database contains the information. In Operation 1820, when the user begins surgery, the console's camera scans the QR code attached to the instrument (e.g., see reference). Figure 1 and Figure 17 In response to scanning the QR code in the console, the console queries cloud server 50 ( Figure 1The cloud server 50 compares the scanned QR code with the database to confirm whether the device is authorized for use (e.g., a new device). If the QR code indicates that the device is authorized, the console receives this authorization indication and starts the PFE generator to prepare for the output of PFE treatment with the correctly connected device. Alternatively, if the QR code indicates that the device has been used previously or is otherwise unauthorized, the console receives this unauthorized device indication and disables the PFE generator (or maintains its disabled state). In operation 1830, after confirming authorization for the use of the device 200 with the QR code, data generated during the procedure, such as medical images of the anatomical location for PFE delivery during use, is stored locally on the console (and optionally uploaded to the cloud server 50) and linked to the QR code initially scanned in operation 1820. Optionally, when scanning the QR code, the console automatically stores the device identifier and the location where the device is being used (e.g., a designated location with the console). Therefore, in operation 1840, if an error occurs during the procedure, the console automatically sends error-related information to the cloud server 50. Furthermore, in operation 1850, the QR code scanned in operation 1820 can also be associated with a specific patient using the instrument. For example, during surgery, data such as endoscopic images are stored in a folder with the same name as the QR code. After the procedure, the QR code can be provided to the patient, stored in the patient's electronic health record (EHR), or both. When the doctor or patient subsequently scans the QR code using a smartphone, tablet, or console, a hyperlink is displayed to provide access to the data generated during the procedure.

[0079] Now for reference Figures 19A-19B As previously described in some embodiments, the instrument 200 can be coupled with the endoscope 45 ( Figure 1 This is used in conjunction with other methods to provide medical imaging of the treatment tip 204 within the patient's body during PFE delivery to the target tissue. In many cases, the PFE output from the treatment tip 204 may not result in visible markings or discoloration on the treated tissue, but the system described in this embodiment can optionally provide the ability to visually record and track the anatomical location of previously treated tissues for each particular patient. Figures 19A-19B In the depicted embodiment, the treatment tip 204 of the instrument 200 may include a dome-shaped PFE electrode 220h (although any other electrodes 220 and 220a-g could also be implemented here) and a marking band 228 for positioning adjacent to the electrode 220h. Endoscope 45 ( Figure 1 The device is advanced to a position adjacent to the treatment tip 204 to provide video data on the use of the treatment tip 204 in an anatomical cavity (e.g., nasal cavity 33 in this example). Console 100 ( Figure 1The system is configured to receive video data from the endoscope system 40 and generate (and then store) one or more new medical images that mark the treatment site 229. Figure 19B This image is superimposed on the original medical image recorded by the endoscope at a specific location where the PFE is output from electrode 220h. In this embodiment, the position of band 228 (or optionally, electrode 220h itself) is continuously tracked in the endoscopic video data using a machine learning algorithm. This algorithm, upon activation of the PFE output from electrode 220h, then identifies the location within the endoscopic image where the PFE is delivered to the tissue and stores such a new image in the memory of console 100. Figure 19B As shown, marker 229 depicts the historical treatment area where PFE was delivered within the nasal cavity 33. The marker can be color-coded; for example, different colors can be used to indicate different amounts of PFE delivered.

[0080] Now for reference Figure 20 Some implementations of the process 2000 for tracking the position of the treatment tip and generating markers for the treatment position (e.g., such as...) Figures 19A-19B (As shown) may include operation 2010 of recording an endoscopic view of a PFE delivery instrument having a band or other unique feature that is visible and detectable within the endoscopic image. For example, treatment tip 204 may include a control console (which is accessible from endoscopy system 40) Figure 1 The system receives endoscopic video data in real time and executes AI image recognition software to detect physical features. In operation 2020, in response to the user activating the PFE electrode to output PFE treatment at an adjacent tissue site, an image of the endoscopic view is captured and stored on the console. In operation 2030, the captured endoscopic image is modified to include one or more markers (reference) at the AI-detection locations of the electrode(s) when the PFE is activated. Figure 19A Electrode 220h and Figure 19B (Mark 229 in the image). Markers can be added to endoscopic images of the anatomical cavity when the treatment tip resides within it, or to endoscopic images of the anatomical cavity recorded when the treatment tip is not in the field of view (e.g., before or after insertion of the treatment tip). In operation 2040, modified medical images (including marks) and other surgical data can be transferred from the console to cloud server 50 (…). Figure 1 ), and optionally, can be presented to users in the clinical setting at the user interface 110 of the console 100.

[0081] Now for reference Figures 21-22 Console 100 ( Figure 1Some embodiments of the PFE generator 130 can be configured to perform PFE in the form of a PFE waveform to induce apoptosis in the treated tissue. In this embodiment, as previously described, the PFE output from the generator 130 and delivered from the device 200 provides an electric field that is applied to the target tissue in a rapid burst manner to induce electroporation, thereby inducing cell membrane instability to induce apoptosis, and preferably, while avoiding thermal ablation energy (e.g., from RF, CA, or laser ablation) that induces the aforementioned tissue necrosis. For example, as Figure 21 As shown, the generator can be configured to output a PFE waveform with an amplitude 2100 greater than 800V (preferably between 800V and 5kV in this example) and a pulse width 2106 less than 5 microseconds (preferably about 50 nanoseconds to 3 microseconds in this example), such that a sufficient electric field exists to result in PFE treatment without thermal ablation effect at the tissue site. Figure 21 As shown, each burst 2104, 2107 may include a set of predefined pulses, and in this example, each set of pulses may include 1 to 1,000 pulses (pulses in... Figure 21 (Numbered in the diagram). The pulse pattern 2101 within each burst 2104, 2107 can be separated by a pulse delay 2103 (between 1 microsecond and 1000 microseconds in this example), so that the delivery of PFE can stimulate nerves near the PFE electrode in addition to inducing the aforementioned apoptosis. Furthermore, a series of multiple bursts can be delivered (e.g., see reference). Figure 21 The intensity of neural stimulation can be increased by bursts 2104 and 2107, and successive bursts can be separated by a burst delay 2105 of at least 50 milliseconds. In this case, the burst delay 2105 between the first burst 2104 and the subsequent burst 2107 can be long enough to allow neural stimulation to be completed during the first burst 2104 before the output of the subsequent burst 2107. Within each burst 2104, 2107, the frequency of the pulse can be set to a value of approximately 400 kHz to approximately 10 MHz (this can be achieved by generator 130). Figure 1 This is achieved by adjusting the value of the pulse delay 2103 between each pulse. Furthermore, for each series of bursts (refer to the first burst 2104 and subsequent bursts 2107), the burst frequency can be set to a value of approximately 1 Hz to approximately 400 kHz (this can be achieved by the generator 130). Figure 1 This is achieved by adjusting the value of burst delay 2105. (For example...) Figures 21-22 As shown, pulses can have positive, negative, or both polarity (see [reference]). Figure 22 (Positive polarity 2200 and negative polarity 2201). For example... Figure 22As shown, the amplitude combination of positive 2200 and negative 2201 polarities can be delayed by 2202, or it can be continuous without the delay of transitioning from one amplitude polarity to the next. Therefore, as Figure 22 As shown in the example, the PFE output from the PFE generator can include a PFE waveform with a repetitive pattern to provide overall bias energy of positive polarity (which will not cause muscle contraction). The repetitive pattern includes a positive pulse, a negative pulse, and another positive pulse (see reference). Figure 22 (Left and middle). Alternatively or additionally, the PFE output from the PFE generator may include a PFE waveform with a repetitive pattern to provide overall bias energy of negative polarity (without causing muscle contraction), the repetitive pattern including a negative pulse, a positive pulse, and another negative pulse (see reference). Figure 22 (on the right side).

[0082] The system of claim 21, wherein the PFE output from the PFE generator comprises a PFE waveform having a repetitive pattern to provide positive polarity bias energy in the absence of muscle contraction, the repetitive pattern comprising a single positive pulse, a single negative pulse, and a single positive pulse.

[0083] Now for reference Figure 23 PFE delivery device (e.g., similar to Figures 10A-10B and Figures 11A-11B One or more embodiments of the PFE delivery device 200 described herein may include a self-expanding mesh electrode 2300 comprising a conductive material such as nitinol and other materials. This self-expanding mesh electrode 2300 may be used for therapeutic purposes. Figure 23 The diseased anatomical region of the ear 2301 within the treatment boundary 2307 depicted in the diagram. In some cases, the self-expanding mesh electrode 2300 may be secured to the distal end of the delivery shaft 2302. The delivery shaft 2302 may include methods for electrically connecting the self-expanding mesh electrode 2300 to a PFE generator (e.g., Figures 1-2 The PFE generator 130 has internal conductor leads. In some cases, the dimensions of the delivery shaft 2302 and the self-expanding mesh electrode 2300 allow the self-expanding mesh electrode 2300 to be advanced through the patient's ear canal 2310, through the tympanic membrane 2303, and into the middle ear 2312. In the middle ear 2312, the self-expanding mesh electrode 2300 can deliver PFE to the target treatment site.

[0084] In some examples, the delivery shaft 2302 may represent an elongated member resistant to bending moments, making the delivery shaft 2302 rigid enough to advance through the patient's anatomical passage. In some cases, the delivery shaft 2302 includes an outer sheath and an inner member sized to pass through the lumen of the outer sheath. In some embodiments, the inner member can be moved proximally or distally relative to the outer sheath through the lumen defined by the outer sheath. For example, a self-expanding mesh electrode 2300 may be attached to the distal end of the inner member such that when the self-expanding mesh electrode 2300 is in a retracted state, it can fit within the lumen defined by the outer sheath. The inner wall of the outer sheath, for example, can hold the self-expanding mesh electrode 2300 in the retracted state and prevent it from transitioning to an expanded state. This can facilitate delivery through the tympanic membrane (which may optionally be accessed via a small incision of 1 mm to 4 mm (preferably less than 3 mm) so that the tympanic membrane can heal itself after the system is withdrawn from the ear canal). When the internal components move distally relative to the outer sheath, the self-expanding mesh electrode 2300 can protrude from the distal opening of the outer sheath and change from a retracted state to an expanded state. In embodiments where the self-expanding mesh electrode 2300 comprises nitinol, when the self-expanding mesh electrode 2300 emerges from the outer sheath, it can automatically expand because the outer sheath no longer holds it in the retracted position.

[0085] In some cases, the self-expanding mesh electrode 2300 can be in a retracted state as it is advanced through the ear canal 2310, through the tympanic membrane 2303, and into the middle ear 2312, and can transition from a retracted state to an expanded state within the middle ear 2312 near the target treatment site. For example, when the delivery shaft 2302 includes an outer sheath and an internal member attached to the self-expanding mesh electrode 2300, the internal member can be moved distally relative to the outer sheath such that when the self-expanding mesh electrode 2300 is within the middle ear 2312, the self-expanding mesh electrode 2300 is away from a distal opening in the outer sheath. This allows the self-expanding mesh electrode 2300 to automatically transition from a retracted state to an expanded state.

[0086] In some embodiments, the diameter of the self-expanding mesh electrode 2300 in its retracted state may be less than or equal to the diameter of the delivery shaft 2302. For example, in embodiments where the delivery shaft 2302 includes an outer sheath and an internal member, the retracted self-expanding mesh electrode 2300 may be fitted within a cavity defined by the outer sheath, such that the diameter of the outer sheath is greater than the diameter of the retracted self-expanding mesh electrode 2300. This allows the self-expanding mesh electrode 2300 and the delivery shaft 2302 to reach the middle ear 2312 through the ear canal 2310 and through the tympanic membrane 2303 (e.g., through a small surgical opening in the tympanic membrane 2303).

[0087] As described above, the self-expanding mesh electrode 2300 can be attached to the distal end of the delivery shaft 2302, which can be advanced through the ear canal 2310 and through the tympanic membrane 2303 to reach the middle ear 2312. Within the middle ear 2312, the self-expanding mesh electrode 2300 can stimulate portions of the patient's anatomical structures, such as the cochlea 2304, mastoid air cells 2305, cochlear nerve fibers 2306, vestibule 2308, tympanic membrane 2303, and other anatomical structures. For example, the self-expanding mesh electrode 2300 can deliver PFE near the cochlea 2304 to stimulate the cochlear nerve fibers 2306. This delivery of PFE can induce the regeneration of cochlear hair cells. In some examples, PFE can induce the repositioning of the cochlea 2304 by inducing apoptosis, killing diseased tissue around the cochlea and allowing healthy tissue to replace it. This can promote the health of cochlear hair cells within the cochlea 2304.

[0088] In some embodiments, the self-expanding mesh electrode 2300 is advanced within the mastoid air cell 2305, such that the self-expanding mesh electrode 2300 can eradicate infected tissue by delivering the PFE. The PFE procedure can be performed as a standalone procedure, but can also be combined with another procedure, wherein the PFE mesh electrode 2300 is activated after the completion of the other procedure. For example, drilling can be performed in the mastoid air cell 2305 to remove diseased tissue, or to open an infected mastoid air cell. In some cases, the PFE can be delivered after the mastoid cells have been opened to ensure the eradication of bacteria and infection. If bacteria are trapped within a biofilm, the PFE can be used to disrupt the biofilm matrix and kill the bacteria. The self-expanding mesh electrode 2300 can be applied within the tympanic membrane 2303 or within the external ear 2301, including the ear canal 2312, for the treatment of chronic otitis externa and chronically infected ear canals.

[0089] Now for reference Figure 24 The PFE delivery device can deliver the PFE to target tissues, such as tissues within the frontal sinus 2400, tissues within the maxillary sinus 2401, and tissues within other anatomical spaces. In some embodiments, similar to Figures 10A-10B The PFE delivery device 200 depicted in the image, and the console 100 can deliver the PFE (e.g., using...) Figures 1-2 The PFE generator 130) is delivered to Figure 24 The PFE delivery device 200 depicted is used to treat the tissue of the maxillary sinus 2401. Alternatively or alternatively, Figure 24 The frontal sinus 2400 depicted can be accessed by the PFE delivery device 200 to deliver PFE treatment to the tissue within the frontal sinus 2400.

[0090] In some embodiments, the PFE delivery device 200 includes one or more PFE electrodes, which can be used in a manner similar to... Figure 6CThe electrodes 211 are configured in a manner that allows for various delivery methods. For example, the delivery device 200 may include a set of four PFE electrodes 2403a-2403d (collectively referred to as “electrodes 2403”), some of which are positive and some of which are negative. In some embodiments, electrodes 2403a and 2403c may be positive and electrodes 2403b and 2403d may be negative. In some embodiments, electrodes 2403a and 2403c may be negative and electrodes 2403b and 2403d may be positive. In both embodiments, electrodes 2403 may alternate between positive and negative polarities. In some embodiments, some of the electrodes 2403 may be positive while the others are negative, such that the polarities are reversed to deliver bipolar PFE. In some embodiments, all electrodes 2403 may be configured to alternate between positive and negative polarities simultaneously, thus synchronizing the electrodes to deliver unipolar PFE.

[0091] PFE delivery to the paranasal sinuses, particularly the frontal sinus 2400 and maxillary sinus 2401, can eliminate or significantly reduce sinus mucosal thickening. Mucosal thickening can refer to the thickening of the lining of the sinus cavity (e.g., as...). Figure 24 The thickness of the mucosa 2402 of the cavity of the maxillary sinus 2401 is depicted. In some examples, PFE can reduce inflammation of the mucosa 2402 (leading to mucosal thickening) caused by infection, allergies, or chronic sinusitis. By reducing the thickened mucosa, PFE can result in improved airflow through the sinus openings, thereby helping to improve or eliminate symptoms such as nasal congestion, facial pain, infection, and pressure, because PFE treatment within the sinuses can spread to adjacent cavities such as the nasal cavity 2404, which may include an extension of the same mucosa 2402 lining the maxillary sinus 2401.

[0092] Now for reference Figure 25 In embodiments of the PFE delivery device 200, the distal tip 2500 can be bent such that the PFE electrode located at the distal tip 2500 is directed toward the patient's olfactory system 2501. In some examples, the olfactory system 2501 is located above the nasal turbinate 2502. Bending the distal tip 2500 allows it to be closer to the olfactory system 2501 (e.g., the olfactory bulb) compared to examples where the distal tip 2500 is not bent. When the generator 130 is activated (as described above)... Figures 1-2 As explained, the distal tip 2500 of the PFE delivery device 200 can deliver PFE therapy to the target tissue in a manner that triggers apoptosis, thereby replacing defective cells with healthy cells.

[0093] In some examples, the PFE delivery device 200 includes an actuator mechanism that allows a user to bend the distal tip 2500 of the PFE delivery device 200. For example, this actuator mechanism may include a knob, switch, slider, or any other type of actuator mechanism that bends the distal tip 2500 relative to the longitudinal axis of the PFE delivery device 200. In some cases, the PFE delivery device 200 may include a pull cable attached to the distal end of the PFE delivery device 200. When the pull cable is taut, it can bend the distal tip 2500 of the PFE delivery device 200.

[0094] In some embodiments, regions of the olfactory system include faulty cells that can contribute to abnormal neural activity. This abnormal neural activity can lead to impaired or complete loss of smell due to neural degeneration, surrounding tissue degeneration, or environmental triggers, including strong odors, exposure to cold air, alcohol intake, and / or spicy foods. Signals generated by neural networks within the olfactory bulb can cause anosmia, migraines, and / or other conditions. In some embodiments, the distal tip 2500 can deliver PFE to replace and regenerate cells through apoptosis and / or nerve stimulation. This can lead to neural improvement and restore nerves and other tissues within the olfactory system to their normal function, thereby improving smell, taste, and other conditions, such as migraines that may be caused by abnormal neural activity and / or other diseased tissues present in the region.

[0095] Now for reference Figure 26 Some embodiments of system 10 involve a PFE delivery device 200, which includes an elongated shaft 205 and a distal tip 204 (e.g., as shown in the image). Figures 6A-6C As described in [the text], it is used to treat the retropalatal, retrolingual, and epiglottic regions of a patient's pharynx 2600. For example, the PFE delivery device 200 can be advanced into the pharyngeal region where airflow is obstructed by airway stenosis (e.g., airway narrowing). When the distal tip 204 is close to the target tissue in the pharynx 2600, the PFE delivery device 200 can deliver PFE via one or more PFE electrodes to treat the target tissue. Figure 26 The described PFE delivery device 200 may represent a set of user-controlled, selectively inflatable balloons (e.g., Figures 6A-6C An example of a balloon 211. Figure 26 The PFE delivery device 200 depicted may include Figures 6A-6C Any electrode embodiment depicted (e.g., electrodes 221a, 221b, 222).

[0096] In some examples, the dilation balloon 211 can be used in conjunction with one or more electrodes to dilate the patient's airway stenosis and deliver PFE treatment. In some embodiments, dilation and PFE delivery (e.g., using...) Figures 1-2The PFE generator 130 can occur simultaneously. In some embodiments, expansion can occur before PFE delivery. In some cases, other delivery tools can be used, such as those including basket electrodes (e.g., Figures 3-4 The delivery device 200 (with basket electrode 220) is configured to deliver PFE treatment only without expansion, allowing the PFE to induce apoptosis in the target treatment area to remove dead tissue and stimulate the target treatment area to regenerate healthy tissue to replace the dead tissue. In some examples, the PFE delivery device 200 can treat infected tissue within the throat 2600. Even when the PFE delivery device 200 is embedded within a biomembrane, it can deliver PFE to the target tissue to induce apoptosis in a way that kills bacteria. This can lead to lymphocyte migration to the target tissue, thereby releasing T and B cell types that can fight any remaining bacteria.

[0097] In some examples, such as Figures 10A-10B , Figure 23 , Figure 24 and Figure 25 The anatomical regions where PFE is delivered can be associated with migraine and headache triggers. For example, eliminating diseased tissue within the mastoid process, sinuses, or olfactory system can provide relief not only within the (multiple) anatomical structures where PFE is delivered, but also relief from migraine and headache attacks. In addition to eliminating congestion in the nose, sinuses, and other areas of the head and neck, PFE delivery can reduce headaches and migraine attacks. In some cases, patients can achieve additional relief by modulating and / or resetting neural interfaces and ion channels to normal activity, where triggers such as those from various antigens and pathogens do not induce migraine or headache attacks. This is because tissues interfaced with neural activity can revert to healthy, non-disease-prone tissue.

[0098] It should be understood that any one or more of the teachings, expressions, embodiments, examples, etc., described herein may be combined with any one or more of the other teachings, expressions, embodiments, examples, etc., described herein. Therefore, the embodiments described herein should not be viewed in isolation from each other. Various suitable ways in which the teachings of this document can be combined will be apparent in light of the teachings herein. These modifications and variations are intended to be included within the scope of the claims.

[0099] Various embodiments of the invention have been shown and described. Further adjustments to the methods and systems described herein can be made through appropriate modifications without departing from the scope of the invention. Therefore, the scope of the invention should be considered in accordance with the following claims and should be understood as not being limited to the details of the structures and operations shown and described in the specification and drawings.

Claims

1. A pulsed field electroporation (PFE) system, comprising: A nasal dilation device having a handle, an elongated shaft extending distally from the handle, and a treatment tip located at the distal end of the elongated shaft, the treatment tip having a dilation balloon and a PFE electrode, such that the treatment tip is configured to deliver PFE from the PFE electrode at nasal tissue dilated by the dilation balloon.

2. The system of claim 1, further comprising a PFE console configured to receive a connector of the nasal dilation device, the PFE console including a user interface display and a PFE generator configured to output a predefined pattern of electric field from the PFE electrodes to induce at least one of irreversible electroporation (IRE) and reversible electroporation (RE) at the nasal tissue.

3. The system according to claim 2, wherein, The nasal dilator includes a unique identifier attached to the connector, which can be read by the console.

4. The system according to claim 3, wherein, The PFE generator remains disabled, and in response to the console capturing the unique identifier of the nasal dilation device to confirm that the nasal dilation device is an authorized device, the console adjusts the PFE generator to the enabled state.

5. The system according to claim 4, wherein, The handle of the nasal dilator includes a PFE activation button to selectively activate the PFE electrode located at the treatment tip of the nasal dilator.

6. The system according to any one of claims 1 to 5, wherein, The elongated shaft of the nasal dilation device includes an inflatable lumen in fluid communication with the interior of the dilation balloon.

7. The system according to claim 6, wherein, The elongated shaft includes at least one fluid drug delivery lumen, which communicates with at least one drug delivery port at the treatment tip of the nasal dilation device, such that the treatment tip is configured to simultaneously dilate the nasal tissue, deliver PFE treatment from the PFE electrode at the nasal tissue, and deliver fluid drug or agent to the nasal tissue.

8. A system comprising: A PFE delivery device is configured to enter target tissue in the ear, nose, or throat and includes a treatment tip with an expandable PFE electrode to deliver PFE to the target tissue.

9. The system of claim 8 further includes a PFE console configured to receive a connector of the PFE delivery device, the PFE console including a PFE generator.

10. The system according to any one of claims 8 to 9, further comprising an endoscope configured to simultaneously enter the ear, nose, or pharynx with the PFE delivery instrument.

11. The system according to claim 10, wherein, The PFE console is configured to modify images of the ear, nose, or pharynx captured by the endoscope to include one or more treatment markers at detection locations along the target tissue, the detection locations being where the PFE electrodes deliver PFE treatment.

12. A method comprising: The slender shaft of a pulsed field electroporation (PFE) delivery device is inserted into the ear, nose, or throat, such that the adjustable PFE electrode at the treatment tip of the distal end of the PFE delivery device is adjacent to the target tissue. The PFE electrode is adjusted relative to the elongated axis to press the PFE electrode against the target tissue; Activate the PFE generator connected to the console of the PFE delivery device to output a predefined pattern of electric field from the PFE electrode, thereby inducing at least one of irreversible electroporation (IRE) and reversible electroporation (RE) at the target tissue.

13. The method of claim 12, further comprising: In response to receiving a communication at the console indicating that the PFE delivery device is authorized for use, the PFE generator is switched from a disabled state to an enabled state.

14. The method according to any one of claims 12 to 13, wherein, The PFE delivery device includes a handle, an elongated shaft extending distally from the handle, and a treatment tip located at the distal end of the elongated shaft, the treatment tip having an expansion balloon and the adjustable PFE electrode.

15. The method of claim 14, further comprising expanding the target tissue while delivering PFE treatment from the PFE electrode pressed against the target tissue.

16. The method according to any one of claims 14 to 15, wherein, The PFE delivery device includes a unique identifier fixed to the outer surface, which can be read by the console.

17. The method of claim 16, further comprising capturing the unique identifier using the user interface of the console.

18. The method of any one of claims 16 to 17, further comprising modifying the characteristics of the PFE output from the PFE electrode in response to the console detecting the type of the PFE delivery device from a captured unique identifier.

19. The method according to any one of claims 14 to 18, wherein, The handle of the PFE delivery device includes a PFE activation button to selectively activate the PFE electrode to deliver PFE therapy.

20. The method of any one of claims 12 to 19, further comprising delivering a fluid drug through at least one fluid drug delivery lumen of the elongated shaft, the at least one fluid drug delivery lumen being in communication with at least one drug delivery port at the treatment tip of the PFE delivery device, such that the treatment tip simultaneously delivers PFE treatment from the PFE electrode located at the target tissue and delivers the fluid drug to the target tissue.

21. A system comprising: A pulsed field electroporation (PFE) generator, the pulsed field electroporation generator being configured to output pulsed PFE; A touchscreen interface coupled to the generator, the touchscreen interface being configured to receive user input to control the PFE characteristics output from the generator; and PFE delivery device, the PFE delivery device including an elongated shaft and a PFE electrode, the PFE electrode being adjustable relative to the elongated shaft to deliver the PFE from the PFE generator to at least one of the Eustachian tube, paranasal sinus, middle ear, mastoid tissue and sinus cavity.

22. The system according to claim 21, wherein, The PFE output from the PFE generator comprises a high-frequency waveform of 400 kHz to 10 MHz modulated by a lower frequency signal of 1 Hz to 400 kHz to deliver neural stimulation to nerves near the PFE electrodes.

23. The system according to any one of claims 21 to 22, wherein, The PFE output from the PFE generator comprises a burst of a high-amplitude waveform greater than 800V with a short-duration pulse of less than 5 microseconds to induce apoptosis in target tissue near the PFE electrode.

24. The system according to any one of claims 21 to 23, wherein, The PFE output from the PFE generator includes a single-phase waveform.

25. The system according to any one of claims 21 to 24, wherein, The PFE output from the PFE generator includes a biphase waveform.

26. The system according to any one of claims 21 to 25, wherein, The PFE output from the PFE generator includes alternating positive and negative amplitudes to reduce muscle stimulation.

27. The system according to any one of claims 21 to 26, wherein, The PFE output from the PFE generator includes a PFE waveform with a repetitive pattern to provide negative polarity bias energy in the absence of muscle contraction, the repetitive pattern including a single negative pulse, a single positive pulse, and a single negative pulse.

28. The system according to any one of claims 21 to 27, wherein, The PFE output from the PFE generator includes a PFE waveform with a repetitive pattern to provide positive polarity bias energy in the absence of muscle contraction, the repetitive pattern including a single positive pulse, a single negative pulse, and a single positive pulse.

29. The system according to any one of claims 21 to 28, wherein, The PFE delivery device includes a dilation tool configured to treat eustachian tube dysfunction by dilating the eustachian tube.

30. The system according to claim 29, wherein, The PFE delivery device is configured to simultaneously dilate the Eustachian tube and output the PFE from the PFE electrode to treat Eustachian tube dysfunction.

31. The system according to any one of claims 21 to 30, wherein, The PFE delivery device includes an expansion tool configured to treat chronic sinusitis by dilating the sinus ostium.

32. The system according to claim 31, wherein, The PFE delivery device is configured to simultaneously dilate the sinus ostium and output the PFE from the PFE electrode to treat chronic sinusitis.

33. The system according to any one of claims 21 to 32, wherein, The PFE delivery device is configured to extend via a nasal passage into intracranial tissue, such that the PFE electrode delivers the PFE to the intracranial tissue.

34. The system according to any one of claims 21 to 33, wherein, The PFE delivery device is configured to extend via a nasal passage into one or more sinus cavities, such that the PFE electrode delivers the PFE into the one or more sinus cavities.

35. A method using a pulsed field electroporation (PFE) device, comprising: The treatment tip of the PFE device is advanced into the subject's body, so that the PFE electrode along the treatment tip is close to the target site. as well as A PFE waveform is output from the PFE electrode at the treatment tip to induce apoptosis at the target site.

36. A pulsed field electroporation (PFE) method for treating target tissues of the ear, nose, or pharynx without general anesthesia, comprising: The PFE electrode is pressed against the target tissue, and a PFE waveform is output from the PFE electrode.

37. The method of claim 36, further comprising expanding the expansion tool against the target tissue.

38. A method for delivering a pulsed field electroporation (PFE) waveform to target tissue of the ear, nose, or pharynx without inducing necrosis at the target tissue, comprising: Advance the treatment tip of the PFE device so that the PFE electrode along the treatment tip is close to the target tissue of the ear, nose or throat. as well as A PFE waveform is output from the PFE electrode at the treatment tip to induce apoptosis of cells located in the target tissue.

39. A system comprising a pulsed field electroporation (PFE) delivery device configured to both dilate target tissue and output PFE from a PFE electrode proximate to the target tissue.

40. The system according to claim 39, wherein, By delivering the PFE, the PFE delivery device kills bacteria within the biofilm matrix.

41. The system according to any one of claims 39 to 40, wherein, By delivering the PFE, the PFE delivery device reduces mucosal thickening in one or more sinus cavities.

42. The system according to any one of claims 39 to 41, wherein, By delivering the PFE, the PFE delivery device triggers an immune response in one or more sinus cavities.

43. The system according to any one of claims 39 to 42, wherein, By delivering the PFE, the PFE delivery device reduces or eliminates sinus infection in one or more sinus cavities.

44. The system according to any one of claims 39 to 43, wherein, The PFE delivery device is configured to deliver the PFE from the PFE electrode to the cochlear tissue and nerve fibers, and wherein, by delivering the PFE, the PFE delivery device triggers a regeneration process of cochlear hair cells within the cochlea.

45. The system according to any one of claims 39 to 44, wherein, The PFE delivery device is configured to deliver the PFE to a patient's olfactory system, and wherein, by delivering the PFE, the PFE delivery device regenerates olfactory tissue to improve the patient's sense of smell.

46. ​​The system according to any one of claims 39 to 45, wherein, The PFE delivery device is configured to deliver the PFE to a patient's olfactory system, and wherein, by delivering the PFE, the PFE delivery device reduces or eliminates infection within the olfactory system.

47. The system according to any one of claims 39 to 46, wherein, The PFE delivery device is configured to deliver the PFE to a patient’s olfactory system, and wherein, by delivering the PFE, the PFE delivery device stimulates the olfactory bulb of the olfactory system.

48. The system according to any one of claims 39 to 47, wherein, The PFE delivery device is configured to deliver the PFE to a patient's mastoid tissue, and wherein, by delivering the PFE, the PFE delivery device is configured to elicit an immune response in the mastoid tissue.

49. The system according to any one of claims 39 to 48, wherein, The PFE delivery device is configured to deliver the PFE to a patient's mastoid tissue, and wherein, by delivering the PFE, the PFE delivery device is configured to reduce or eliminate infection in the mastoid tissue.

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