Devices and systems for delivering fluid to the inner ear

Abstract

Embodiments of the present disclosure include devices, systems, and methods for delivering fluid to the inner ear. The device (10) for delivering fluid to the ear includes a handle portion (12) including a proximal end and a distal end, a needle subassembly (26) coupled to the distal end of the handle portion (12) and including a curved needle (38), and a tube (36) coupled to the proximal end of the handle portion (12). The curved needle (38) extends through the handle portion (12) and is in direct fluid connection with the tube (36).

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims priority and benefit to U.S. Provisional Patent Application Nos. 63 / 030,519 (filed May 27, 2020), 63 / 126,270 (filed Dec. 16, 2020), and 63 / 151,610 (filed Feb. 19, 2021), all of which are entitled "DEVICES, SYSTEMS, AND METHODS FOR DELIVERING FLUID TO THE INNER EAR", the disclosures of which are hereby incorporated by reference in their entirety.

Background Art

[0002] Delivery of therapeutic agents to the inner ear presents significant challenges. The associated organs are deeply buried within the skull, encased in bone, and isolated from the circulatory system by the blood - labyrinth barrier. Some of the inner ear organs, including the organ of Corti, are particularly inaccessible and fragile.

[0003] A liquid containing a therapeutic agent can be delivered to the middle ear cavity with the expectation that it will diffuse across the round window membrane (RWM) into the inner ear. However, only a small fraction of the administered fluid and therapeutic agent actually enters the fluid space of the inner ear. Distribution throughout the inner ear generally relies on simple diffusion, by which the delivered fluid and therapeutic agent are highly diluted by the time they reach the target site of action in the inner ear.

Summary of the Invention

Means for Solving the Problems

[0004] Embodiments of this disclosure include devices, systems, and methods for delivering fluids to the inner ear. The devices, systems, and methods described herein include devices for administering fluids into the perilymph of the inner ear. In some embodiments, the devices, systems, and methods described offer potential advantages over available devices, systems, and methods with respect to both the safety and efficacy of the therapeutic fluids administered via the intracochlear pathway.

[0005] In some embodiments, the design elements of the devices and systems described include maintaining the sterility of the injected fluid, minimizing air bubbles introduced into the inner ear, the ability to accurately deliver small amounts at a controlled flow rate (e.g., when combined with the use of a standard pump), allowing the surgeon to visualize the round window membrane (RWM) during delivery through the ear canal, minimizing damage to the RWM or inner ear structures beyond the RWM, and minimizing leakage of the test material through the RWM.

[0006] In one embodiment, the Disclosure provides a device for delivering fluid to the ear, the device comprising a handle portion including a proximal and distal end, a needle subassembly coupled to the distal end of the handle portion and including a curved needle, and a tube coupled to the proximal end of the handle portion. The curved needle extends through the handle portion and is directly fluid-connected to the tube.

[0007] In some embodiments, the device includes a retractable support coupled to the proximal end of the needle subassembly.

[0008] In some embodiments, the distal end of the handle is coupled to the proximal end of the telescopic support.

[0009] In some embodiments, the expandable support includes a plurality of nesting hypotubes.

[0010] In some embodiments, the curved needle includes an inclined tip for piercing at least one membrane, and a bent portion.

[0011] In some embodiments, the device includes a tension-relieving mechanism coupled to the proximal end of the handle portion.

[0012] In some embodiments, the device includes a camera (e.g., a distal tip camera). The distal tip camera is located within the needle subassembly.

[0013] In some embodiments, the tube is coupled to the curved needle inside the hollow part of the handle.

[0014] In some embodiments, the device includes an inner diameter of approximately 0.005 inches to approximately 0.01 inches.

[0015] In some embodiments, the bent portion has a length of about 0.5 mm to about 5 mm (for example, about 1 mm to about 3 mm, for example, about 1.4 mm).

[0016] In some embodiments, the angle is approximately 20 degrees to approximately 70 degrees (for example, approximately 20 degrees to approximately 60 degrees, for example, approximately 20 degrees to approximately 50 degrees, for example, approximately 20 degrees to approximately 40 degrees, for example, approximately 30 degrees, for example, approximately 30 degrees to approximately 70 degrees, for example, approximately 40 degrees to approximately 60 degrees, for example, approximately 55 degrees).

[0017] In some embodiments, the angle is approximately 30 degrees.

[0018] In some embodiments, the angle is approximately 55 degrees.

[0019] In some embodiments, the curved needle includes gauges in the range of about 10 to about 35, for example, about 20 to about 35, for example, about 30 to about 35, for example, 33 gauge.

[0020] In some embodiments, the curved needle is made of stainless steel, at least partially.

[0021] In some embodiments, the device includes adhesives placed at the proximal and distal ends of the handle portion.

[0022] In some embodiments, the device includes a stopper coupled to a curved needle. The stopper is positioned within the inner ear and is shaped and sized to control the distance that the angled tip projects into the cochlea.

[0023] In some embodiments, the stopper includes a cylindrical disk type.

[0024] In some embodiments, the stopper is formed in place on the curved needle, and the stopper prevents the curved needle from being inserted into at least one membrane beyond a desired amount.

[0025] In some embodiments, the stopper is positioned at a distance of about 0.2 mm to about 1.2 mm (e.g., about 0.4 mm to about 1.0 mm, e.g., about 0.6 mm to about 0.9 mm, e.g., about 0.85 mm) from the tip of the angled tip.

[0026] In some embodiments, the stopper includes a diameter of about 0.2 mm to about 1.2 mm (e.g., about 0.4 mm to about 1.0 mm, e.g., about 0.6 mm to about 0.9 mm, e.g., about 0.85 mm).

[0027] In some embodiments, the stopper includes a height of about 0.2 mm to about 1.0 mm (e.g., about 0.3 mm to about 0.7 mm, e.g., about 0.4 mm to about 0.6 mm, e.g., about 0.5 mm).

[0028] In some embodiments, each hypodermic tube of the plurality of nested hypodermic tubes includes a gauge of about 10 to about 30 (e.g., 14XH, 20TW, 23XTW, and / or 27TW).

[0029] In some embodiments, each hypodermic tube of the plurality of nested hypodermic tubes includes stainless steel.

[0030] In some embodiments, the handle portion further includes a tip located at the distal end of the handle, and the telescopic support is coupled to the tip. The handle tapers toward the first distal end (for example, so that the second proximal end of the telescopic support is coupled to the first distal end).

[0031] In some embodiments, the expandable support tapers from an outer diameter of about 0.2 inches or less at the proximal end to an outer diameter of about 0.01 inches or more at the distal end.

[0032] In some embodiments, the handle portion includes machined grooves for tactile feedback and control.

[0033] In some embodiments, the handle portion is molded and sized to facilitate placement in the inner ear.

[0034] In some embodiments, the tension relief mechanism includes a layered extruded material (e.g., a layered Pebax extruded material).

[0035] In some embodiments, a tension-relieving mechanism prevents twisting and / or deformation of the tube.

[0036] In some embodiments, the tube is joined to the curved needle by compression fitting.

[0037] In some embodiments, the tube contains polyetheretherketone (PEEK).

[0038] In some embodiments, the tube has an inner diameter of about 0.003 inches to about 0.01 inches (for example, about 0.007 inches).

[0039] In some embodiments, the tube has an outer diameter of approximately 1 / 64 inch to approximately 1 / 16 inch (for example, approximately 1 / 32 inch).

[0040] In some embodiments, the tube includes lengths greater than 20 inches, for example, greater than 30 inches, for example, greater than 40 inches, for example, greater than 50 inches, for example, greater than 60 inches, for example, about 60 inches.

[0041] In some embodiments, the device is sterile and / or biocompatible.

[0042] In some embodiments, the inclined tip protrudes from the bend of the curved needle to form an outlet for distributing fluid.

[0043] In another aspect, the disclosure provides a system comprising a device and a sterile syringe fluid-coupled to a tube.

[0044] In some embodiments, the system includes a pump.

[0045] In some embodiments, the pump is pumped at a rate of (for example, approximately 10 μL / min to approximately 60 μL / min, for example, approximately 15 μL / min to approximately 55 μL / min, for example, approximately 20 μL / min to approximately 50 μL / min, for example, approximately 25 μL / min to approximately 45 μL / min, for example, approximately 25 μL / min to approximately 40 μL / min, for example, approximately 20 μL / min to approximately 35 μL / min, for example, approximately 30 μL / min) (for example, approximately 10 μL / min to approximately 200 μL / min, for example, approximately 20 μL / min to approximately 180 μL / min) Control the flow rate of fluid through one of the devices (at a rate of L / min, for example, approximately 30 μL / min to approximately 180 μL / min, for example, approximately 40 μL / min to approximately 150 μL / min, for example, approximately 50 μL / min to approximately 150 μL / min, for example, approximately 60 μL / min to approximately 140 μL / min, for example, approximately 70 μL / min to approximately 130 μL / min, for example, approximately 80 μL / min to approximately 120 μL / min, for example, approximately 90 μL / min to approximately 110 μL / min, for example, approximately 100 μL / min).

[0046] In some embodiments, the stopper is seated around a stopper fixing groove located within the curved needle.

[0047] In some embodiments, the device includes an annular brace positioned on the contact surface between the retractable support and the handle portion.

[0048] In some embodiments, the device includes at least one machined barb located at the proximal end of the handle portion.

[0049] In some embodiments, the machined barb interfaces with a tension relief mechanism to prevent axial movement between the handle and the tension relief mechanism.

[0050] In another aspect, the Disclosure provides a delivery system comprising: a delivery device including a distal end and a stopper located at the distal end of the delivery device; a distal end camera located at the distal end of the delivery device, the distal end camera including an image sensor; and a monitor operably coupled to the distal end camera. The monitor displays information received from the distal end camera.

[0051] In some embodiments, the stopper is transparent.

[0052] In some embodiments, the stopper includes a transparent section for the distal end camera to view through the stopper.

[0053] In some embodiments, the distal end camera is positioned above the front of the stopper, with the front of the stopper facing the target.

[0054] In some embodiments, the target is a part of the ear.

[0055] In some embodiments, the distal end camera is embedded (e.g., integrated) within a stopper.

[0056] In some embodiments, the distal end camera is positioned behind the stopper.

[0057] In some embodiments, the delivery system includes a wire that is operably coupled between the distal end camera and the monitor.

[0058] In some embodiments, the distal end camera includes an autofocus function.

[0059] In some embodiments, the distal tip camera includes at least one of the following shapes: rectangular, tip-shaped, cylindrical, and combinations thereof.

[0060] In some embodiments, the image sensor includes a field of view of approximately 90° to approximately 150°.

[0061] In some embodiments, the image sensor includes a rectangular parallelepiped shape with dimensions up to 10 mm × 10 mm and a height up to 100 mm, and / or a cylindrical shape with an outer diameter up to 10 mm and a length up to 100 mm.

[0062] In some embodiments, the image sensor includes an image array capable of capturing video with a resolution of at least 10x10 pixels at a frame rate of at least 5 frames per second (fps).

[0063] In some embodiments, the image sensor includes an image area of ​​up to 10 mm x 10 mm.

[0064] In some embodiments, the image sensor includes an optical format of up to 10 mm and a pixel size of up to 10 μm.

[0065] In some embodiments, the delivery system includes a processor operably coupled to the image sensor.

[0066] In some embodiments, the delivery system includes a driver package and / or a software package.

[0067] In some embodiments, the delivery system includes at least one light source.

[0068] In some embodiments, the delivery system includes optical fibers.

[0069] In another embodiment, the Disclosure provides a distal tip camera system comprising: an image sensor positioned at the distal end of a needle including a stopper; a wire operably coupled to the image sensor; a processor operably coupled to the image sensor; and a monitor operably coupled to the processor for displaying information captured by the image sensor and processed by the processor.

[0070] In another aspect, the Disclosure provides a surgical procedure for delivering a therapeutic fluid to a portion of the inner ear (for example, using one of the devices disclosed herein), the surgical procedure comprising deploying the posterior tympanic membrane flap, creating an opening in the stapes footplate, piercing a round window with a needle positioned at the distal end of a fluid delivery device, positioning the fluid delivery device at a desired insertion depth within the round window, and delivering the therapeutic fluid to the inner ear by the fluid delivery device.

[0071] In some embodiments, the procedure includes activating a distal tip camera, endoscope, and / or surgical microscope before piercing the circular window, and monitoring the flow rate and / or distribution of the therapeutic fluid traversing the inner ear using the distal tip camera, endoscope, and / or surgical microscope before piercing the circular window.

[0072] In some embodiments, the procedure includes activating the distal tip camera before piercing the circular window. The distal tip camera is communicatively coupled to at least one monitor that the surgeon can view during the procedure.

[0073] In some embodiments, deploying the posterior tympanic valve involves cutting the posterior tympanic valve using a microcurette and / or drill.

[0074] In some embodiments, the procedure includes pre-treating and draping the ear before deploying the posterior tympanic membrane valve, positioning the patient before pre-treating and draping the ear, inducing anesthesia before positioning the patient, and marking the ear before inducing anesthesia.

[0075] In some embodiments, the procedure includes connecting a tube between the fluid delivery device and the upstream pump before deploying the posterior tympanic valve, sterilizing the fluid delivery device before deploying the posterior tympanic valve, and priming the system before deploying the posterior tympanic valve.

[0076] In some embodiments, the therapeutic solution comprises at least one viral gene therapy.

[0077] In some embodiments, the procedure includes delivering a therapeutic fluid through a fluid delivery device, then removing the fluid delivery device from the inner ear, and after removal of the fluid delivery device, applying at least one skin treatment to the round window membrane and / or stapes base plate.

[0078] In some embodiments, the procedure includes applying at least one skin treatment followed by returning the posterior tympanic membrane valve to its original position.

[0079] In some embodiments, the procedure includes deploying the posterior tympanic membrane flap and then removing bone and / or pseudomembrane protrusions from the junction of the bony canal and the tympanic membrane.

[0080] In some embodiments, the procedure includes removing bone using a diamond drill and / or an otological drill.

[0081] In some embodiments, creating an opening in the stapes footplate involves using a laser to create an opening in the stapes footplate.

[0082] In some embodiments, the laser includes an otological laser.

[0083] In some embodiments, the procedure includes applying at least one of anesthesia and adrenaline to the patient's external auditory canal before deploying the posterior tympanic membrane valve.

[0084] In some embodiments, ear pretreatment further includes applying at least one disinfectant to the ear.

[0085] In some embodiments, the disinfectant includes povidone-iodine, iodopovidone, betadine, vocadine, and / or piodin.

[0086] In some embodiments, the skin treatment comprises sodium hyaluronate and / or hyaluronic acid.

[0087] In another aspect, the Disclosure provides a method for delivering a therapeutic fluid to a portion of the inner ear (for example, using any one of the devices or systems disclosed herein), the method comprising: creating an opening in the stapes base plate; piercing a circular window with a needle positioned at the distal end of a fluid delivery device; positioning the fluid delivery device at a desired insertion depth within the circular window; and delivering the therapeutic fluid into the inner ear by the fluid delivery device. The therapeutic fluid comprises at least one viral gene therapy.

[0088] In another aspect, the Disclosure provides a method for delivering a therapeutic fluid to a portion of the inner ear (for example, using any one of the devices or systems disclosed herein), the method comprising: creating an opening in the stapes base plate; piercing a round window with a needle positioned at the distal end of a fluid delivery device; positioning the fluid delivery device at a desired insertion depth within the round window; and delivering the therapeutic fluid into the inner ear by the fluid delivery device. The desired insertion depth includes a depth of about 0.7 mm to about 1.0 mm.

[0089] In some embodiments, delivering the therapeutic fluid into the inner ear by a fluid delivery device involves delivering the therapeutic fluid at a flow rate of approximately 20 μL / min to approximately 100 μL / min.

[0090] In some embodiments, delivering the therapeutic fluid into the inner ear by a fluid delivery device involves delivering a total volume of therapeutic fluid ranging from about 0.07 mL to about 0.11 mL.

[0091] In some embodiments, delivering a therapeutic fluid to the inner ear by a fluid delivery device involves delivering the therapeutic fluid for a duration ranging from about 1 minute to about 5 minutes.

[0092] In another embodiment, the Disclosure provides a device for delivering fluid to the ear, the device comprising a handle portion including a proximal and distal end; a retractable support coupled to the distal end of the handle portion; a needle subassembly, comprising a curved needle, coupled to the distal end of the retractable support; and a tube coupled to the proximal end of the handle portion.

[0093] In another embodiment, the disclosure provides a packaging system for holding a delivery device, including a distal end and a stopper positioned at the distal end of the delivery device. The packaging system includes a mounting surface and a device nest for holding the delivery device. The device nest is mounted on the mounting surface.

[0094] In another embodiment, the disclosure provides a packaging system for holding a delivery device, the packaging system including a mounting surface and a device nest for holding the delivery device. The device nest is mounted on the mounting surface.

[0095] In some embodiments, the system includes at least one pair of oppositely oriented slits located within the mounting surface.

[0096] In some embodiments, a pair of oppositely oriented slits hold a fluid-coupled tube to the proximal end of the delivery device.

[0097] In some embodiments, the system includes a plurality of nested notches located within a device nest, each nested notch holding at least one of the proximal end, distal end, and body of the delivery device.

[0098] In some embodiments, the system includes at least one mounting slit located within the mounting surface, and at least one locking portion extending across the device nesting portion and attached to the mounting slit.

[0099] In some embodiments, the device nesting portion is fiddle-shaped.

[0100] In some embodiments, the system includes at least one twist tie for securing the delivery device to the device nest.

[0101] In some embodiments, the pair of oppositely oriented slits include a pair of curved ends at either end to prevent the pair of oppositely oriented slits from damaging the mounting surface.

[0102] In some embodiments, the delivery device includes a device body including a distal tip and a proximal tip, and a tube fluidly coupled to the proximal tip.

[0103] In another embodiment, the Disclosure provides a packaging system for holding a delivery device used to deliver a therapeutic fluid to the inner ear, the packaging system comprising a mounting surface and a device nest for holding the delivery device. The device nest is mounted on the mounting surface.

[0104] In some embodiments, the system includes a PEEK tube fluidly coupled upstream of a delivery device and a sleeve positioned around the PEEK tube.

[0105] In some embodiments, the system includes sleeves arranged concentrically around the tube to prevent the tube from twisting.

[0106] In some embodiments, the sleeve is made of a polymer material.

[0107] In another aspect, the Disclosure provides a surgical procedure for delivering a therapeutic fluid to a portion of a patient's inner ear, the surgical procedure including injecting the therapeutic fluid into the inner ear using a delivery device as described herein.

[0108] In some embodiments, the surgical procedure includes performing a transtubal tympanotomy, performing a laser-assisted microstapes osteotomy, and injecting a therapeutic fluid into the inner ear using a delivery device as described herein.

[0109] In some embodiments, the surgical procedure includes performing a transcanal tympanotomy, performing a laser-assisted microstapes osteotomy, injecting a therapeutic fluid into the inner ear using a delivery device described herein, applying a occlusive agent around the patient's round window and / or oval window, and lowering the patient's tympanostomy flap to its anatomical position.

[0110] In some embodiments, the surgical procedure includes performing a transcanal tympanotomy, pre-treating the patient's round window, performing a laser-assisted microstapes osteotomy, pre-treating both the delivery device and the therapeutic fluid described herein for delivery to the inner ear, injecting the therapeutic fluid into the inner ear using the delivery device, applying a occlusive agent around the patient's round window and / or oval window, and lowering the patient's tympanostomy flap to its anatomical position.

[0111] In some embodiments, performing laser-assisted microstapes osteotomy includes using a KTP otological laser and / or a CO2 otological laser.

[0112] In some embodiments, the therapeutic solution includes an AAV vector. In some embodiments, the AAV vector is an Anc80AAV vector. In some embodiments, the AAV vector includes a coding region that encodes hOTOF.

[0113] Throughout the description, where a device, system, procedure, and / or method is described as having, including, or comprising certain components, or where a method is described as having, including, or comprising certain steps, it is intended that there exist devices, systems, procedures, and / or methods of the disclosure that essentially consist of or comprise the enumerated components, and that there exist methods of the disclosure that essentially consist of or comprise the enumerated processing steps.

[0114] It should be understood that the order of steps or the order in which specific actions are performed is not important, as long as this method works. Furthermore, two or more steps or actions can be performed simultaneously.

[0115] The following description is for illustrative purposes only and is not intended to limit the disclosure to any specific embodiment described.

[0116] References made herein in any publication, for example in the background section, do not constitute an endorsement that the publication is a substitute for the prior art relating to any of the claims of the present invention. The background section is presented for clarity and does not constitute a description of the prior art relating to any of the claims.

[0117] A complete and effective disclosure of embodiments of this disclosure, including the best mode, directed to those skilled in the art, is described in the specification with reference to the accompanying drawings. The present invention provides, for example, the following: (Item 1) A device for delivering fluid to the ear, A handle portion including the proximal and distal ends, A needle subassembly coupled to the distal end of the handle portion, the needle subassembly including a curved needle, The handle portion comprises a tube connected to the proximal end, The device wherein the curved needle extends through the handle portion and is directly fluid-connected to the tube. (Item 2) The device according to item 1, further comprising a retractable support coupled to the proximal end of the needle subassembly. (Item 3) The device according to items 1 and 2, wherein the distal end of the handle is coupled to the proximal end of the retractable support. (Item 4) The device according to item 2 or 3, wherein the expandable support comprises a plurality of nesting hypotubes. (Item 5) The aforementioned curved needle is An angled tip for piercing at least one membrane, The bent part, A device, including any one of the preceding items. (Item 6) The device according to any one of the preceding items, comprising a tension-relaxing mechanism coupled to the proximal end of the handle portion. (Item 7) The device according to any one of the preceding items, comprising a camera (for example, a distal tip camera, the distal tip camera being located within the needle subassembly). (Item 8) The tube is coupled to the curved needle inside the hollow interior of the handle portion, as described in any one of the preceding items. (Item 9) The tube is the device described in item 8, having an inner diameter of approximately 0.005 inches to approximately 0.01 inches. (Item 10) The device according to any one of the preceding items, wherein the bent portion has a length of approximately 0.5 mm to approximately 5 mm (for example, approximately 1 mm to approximately 3 mm, for example, approximately 1.4 mm). (Item 11) The device described in any one of the preceding items, wherein the angle is approximately 20 degrees to approximately 70 degrees (for example, approximately 20 degrees to approximately 60 degrees, for example, approximately 20 degrees to approximately 50 degrees, for example, approximately 20 degrees to approximately 40 degrees, for example, approximately 30 degrees, for example, approximately 30 degrees to approximately 70 degrees, for example, approximately 40 degrees to approximately 60 degrees, for example, approximately 55 degrees). (Item 12) The aforementioned angle is approximately 30 degrees, as described in any one of the preceding items. (Item 13) The aforementioned angle is approximately 55 degrees, as described in any one of the preceding items. (Item 14) The curved needle is a device according to any one of the preceding items, including gauges in the range of about 10 to about 35, for example, about 20 to about 35, for example, about 30 to about 35, for example, 33 gauge. (Item 15) The aforementioned curved needle is made of stainless steel, as described in any one of the preceding items. (Item 16) The device according to any one of the preceding items, comprising adhesive disposed at the proximal and distal ends of the handle portion. (Item 17) The curved needle is equipped with a stopper, The device according to any one of the preceding items, wherein the stopper is positioned within the inner ear and is shaped and sized to control the distance the inclined tip protrudes into the cochlea. (Item 18) The stopper is a device as described in any one of the preceding items, including a cylindrical disc type. (Item 19) The stopper is molded to fit the curved needle appropriately. The device according to any one of the preceding items, wherein the stopper prevents the curved needle from being inserted into at least one membrane by a desired amount. (Item 20) The device according to any one of the preceding items, wherein the stopper is positioned at a distance of approximately 0.2 mm to approximately 1.2 mm (for example, approximately 0.4 mm to approximately 1.0 mm, for example, approximately 0.6 mm to approximately 0.9 mm, for example, approximately 0.85 mm) from the distal end of the inclined tip. (Item 21) The stopper is a device as described in any one of the preceding items, having a diameter of approximately 0.2 mm to approximately 1.2 mm (for example, approximately 0.4 mm to approximately 1.0 mm, for example, approximately 0.6 mm to approximately 0.9 mm, for example, approximately 0.85 mm). (Item 22) The stopper is a device as described in any one of the preceding items, including a height of approximately 0.2 mm to approximately 1.0 mm (for example, approximately 0.3 mm to approximately 0.7 mm, for example, approximately 0.4 mm to approximately 0.6 mm, for example, approximately 0.5 mm). (Item 23) Each of the multiple nested hypotubes in the device described in item 4 includes approximately 10 to approximately 30 gauges (e.g., 14XH, 20TW, 23XTW, and / or 27TW). (Item 24) The device described in item 4, wherein each of the multiple nested hypotubes is made of stainless steel. (Item 25) The device according to any one of the preceding items, wherein the handle portion further includes a tip located at the distal end of the handle, the retractable support is coupled to the tip, and the handle tapers to a first distal end (for example, the second proximal end of the retractable support is coupled to the first distal end). (Item 26) The expandable support is the device described in any one of the preceding items, tapering from an outer diameter of approximately 0.2 inches or less at the proximal end to an outer diameter of approximately 0.01 inches or more at the distal end. (Item 27) The device according to any one of the preceding items, wherein the handle portion includes machined grooves for tactile sensation and control. (Item 28) The device according to any one of the preceding items, wherein the handle portion is molded and sized to facilitate placement in the inner ear. (Item 29) The tension-relaxing mechanism is a device according to any one of the preceding items, comprising a layered extruded material (e.g., a layered Pebax extruded material). (Item 30) The tension-relieving mechanism is a device according to any one of items 6 to 29, which prevents twisting and / or deformation of the tube. (Item 31) The device according to any one of items 8 to 30, wherein the tube is coupled to the curved needle by compression fitting. (Item 32) The tube comprises polyether ether ketone (PEEK), as described in any one of items 8 to 31. (Item 33) The tube is a device as described in any one of items 8 to 32, with an inner diameter of approximately 0.003 inches to approximately 0.01 inches (for example, approximately 0.007 inches). (Item 34) The tube is a device as described in any one of items 8 to 33, with an outer diameter of approximately 1 / 64 inch to approximately 1 / 16 inch (for example, approximately 1 / 32 inch). (Item 35) The tube includes a length greater than 20 inches, for example, greater than 30 inches, for example, greater than 40 inches, for example, greater than 50 inches, for example, greater than 60 inches, for example, a length of approximately 60 inches, as described in any one of items 8 to 34. (Item 36) The device is sterile and / or biocompatible, as described in any one of the preceding items. (Item 37) The device according to any one of the preceding items, wherein the inclined tip protrudes from the bent portion of the curved needle to form an outlet for distributing fluid. (Item 38) A system comprising the device described in any one of the preceding items and a sterile syringe fluid-coupled to the tube. (Item 39) A system as described in item 38, comprising a pump. (Item 40) The pump dispenses (for example, at speeds of approximately 10 μL / min to 60 μL / min, approximately 15 μL / min to 55 μL / min, approximately 20 μL / min to 50 μL / min, approximately 25 μL / min to 45 μL / min, approximately 25 μL / min to 40 μL / min, approximately 20 μL / min to 35 μL / min, approximately 30 μL / min) (for example, approximately 10 μL / min to 200 μL / min, approximately 20 μL / min to 180 μL / min, approximately 30 μL / min) The system described in item 39, which controls the flow rate of fluid through any one of the devices at a rate of L / min to approximately 180 μL / min, for example, approximately 40 μL / min to approximately 150 μL / min, for example, approximately 50 μL / min to approximately 150 μL / min, for example, approximately 60 μL / min to approximately 140 μL / min, for example, approximately 70 μL / min to approximately 130 μL / min, for example, approximately 80 μL / min to approximately 120 μL / min, for example, approximately 90 μL / min to approximately 110 μL / min, for example, approximately 100 μL / min. (Item 41) A delivery system, A delivery device, The distal end and A stopper positioned at the distal end of the delivery device, The delivery device comprises, A distal tip camera positioned at the distal end of the delivery device, comprising an image sensor, A monitor operably coupled to the distal end camera, which displays information received from the distal end camera, The delivery system is provided with the following: (Item 42) The stopper is transparent, as described in item 41. (Item 43) The system according to item 41, wherein the stopper includes a transparent portion for the distal end camera to view through the stopper. (Item 44) The system according to item 41, wherein the distal tip camera is positioned on the front surface of the stopper, and the front surface of the stopper is facing the target. (Item 45) The aforementioned target is part of the ear, as described in item 44. (Item 46) The distal end camera is embedded (e.g., integrated) within the stopper, as described in item 43. (Item 47) The distal end camera is positioned behind the stopper, as in the system described in item 43. (Item 48) The system according to item 41, further comprising a wire operably coupled between the distal end camera and the monitor. (Item 49) The distal end camera is equipped with an autofocus function, as described in item 41. (Item 50) The distal tip camera is included in the system according to item 41, wherein the distal tip camera is at least one of a rectangular parallelepiped shape, a tip shape, a cylindrical shape, and a combination thereof. (Item 51) The image sensor in the system described in item 41 includes a field of view of approximately 90° to approximately 150°. (Item 52) The system according to item 41, wherein the image sensor includes at least one of the following: a rectangular parallelepiped shape with dimensions of up to 10 mm x 10 mm and a height of up to 100 mm; and a cylindrical shape with an outer diameter of up to 10 mm and a length of up to 100 mm. (Item 53) The system according to item 41, wherein the image sensor includes an image array capable of capturing video with a resolution of at least 10 x 10 pixels at a frame rate of at least 5 frames per second (fps). (Item 54) The image sensor is the system described in item 41, which includes an image area of ​​up to 10 mm x 10 mm. (Item 55) The image sensor is the system described in item 41, comprising an optical format of up to 10 mm and a pixel size of up to 10 μm. (Item 56) The system according to item 41, comprising a processor operably coupled to the image sensor. (Item 57) The system described in item 41, including the driver package and / or software package. (Item 58) The system described in item 41, comprising at least one light source. (Item 59) A system as described in item 41, comprising optical fiber. (Item 60) A distal tip camera system, An image sensor positioned at the distal end of a needle, wherein the distal end of the needle is equipped with a stopper, and the image sensor and A wire operably coupled to the aforementioned image sensor, A processor operably coupled to the aforementioned image sensor, A monitor operably coupled to the processor for displaying information captured by the image sensor and processed by the processor, The distal tip camera system comprising the aforementioned. (Item 61) A surgical procedure for delivering a therapeutic fluid to a portion of the inner ear (for example, using one of the devices described in items 1-37 or 83, or one of the systems described in items 38-60), To deploy the posterior tympanic valve, Creating an opening in the stapes footplate, The process involves piercing a circular window with a needle positioned at the distal end of a fluid delivery device, Positioning the fluid delivery device at a desired insertion depth within the circular window, The fluid delivery device delivers the therapeutic fluid into the inner ear, The surgical procedure, including the aforementioned surgical procedure. (Item 62) Before inserting the circular window, activate at least one of the distal tip camera, endoscope, and surgical microscope. Before inserting the circular window, at least one of the flow rate of the treatment fluid traversing the inner ear and the distribution of the treatment fluid is monitored using at least one of the distal tip camera, the endoscope, and the surgical microscope. The measures described in item 61, further including the measures described in item 61. (Item 63) This includes activating the distal tip camera before piercing the circular window, The procedure according to item 62, wherein the distal end camera is communicably coupled to at least one monitor visible to the surgeon during the procedure. (Item 64) The procedure described in item 61, which involves deploying the posterior tympanic valve by cutting the posterior tympanic valve using at least one of a microcurette and a drill. (Item 65) Before deploying the posterior tympanic membrane valve, the ear is pre-treated and draped. Positioning the patient before pre-treating and draping the ears, Induce anesthesia before positioning the patient, Before inducing anesthesia, mark the ear, The measures described in item 61, further including the measures described in item 61. (Item 66) Before deploying the rear tympanic valve, connect the tube between the fluid delivery device and the upstream pump, Before deploying the posterior tympanic membrane valve, the fluid delivery device shall be sterilized. Before deploying the posterior tympanic valve, the system is primed, The measures described in item 61, further including the measures described in item 61. (Item 67) The treatment according to item 61, wherein the therapeutic solution comprises at least one viral gene therapy. (Item 68) After the treatment fluid has been delivered by the fluid delivery device, the fluid delivery device is removed from the inner ear. After removing the fluid delivery device, at least one skin treatment is applied to the membrane of the circular window and at least one of the stapes base plate. The measures described in item 61, further including the measures described in item 61. (Item 69) The procedure according to item 68, further comprising applying at least one skin treatment, followed by returning the posterior tympanic membrane valve to its original position. (Item 70) The procedure according to item 61, further comprising, after deploying the posterior tympanic membrane valve, removing bone and / or pseudomembrane protrusions from the junction of the bony canal and the tympanic membrane. (Item 71) The procedure described in item 70, further comprising removing bone using at least one of a diamond drill and an otological drill. (Item 72) Creating an opening in the stapes footplate is the procedure described in item 61, which includes creating an opening in the stapes footplate using a laser. (Item 73) The lasers mentioned above include otological lasers, as described in item 62. (Item 74) The procedure according to item 61, further comprising applying at least one of anesthesia and adrenaline to the patient's external auditory canal before deploying the posterior tympanic membrane valve. (Item 75) The procedure according to item 61, further comprising pre-treating the ear by applying at least one disinfectant to the ear. (Item 76) The treatment according to item 75, wherein the at least one disinfectant comprises at least one of povidone-iodine, iodopovidone, betadine, vocadine, and piodin. (Item 77) The treatment described in item 68, wherein the aforementioned at least one skin treatment comprises at least one of sodium hyaluronate and hyaluronic acid. (Item 78) A method for delivering a therapeutic fluid to a portion of the inner ear (for example, using one of the devices described in items 1-37 or 83, or one of the systems described in items 38-60), Creating an opening in the stapes footplate, The process involves piercing a circular window with a needle positioned at the distal end of a fluid delivery device, Positioning the fluid delivery device at a desired insertion depth within the circular window, This includes delivering the therapeutic fluid to the inner ear using the fluid delivery device, The method wherein the therapeutic solution comprises at least one viral gene therapy. (Item 79) A method for delivering a therapeutic fluid to a portion of the inner ear (for example, using one of the devices described in items 1-37 or 83, or one of the systems described in items 38-60), Creating an opening in the stapes footplate, The process involves piercing a circular window with a needle positioned at the distal end of a fluid delivery device, Positioning the fluid delivery device at a desired insertion depth within the circular window, This includes delivering the therapeutic fluid to the inner ear using the fluid delivery device, The method wherein the desired insertion depth includes a depth of approximately 0.7 mm to approximately 1.0 mm. (Item 80) The method according to item 79, wherein the delivery of the therapeutic fluid to the inner ear by the fluid delivery device includes delivering the therapeutic fluid at a flow rate of approximately 20 μL / min to approximately 100 μL / min. (Item 81) The method according to item 79, wherein the delivery of the therapeutic fluid into the inner ear by the fluid delivery device includes delivering a total amount of therapeutic fluid ranging from about 0.07 mL to about 0.11 mL. (Item 82) The method according to item 79, wherein the fluid delivery device delivers the therapeutic fluid into the inner ear, the therapeutic fluid being delivered for a duration ranging from about 0.5 minutes to about 5 minutes. (Item 83) A device for delivering fluid to the ear, A handle portion including the proximal and distal ends, A retractable support body is attached to the distal end of the handle portion, A needle subassembly coupled to the distal end of the telescopic support, the needle subassembly including a curved needle, A tube connected to the proximal end of the handle portion, The device comprising the above. (Item 84) A package system for holding a delivery device, comprising a distal end and a stopper positioned at the distal end of the delivery device, Mounting surface and Includes a device nesting section for holding the delivery device, The package system, wherein the device nesting portion is mounted on the mounting surface. (Item 85) A packaging system for holding a delivery device, Mounting surface and Includes a device nesting section for holding the delivery device, The package system, wherein the device nesting portion is mounted on the mounting surface. (Item 86) The system according to item 85, comprising at least one pair of oppositely oriented slits located within the mounting surface. (Item 87) The system according to item 86, wherein the at least pair of oppositely oriented slits hold a fluid-coupled tube to the proximal end of the delivery device. (Item 88) The system according to item 85, comprising a plurality of nested notches arranged within the device nest, the nested notches holding at least one of the proximal end, distal end, or body of the delivery device. (Item 89) At least one mounting slit disposed within the mounting surface, Extending across the device nesting portion and attached to the at least one mounting slit, at least one locking portion, The system described in item 85, including the system described in item 85. (Item 90) The system described in item 85, wherein the device nesting portion is of the fiddle type. (Item 91) The system according to item 85, further comprising at least one twist tie for securing the delivery device to the device nesting portion. (Item 92) The system according to item 86, wherein the at least pair of oppositely oriented slits include a pair of curved ends at either end to prevent the at least pair of oppositely oriented slits from damaging the mounting surface. (Item 93) The aforementioned delivery device, The device body includes the distal tip and the proximal tip, A tube fluidly coupled to the proximal end, The system described in item 85, comprising: (Item 94) A packaging system for holding a delivery device used to deliver therapeutic fluid to the inner ear, Mounting surface and Includes a device nesting section for holding the delivery device, The package system, wherein the device nesting portion is mounted on the mounting surface. (Item 95) A PEEK tube fluidly coupled upstream of the delivery device, A sleeve positioned around the aforementioned PEEK tube, The system described in item 94, which further includes the system described in item 94. (Item 96) The system according to item 93, further comprising sleeves arranged concentrically around the tube to prevent the tube from twisting. (Item 97) The system according to item 96, wherein the sleeve is made of a polymer material. (Item 98) A surgical procedure to deliver a therapeutic solution to a portion of the patient's inner ear, The surgical procedure comprising injecting the therapeutic solution into the inner ear using a delivery device as described herein. (Item 99) To perform transcatheter tympanotomy, Performing a laser-assisted microstapes osteotomy, The measures described in item 98, including further measures. (Item 100) It is a surgical procedure, To perform transcatheter tympanotomy, Performing a laser-assisted microstapes osteotomy, The therapeutic solution is injected into the patient's inner ear using the delivery device described herein, Applying a occlusive agent around at least one of the round window and oval window of the patient, To lower the tympanic valve of the aforementioned patient to its anatomical position, The surgical procedure, including the aforementioned surgical procedure. (Item 101) A surgical procedure to deliver a therapeutic solution to a portion of the patient's inner ear, To perform transcatheter tympanotomy, Pre-treatment of the circular window of the aforementioned patient, Performing a laser-assisted microstapes osteotomy, In order to deliver to the inner ear, both the delivery device and the therapeutic solution are pre-treated, The treatment solution is injected into the inner ear using the delivery device, Applying a occlusive agent around at least one of the round window and oval window of the patient, To lower the tympanic valve of the aforementioned patient to its anatomical position, The surgical procedure, including the aforementioned surgical procedure. (Item 102) Performing microstapes osteotomy using the aforementioned laser involves KTP otological laser and CO 2 The procedure described in item 101, which includes the use of at least one of the otological lasers. (Item 103) The treatment described in item 99, comprising the AAV vector. (Item 104) The procedure described in item 103, which includes the Anc80AAV vector. (Item 105) The procedure described in item 103, which includes a coding region that encodes hOTOF in the AAV vector. (Item 106) The device according to item 17, wherein the stopper is seated around a stopper fixing groove located within the curved needle. (Item 107) The device according to item 2, further comprising an annular brace disposed on the contact surface between the retractable support and the handle portion. (Item 108) The handle portion further comprises at least one machined barb located at the proximal end, ]> The device according to item 6, wherein at least one machined barb interfaces with the tension relief mechanism and prevents axial movement between the handle portion and the tension relief mechanism.

Brief Description of the Drawings

[0118] [Figure 1] A perspective view of a device for delivering fluid to the inner ear, according to an aspect of an embodiment of the present disclosure, is shown.

[0119] [Figure 2] A side view of a curved needle subassembly according to an embodiment of the present disclosure is shown.

[0120] [Figure 3] A perspective view of a device for delivering fluid to the inner ear according to an embodiment of the present disclosure is shown.

[0121] [Figure 4] This shows a perspective view of a curved needle subassembly coupled to the distal end of a device, according to an embodiment of the present disclosure.

[0122] [Figure 5] This shows a device coupled to a tube according to an embodiment of the present disclosure.

[0123] [Figure 6] This document shows a device coupled to a tension relaxation mechanism according to an embodiment of the present disclosure.

[0124] [Figure 7] A perspective view of a retractable hypotube needle support, needle, and stopper according to an embodiment of the present disclosure is shown.

[0125] [Figure 8] A side view of a needle according to an embodiment of the present disclosure is shown.

[0126] [Figure 9] A perspective view of a retractable hypotube needle support according to an embodiment of the present disclosure is shown.

[0127] [Figure 10] A perspective view of a tension relaxation mechanism according to an embodiment of the present disclosure is shown.

[0128] [Figure 11] A perspective view of a tube (or hoop) according to an embodiment of the present disclosure is shown.

[0129] [Figure 12] A device for delivering fluid to the inner ear according to an embodiment of the present disclosure is shown.

[0130] [Figure 13] A perspective view of a curved needle subassembly according to an embodiment of the present disclosure is shown.

[0131] [Figure 13A] A perspective view of a curved needle subassembly according to an aspect of this embodiment is shown.

[0132] [Figure 13B] A perspective view of a curved needle subassembly according to an aspect of this embodiment is shown.

[0133] [Figure 13C] A side view of a device for delivering fluid to the inner ear according to an embodiment of the present disclosure is shown.

[0134] [Figure 13D] A side view of a device for delivering fluid to the inner ear according to an embodiment of the present disclosure is shown.

[0135] [Figure 13E] A side view of a device for delivering fluid to the inner ear according to an embodiment of the present disclosure is shown.

[0136] [Figure 13F] A side view of a device for delivering fluid to the inner ear according to an embodiment of the present disclosure is shown.

[0137] [Figure 13G] A side view of a device for delivering fluid to the inner ear according to an embodiment of the present disclosure is shown.

[0138] [Figure 13H] A side view of a device for delivering fluid to the inner ear according to an embodiment of the present disclosure is shown.

[0139] [Figure 14] This document shows a device packaged in a case coupled to a tube, according to an embodiment of the present disclosure.

[0140] [Figure 14A] This shows a device packaged in another package attached to a tube, according to an aspect of this embodiment.

[0141] [Figure 15] This shows a perspective view of a distal tip camera arranged within the system according to an aspect of this embodiment.

[0142] [Figure 16] This shows a perspective view of a distal tip camera arranged within the system according to an aspect of this embodiment.

[0143] [Figure 17] This shows a perspective view of a distal tip camera arranged within the system according to an aspect of this embodiment.

[0144] [Figure 18] This shows a perspective view of a distal tip camera arranged within the system according to an aspect of this embodiment.

[0145] [Figure 19] A side view of the distal tip camera according to an embodiment of this model is shown.

[0146] [Figure 20] A side view of the distal tip camera according to an embodiment of this model is shown.

[0147] [Figure 21] A side view of the distal tip camera according to an embodiment of this model is shown.

[0148] [Figure 22] A side view of the distal tip camera according to an embodiment of this model is shown.

[0149] [Figure 23] This is a side view of an optical fiber according to an embodiment of this product.

[0150] [Figure 23A] An embodiment of the device according to this embodiment is shown.

[0151] [Figure 23B] An embodiment of the device according to this embodiment is shown.

[0152] [Figure 23C] An embodiment of the device according to this embodiment is shown.

[0153] [Figure 23D] An embodiment of the device according to this embodiment is shown.

[0154] [Figure 23E] An embodiment of the device according to this embodiment is shown.

[0155] [Figure 23F] An embodiment of the device according to this embodiment is shown.

[0156] [Figure 23G] An embodiment of the device according to this embodiment is shown.

[0157] [Figure 23H] An embodiment of the device according to this embodiment is shown.

[0158] [Figure 24] A side view of the delivery system according to an embodiment of this model is shown.

[0159] [Figure 25] A method for delivering a therapeutic solution according to an aspect of this embodiment is shown. [Modes for carrying out the invention]

[0160] Embodiments of the present disclosure will be described in detail here, one or more examples of which are shown in the accompanying drawings. The detailed description refers to mechanisms in the drawings using numerical and / or letter designations. Similar or identical names in the drawings and description are used to refer to similar or identical parts of these embodiments.

[0161] The devices, systems, and methods described herein offer potential advantages over commercially available materials and other delivery systems in terms of both the safety and efficacy of therapeutic agents. For example, the devices and systems described are specifically designed for intracochlear administration routes. In some embodiments, design elements of the devices described may include maintaining the sterility of the injected fluid, minimizing air bubbles introduced into the inner ear, the ability to deliver small amounts precisely at a controlled rate, delivery through the external auditory canal by a surgeon, minimizing damage to the round window membrane (RWM) or inner ear (e.g., cochlear structures beyond the RWM), and minimizing leakage of the injected fluid through the RWM.

[0162] The devices, systems, and methods provided herein also describe the possibility of safely and efficiently delivering fluids to the inner ear for the treatment of diseases and disorders that would benefit from fluid delivery to the inner ear, including, but are not limited to, hearing and balance disorders, or intracranial tumors such as vestibular schwannomas. As another example, by placing a vent in the stapes base plate and injecting through the RWM, the therapeutic agent is dispersed throughout the cochlea, minimizing dilution at the site of action. The development of the devices described makes it possible to perform surgical administration procedures through the human external auditory canal. The devices described can be removed from the ear after injecting a certain amount of fluid into the perilymph of the cochlea. In the patient, the device may be advanced through the external auditory canal either under the control of a surgical microscope or together with an endoscope.

[0163] device Figure 1 shows an exemplary device 10 for delivering fluid to the inner ear. The device 10 includes a knurled handle 12 and a distal handle adhesive 14 (e.g., epoxy such as Loctite 4014) that is bonded to a retractable hypotube needle support 24. The knurled handle 12 (or handle portion) may include a curling mechanism and / or grooves to enhance grip. The knurled handle 12 (or handle portion) may have a thickness of about 5 mm to about 15 mm, or about 5 mm to about 12 mm, or about 6 mm to about 10 mm, or about 6 mm to about 9 mm, or about 7 mm to about 8 mm. The knurled handle 12 (or handle portion) may be hollow, allowing fluid to pass through the device 10 during use. The device 10 may also include a proximal handle adhesive 16 at the proximal end 18 of the notched handle 12, a needle subassembly 26 (shown in Figure 2) with a stopper 28 (shown in Figure 2) at the distal end 20 of the device 10, and a tension relief mechanism 22. The tension relief mechanism 22 may consist of Santoprene material, Pebax material, polyurethane material, silicone material, nylon material, and / or thermoplastic elastomer.

[0164] The retractable hypotube needle support 24 surrounds and supports the curved needle 38 (shown in Figure 2) that is placed inside it.

[0165] Continuing to refer to Figure 1, the stopper 28 may consist of a thermoplastic material or plastic polymer (such as a UV-curing polymer) and other suitable materials and may be used to prevent the curved needle 38 from being inserted too far into the ear canal (for example, to prevent the curved needle 38 from being inserted into the side wall or other inner ear structure). The device 10 may also include a tip section 23, which is positioned between the knurled handle 12 and a distal handle adhesive 14 that is coupled to a telescopic hypotube needle support 24. The knurled handle 12 (or handle section) may include the tip section 23 at the distal end of the handle section 12. The device 10 may also include a tube 36, which is fluid-connected to the proximal end 16 of the device 10 and acts as a fluid inlet line connecting the device to an upstream component (for example, a pump, syringe, and / or, in some embodiments, an upstream component that may be coupled to a control system and / or power supply (not shown)). In some embodiments, the curved needle 38 (shown in Figure 2) extends from the distal end 20, through the retractable hypotube needle support 24, through the tip section 23, through the knurled handle 12, and through the tension relief mechanism 22, to make a direct fluid connection to the tube 36. In other embodiments, the curved needle 38 makes a fluid connection to the hollow interior of the knurled handle (e.g., via the retractable hypotube needle support 24), and then makes a fluid connection to the tube 36 at the proximal end 16. In embodiments where the curved needle 38 does not completely penetrate the interior of the device 10, the contact area (e.g., the area between the overlapping nested hypotubes 42), tolerances, and / or seals between the interacting components must be sufficient to prevent the therapeutic fluid from leaking out of the device 10 (the device 10 operates at relatively low pressures (e.g., about 1 Pascal to about 50 Pa, or about 2 Pa to about 20 Pa, or about 3 Pa to about 10 Pa)).

[0166] Figure 2 shows a side view of a curved needle subassembly 26 according to an embodiment of the present disclosure. The curved needle subassembly 26 includes a needle 38 having a bend 32. The curved needle subassembly 26 may also include a stopper 28 coupled to the bend 32. The bend 32 includes a sloping tip 34 at the distal end 20 of the device 10 for piercing the ear membrane (e.g., RWM). The needle 38, the bend 32, and the sloping tip 34 are hollow, allowing fluid to flow through them. The angle 46 of the bend 32 (shown in Figure 4) may vary. The shape of the stopper 28 may be annular, disc-shaped, annular, dome-shaped, and / or other suitable shape. The stopper 28 may be molded in place of the bend 32. For example, the stopper 28 may be positioned concentrically around the bend 32 using adhesive or compression fitting. Examples of adhesives include UV-curing adhesives (such as Dymax 203A-CTH-FT), elastomer adhesives, thermosetting adhesives (such as epoxy or polyurethane), or emulsion adhesives (such as polyvinyl acetate). The inclined tip 34 is inserted into the ear at the desired insertion depth by the concentric fitting of the stopper 28 around the bent portion 32. The curved needle 38 may be formed from a straight needle using sequential molding and other suitable techniques.

[0167] Figure 3 shows a perspective view of an exemplary device 10 for delivering fluid to the inner ear. The length of the tube 36 (dimension 11 in Figure 3) may be approximately 1300 mm to 1600 mm, or approximately 1400 mm to 1500 mm, or approximately 1430 mm to 1450 mm. The length of the tension relief mechanism 22 (dimension 15 in Figure 3) may be approximately 25 mm to 30 mm, or approximately 20 mm to 35 mm. The length of the handle 12 (dimension 13 in Figure 3) may be approximately 155.4 mm, or approximately 150 mm to 160 mm, or approximately 140 mm to 170 mm. The retractable hypotube needle support 24 may have two or more nesting hypotubes, for example, three nesting hypotubes 42A, 42B, and 42C, or four nesting hypotubes 42A, 42B, 42C, and 42D (shown in Figure 9). The total length of the hypotubes 42A, 42B, 42C and the tip assembly 26 (dimension 17 in Figure 3) may be approximately 25 mm to 45 mm, or approximately 30 mm to 40 mm, or approximately 35 mm. Furthermore, the retractable hypotube needle support 24 may have a length of approximately 36 mm, or approximately 25 mm to 45 mm, or approximately 30 mm to 40 mm. The three nesting hypotubes 42A, 42B, and 42C may have lengths of 3.5 mm, 8.0 mm, and 19.8 mm, respectively, and each may vary by ±20%. The innermost nested hypotube (or narrowest portion) of the retractable hypotube needle support 24 may be arranged concentrically around the needle 38 (shown in Figure 7).

[0168] Figure 4 shows a perspective view of a curved needle subassembly 26 coupled to the distal end 20 of the device 10, according to an embodiment of the present disclosure. As shown in Figure 4, the curved needle subassembly 26 may include a needle 38 coupled to the bend 32. In other embodiments, the curved needle 38 may be a single needle (e.g., a straight needle that is then bent to include a desired angle 46). The needle 38 may be a 33 gauge needle, or may include gauges of about 32–about 34 or about 31–35. With finer gauges, care must be taken to ensure that the tube 36 does not twist or get damaged. To securely and accurately implant the needle 38 in the inner ear, the needle 38 may be attached to the handle 12. As shown in Figure 4, the curved needle subassembly 26 may also include a stopper 28 positioned around the bend 32. Figure 4 also shows that the bend 32 may include a slanted tip 34 for piercing the ear membrane (e.g., RWM). The stopper 28 may have a height 48 of approximately 0.5 mm, or approximately 0.4 mm to approximately 0.6 mm, or approximately 0.3 mm to approximately 0.7 mm. The bent portion 32 may have a length 52 of approximately 1.45 mm, or approximately 1.35 mm to approximately 1.55 mm, or approximately 1.2 mm to approximately 1.7 mm. In other embodiments, the bent portion 32 may have a length greater than 2.0 mm, resulting in a distance between the distal end of the stopper 28 and the distal end of the inclined tip 34 of approximately 0.5 mm to approximately 1.7 mm, or 0.6 mm to approximately 1.5 mm, or approximately 0.7 mm to approximately 1.3 mm, or approximately 0.8 mm to approximately 1.2 mm. Figure 4 shows that the stopper 28 may have geometric shapes that are annular, disc-shaped, and / or dome-shaped. Those skilled in the art will understand that other geometric shapes may be used.

[0169] Delivering fluid to the cochlea to access the RWM in non-human primates (NHPs) differs from approaches used in human patients. For example, device 10 (shown in Figure 1) can be advanced through the external auditory canal of a human patient by an approach that is not feasible even for larger NHPs (such as baboons), either under the control of a surgical microscope or in conjunction with an endoscope.

[0170] In NHP, the approach to access the RWM is even more similar to the approach typically used in cochlear implant surgery for patients, and consequently, the angle 46 targeting the RWM is slightly different. For example, for use in human patients, the angle 46 shown in Figure 4 may be about 55 degrees. Alternatively, the angle 46 shown in Figure 4 may be about 30 degrees in NHP. In other embodiments, the angle 46 may be about 1 to about 70 degrees. In other embodiments, the angle 46 may be about 5 to about 70 degrees. In other embodiments, the angle 46 may be about 20 to about 70 degrees. In other embodiments, the angle 46 may be about 20 to about 60 degrees. In other embodiments, the angle 46 may be about 20 to about 50 degrees. In other embodiments, the angle 46 may be about 20 to about 40 degrees. In other embodiments, the angle 46 may be about 30 to about 70 degrees. In other embodiments, the angle 46 may be about 40 to about 60 degrees. In other embodiments, the angle 46 may be about 55 degrees. In some embodiments, the angle 46 is adjustable over an angular range during use of the device 10.

[0171] Figure 5 shows an exemplary device 10 with a protective tube casing (or sleeve) 56 around the tube 36 (shown in Figure 6) to protect it from twisting or otherwise damage. As shown in Figure 5, the device 10 may be housed within a protective device casing 54. The device casing 54 may be used to facilitate storage or handling of the device 10 before use for fluid delivery. The tube casing 56 may include one or more cylindrical pieces 58 coupled to the tube casing 56 to increase durability and reduce twisting and deformation of the tube casing 56 (and thus the tube 36). The cylindrical pieces 58 may also help maintain the helical configuration of the tube casing 56 (and thus the tube 36) during transport. In some embodiments, the tube casing (or sleeve) 56 may be made of polyetheretherketone (PEEK). In some embodiments, the tube casing 56 may be made of a thermoplastic material.

[0172] Figure 6 shows an exemplary device 10 coupled to the tension relief mechanism 22. The needle 38 (shown in Figure 1) can be attached to a fixed length of the tube 36 via or through the handle 12 (shown in Figure 1) and the retractable hypotube needle support 24 (shown in Figure 1), and the tube 36 can be attached to the syringe 60 (shown in Figure 15) used to hold the device 10.

[0173] Figure 7 shows a perspective view of the expandable hypotube needle support 24, needle 38, and stopper 28 of the device 10 according to an embodiment of the present disclosure. In some embodiments, the needle 38 may be concentrically arranged inside the narrowest portion of the expandable hypotube needle support 24.

[0174] Figure 8 shows a side view of a needle 38 according to an embodiment of the present disclosure. The needle 38 may include a bent portion 32. The bent portion 32 may include a slanted tip 34 for piercing the ear membrane (e.g., RWM). The needle 38 may be a 33 gauge needle. Other gauges may also be used, such as gauges of about 32 to about 34, or about 31 to about 35. With finer gauges, care must be taken not to damage the needle 38. The needle 38 may be made of stainless steel (e.g., 304 stainless steel). The needle 38 may also be made of any material having similar material properties (strength or other mechanical properties, etc.) to stainless steel. For example, the needle 38 may be made of titanium. The needle 38 may have a bend length of approximately 1.45 mm, or approximately 1.2 mm to approximately 1.7 mm (as shown in Figure 4), and an angle of approximately 55 degrees, or approximately 40 degrees to approximately 70 degrees (as shown in Figure 4), or approximately 20 degrees to approximately 70 degrees, with other partial ranges in between including approximately 25 degrees to approximately 45 degrees.

[0175] Figure 9 shows a perspective view of a retractable hypotube needle support 24 according to an embodiment of the present disclosure. In some embodiments, the retractable hypotube needle support 24 may include two or more nesting hypotubes, for example, four nesting hypotubes 42A, 42B, 42C, and 42D (see also Figure 3, which shows an embodiment having three nesting hypotubes 42A, 42B, and 42C). The needle 38 may be the narrowest part of the retractable hypotube needle support 24. In other embodiments, the needle 38 is located within the narrowest part 42D of the retractable hypotube needle support 24. The retractable hypotube needle support 24 may be made of stainless steel (e.g., 304 stainless steel). The retractable hypotube needle support 24 may also be made of any material having similar material properties (strength or other mechanical properties, etc.) to stainless steel. For example, the retractable hypotube needle support 24 may be made of titanium. The nesting hypotubes 42A, 42B, 42C, and 42D may include gauges of 14XH, 20TW, 23TW, and 27TW, respectively. Thus, the nesting hypotubes 42A, 42B, 42C, and 42D may include outer diameters of 0.083 inches, 0.0355 inches, 0.025 inches, and 0.014 inches, respectively, and inner diameters of 0.039 inches, 0.0255 inches, 0.017 inches, and 0.009 inches, respectively. In other embodiments, the nesting hypotubes 42A, 42B, 42C, and 42D may include outer diameters ranging from about 0.2 inches to about 0.01 inches and inner diameters ranging from 0.08 inches to 0.004 inches. Similarly, the nesting hypotubes 42A, 42B, 42C, and 42D may include wall thicknesses ranging from approximately 0.022 inches to approximately 0.003 inches, or from approximately 0.05 inches to approximately 0.001 inches.

[0176] Continuing to refer to Figure 9, the needle 38 may include gauges of approximately 32 to 34 or 31 to 35, with corresponding outer diameters of approximately 0.01 to 0.005 inches, thereby allowing the needle 38 to have an outer diameter that matches the innermost nesting hypotubes 42C and / or 42D, depending on the number of hypotubes. Each of the nesting hypotubes 42A, 42B, 42C, and 42D may also include a smooth edge between itself and one or more of the adjacent hypotubes to reduce the possibility of snagging on certain anatomical components in the external auditory canal of a human patient, for example. Each of the nesting hypotubes 42A, 42B, 42C, and 42D may also include a lip extending radially outward at its proximal end and a lip extending radially inward at its distal end, thereby preventing interference with adjacent nesting hypotubes and preventing any of the nesting hypotubes 42A, 42B, 42C, and 42D from detaching from the device 10. In other embodiments, instead of being expandable, the needle support 24 may include a single monolithic conical member whose radius gradually tapers (for example, tapering from the radius of the outermost hypotube 42A to the radius of the innermost hypotube 42D) instead of the multiple nesting hypotubes 42A, 42B, 42C, and 42D. The expandable hypotube needle support 24 may include nesting hypotubes 42B, 42C, and 42D that completely penetrate each of the adjacent wider hypotubes (as shown in Figure 9, such that the hypotube 42B extends to the distal end of the hypotube 42A).

[0177] Figure 10 shows a perspective view of a tension-relieving mechanism 22 according to an embodiment of the present disclosure. The tension-relieving mechanism 22 may include layered extruded materials 58A and 58B. The layered extruded materials 58A and 58B may include layered Pebax extruded materials. The layered extruded materials 58A and 58B can prevent twisting and / or deformation of the PEEK tube 36 (shown in Figures 5-6) at the proximal end 18 of the notched handle 12 (shown in Figure 1).

[0178] Figure 11 shows a perspective view of a tube 36 according to an embodiment of the present disclosure. The tube 36 may be made of PEEK. The tube 36 may also be made of other materials such as thermoplastic resin. The tube 36 may have an inner diameter of about 0.007 inches, or about 0.005 inches to 0.01 inches. The tube 36 may have an outer diameter of about 1 / 32 inch, or about 0.02 inches to about 0.05 inches. The tube 36 may have a length of about 60 inches, or about 30 inches to about 100 inches. In embodiments of the device 10 in which the curved needle 38 completely penetrates the knurled handle 12 and is directly fluidized to the tube 36, the proximal end of the curved needle 38 may be joined to the tube 36 by compression fitting, adhesive, ring clamp, and other suitable connections (for example, the curved needle 38 is inserted into the tube 36).

[0179] Figure 12 shows an exemplary device 10 for delivering fluid to the inner ear, which includes a retractable hypotube needle support 24 and a curved needle 38 at the distal end 20 of the device 10. As shown in Figure 12, the device 10 may include an alternative embodiment of a tension-relieving mechanism 22 that can add flexibility to the contact surface between the tube 36 and the proximal end 18 of the device. The embodiment of the tension-relieving mechanism 22 in Figure 12 can also reduce twisting or deformation of the tube 36. The tension-relieving mechanism 22 can also provide durability when the tube casing 56 (shown in Figure 5) interfaces with the proximal end 18 of the handle 12.

[0180] Figure 13 shows a perspective view of a curved needle subassembly 26 according to an embodiment of the present disclosure. The needle subassembly 26, located at the distal end 20 of the device 10, may include a beveled tip 34. A stopper 28 may be positioned around the needle 38 so that the proximal end 33 of the stopper is adjacent to the bend 32 of the needle 38. The stopper 28 may include a stopper tip section 29 whose radius gradually increases from the proximal end 33 to the distal end 35 of the stopper. The stopper may also include one or more chamfers (e.g., a chamfer 31 at the distal end 35 of the stopper).

[0181] Figure 13A shows a perspective view of the curved needle subassembly 26 including the structure of an alternative stopper 70 according to an embodiment of the present disclosure. The alternative stopper 70 in Figure 13A may be rounder and more disc-shaped or donut-shaped compared to the stopper 28 in Figure 13. For example, the alternative stopper 70 may include a maximum outer diameter that is approximately equal to its maximum length, or about 0.75 to about 1.5 times its maximum length. In contrast, the stopper 28 shown in Figure 13 may include a maximum diameter that is about 2 times its maximum length, or about 1.5 to about 2.5 times its maximum length. The alternative stopper 70 may also include a flexible portion 72 that is rounded or curved (i.e., convex) toward the distal end of the curved needle subassembly 26. The alternative stopper 70 may also include a rigid portion 74 located adjacent to the flexible portion 72. The rigid portion 74 may include an outer diameter smaller than the outer diameter of the flexible portion 72.

[0182] Figure 13B shows a perspective view of the curved needle subassembly 26 including the structure of an alternative stopper 71 according to an embodiment of the present disclosure. The alternative stopper 71 in Figure 13B includes a tapered section 77 that gradually tapers from the needle to the outer circumference 79 of the stopper. The alternative stopper 71 may also include a lip section 75 that extends slightly toward the distal tip of the needle 34. The alternative stopper 71 may also include a thinner aspect ratio (for example, compared to the stoppers in Figures 13 and 13A), resulting in the maximum diameter of the stopper 71 (e.g., the diameter measured at the outer circumference 79) being about 10 times larger than the minimum thickness of the stopper 71. In other embodiments, the maximum diameter of the stopper 71 may be about 7 to 12 times larger than the minimum thickness of the stopper 71, or about 5 to 15 times larger than the minimum thickness of the stopper 71.

[0183] Figure 13C shows an embodiment of the distal end 20 (including the needle tip 34) of the device 10 according to an aspect of this embodiment. In the embodiment shown in Figure 13C, the device 10 includes a stopper fixing groove 200 located within the device 10 at the distal end 20. The stopper fixing groove 200 can be used to help to fix stoppers 28, 70, 71 (shown in Figures 2, 4, 13, 13A, 13B, and 15-18) around the needle 38 at the distal end 20.

[0184] Figure 13D is an enlarged view of the stopper fixing groove 200 according to an aspect of this embodiment. The stopper fixing groove 200 may include a first inclined portion 202 (for example, adjacent to the distal end 20 of the stopper fixing groove 200), a second inclined portion 204 (for example, adjacent to the proximal end 18 of the stopper fixing groove 200), and a recess 206 (or flat portion 206) axially positioned between the first inclined portion 202 and the second inclined portion 204 (thereby forming the stopper fixing groove 200). The recess 206 has a diameter smaller than the rest of the needle 38. Each of the first inclined portion 202 and the second inclined portion 204 may transition linearly from the outer circumference of the needle 38 to the recess 206 and / or become rounded (thereby forming one or more fillets).

[0185] Figure 13E is an enlarged view of the transition between the device handle 12 and the expandable hypotube 24 according to an embodiment of this design. In the embodiment shown in Figure 13E, the device may include a lip joint 210 (or brace, e.g., an annular brace) that reinforces the transition between the device handle 12 and the expandable hypotube 24. Thus, the lip joint 210 (or brace) may be positioned at the contact surface between the handle portion 12 and the expandable hypotube 24 (or support). The lip joint 210 may include an outer diameter larger than the outer diameter of the handle portion 12, so that a portion of the lip joint 210 is positioned around the handle portion 12. The lip joint 210 may also include an inner diameter that fits snugly around the outer diameter of the thickest member of the multiple expandable hypotube 24.

[0186] Figure 13F shows an embodiment of the device 10 according to an aspect of this embodiment. In the embodiment shown in Figure 13F, the device 10 includes a machined barb 212 integrated into the proximal end 18 of the device handle 12. The machined barb 212 may be used in conjunction with the tension relief mechanism 22 (shown in Figures 1, 3, 12, and 13H) to prevent the tension relief mechanism 22 from axially dislodging from the device handle 12.

[0187] Figure 13G is an enlarged view of a machined barb 212 according to an embodiment of this product. The machined barb 212 may include a first inclined portion 214 (for example, located at the proximal end 18 of the device handle 12), a second inclined portion 216, and a plateau portion positioned between the first inclined portion 214 and the second inclined portion 216.

[0188] Figure 13H is an enlarged view of the tension relief mechanism 22 according to an aspect of this embodiment. (The device shown in Figure 13H is shown in the opposite orientation to the device in Figures 13F and 13G.) The PEEK tube 36 can be bonded (e.g., via epoxy 220) or otherwise coupled to the device handle 12. The tension relief mechanism 22 may be positioned around the PEEK tube 36, and the PEEK tube 36 itself may be positioned around the needle 38 to prevent twisting (and / or other damage to the needle 38). Furthermore, machined barbs 212 help prevent the tension relief mechanism 22 from detaching or separating from the device handle 212. In some embodiments, the tension relief mechanism may consist of molded Santoprene, among other suitable materials. In some embodiments, the PEEK tube 36 may be divided around the needle 38 in order to position the PEEK tube 36 around the needle 38. A heat-shrinkable sleeve (not shown) may be placed over the joint between the PEEK tube 36 and the needle 38. The joint may then be exposed to heat. After exposure to heat, the joint may be reflowed or reshaped to leave a smooth final shape.

[0189] Package System Figure 14 shows a package 55 containing a device 10 encased in a device casing 54 and coupled to a tube casing 56. For example, package 55 may provide a sterilization device 10 for delivering fluid to an RWM through the ear canal. The device 10 may be a single-use disposable product. In this embodiment, the device is properly disposed of (e.g., in a biohazard sharps container). In some embodiments, package 55, tube casing 56, device casing 54, device 10, and their components are all constructed from materials robust enough to withstand gamma ray sterilization (e.g., gamma irradiation using cobalt 60 radiation to kill microorganisms and pathogens). In some embodiments, package 55, tube casing 56, device casing 54, device 10, and their components are all constructed from materials with sufficient temperature resistance to withstand steam sterilization.

[0190] Figure 14A shows a top perspective view of the device 10 nested in an alternative package 100 (or package system 100) according to an aspect of this embodiment. The package (or package system) 100 enables the safe and sterile transport and / or shipment of the device 10. The package 100 may include a mounting surface 80 and a device nest 90 positioned on the mounting surface 80. The mounting surface 80 may consist of cardboard, rigid cardboard, or polymer material. The mounting surface 80 may also consist of cardboard or rigid cardboard with a polymer coating. The device nest 90 may consist of a material similar to that of the mounting surface 80. The device nest 90 may protrude from the plane of the mounting surface 80. The mounting surface 80 may include several pairs of oppositely oriented slits 114. Slits may be cut into the mounting surface 80 to help hold the PEEK tube 36 in place, thereby preventing the PEEK tube 36 (and the metal tube within it) from twisting, torsion, breaking, and / or otherwise being damaged. Each slit in each pair of opposite-facing slits 114 may include a pair of curved ends 118 at either end to prevent the mounting surface 80 from tearing and / or cracking due to external forces acting on the opposite-facing slits 114. The opposite-facing slits 114 prevent excessive and / or insufficient twisting of the PEEK tube 36 (and the metal tube within it). This is because, while the PEEK tube 36 is being coiled, the slits being positioned on either side of the PEEK tube 36 (i.e., radially inward and radially outward) ensures that the desired radius of the PEEK tube 36 is maintained. In the embodiment shown in Figure 14A, the mounting surface 80 includes a total of five pairs of oppositely oriented slits 114. However, in other embodiments, the mounting surface 80 may include, as necessary, a number of other pairs of oppositely oriented slits 114, including 1, 2, 3, 4, 6, 7, 8, 9, 10 and / or 11 or more.

[0191] Continuing to refer to Figure 14A, the alternative package (or package system) 100 may include at least one pair of oppositely oriented slides 116 adjacent to the Luer lock 61 to support the Luer lock 61 and prevent it from being damaged. The device nest 90 may be used to support the device 10 and may include several pairs of nesting notches 84, 86, 88, 92, 94, 96 to prevent the device 10 from moving laterally or longitudinally within the device nest 90. For example, nesting notch pair 84 is positioned to hold the tension relief mechanism 22 (shown in Figures 1 and 12), nesting notch pairs 86, 88, and 92 are positioned at the proximal end of the body of the device 10, and nesting notch pairs 94 and 96 are positioned toward the distal end of the device 10. The device nest 90 may include a first contour 114 near the middle section of the device body 10 to accommodate a semi-flexible twist tie 76 used to secure the device to the device nest 90. The device nest 90 may also include a first twist tie hole 78 and a second twist tie hole 82, which allow the twist tie 76 to extend beneath the device nest 90, thereby extending around the bottom of a portion of the device nest 90 to hold the device nest 90 and the device 10 together in close contact. The device nest 90 may also include a tip hole 104 at its distal end to protect the tip and curved needle subassembly of the device 10. Thus, the tip of the device 10 can rest within the tip hole 104, minimizing the risk of damage from the tip coming into contact with any structure.

[0192] Continuing to refer to Figure 14A, the device nest 90 may include a second contour 102 at its distal end to accommodate the tip and tip hole 104 of the device 10. The device nest 90 extends gradually away from the device centerline (i.e., the center of the pair of nesting notches 84, 86, 88, 92, 94, and 96) at each of the first contour 114 and the second contour 102, resulting in the device nest 90 forming a fiddle or violin shape, which includes a neck 120 longitudinally positioned between the first contour 114 and the second contour 102. The wall of the device nest 90 protruding from the plane of the mounting surface 80 may become gradually so, for example, as shown by the tip section 98 which gradually transitions downward from the raised projection (or wall) of the neck 120 to the plane of the mounting surface 80. The package (or package system) 100 in the embodiment of Figure 14A may also include a tube casing (or sleeve) 56 (shown in Figures 5 and 14). The tube casing (or sleeve) 56 may be arranged concentrically around the PEEK tube 36 to help protect the PEEK tube 36 and prevent it from twisting, bending, and / or otherwise being damaged. The tube casing (or sleeve) 56 may be installed around the PEEK tube 36 (for example, before shipping or transporting the device 10 and / or system 100) and may be removed by detaching the Luer lock 61 from the PEEK tube 36 and / or before connecting the Luer lock 61 to the PEEK tube 36. The tube casing (or sleeve) 56 may consist of any suitable material such as polymers such as PEEK, composite materials, metallic materials, and other suitable materials.

[0193] Continuing to refer to Figure 14A, the package (or package system) 100 may include one or more locking mechanisms, the locking mechanism including a first locking portion 106 near the proximal end of the device 10 and the device nest portion 90, and a second locking portion 108 near the distal end of the device 10. The second locking portion 108 may extend across the neck 120 of the device nest portion 90. Each of the first locking portion 106 and the second locking portion 108 extends from one side of the mounting surface 80 across the device nest portion 90 (i.e., after the device 10 is installed in the device nest portion 90) to the mounting surface 80 on the opposite side of the device nest portion 90. The first locking portion 106 and the second locking portion 108 can be attached to the first mounting slit 110 and the second mounting slit 112, respectively, with the first mounting slit 110 located within the mounting surface 80 at the proximal end of the device insert portion 90, and the second mounting slit 112 located at the distal end of the device insert portion 90. The first locking portion 106 interfaces with and is attached to the first mounting slit 110, while the second locking portion 108 interfaces with and is attached to the second mounting slit 112. The device insert portion 90 can be bonded to the mounting surface 80 using any suitable mechanism, including epoxy, fusion, bonding, adhesive, and other suitable means. Furthermore, in some embodiments, the device insert portion 90 can be formed by 3D printing (e.g., by fused deposition modeling (FDM), stereolithography (SLA), and other modalities). In some embodiments, the package 100, the device nest 90, the mounting surface 80, and their components are all constructed from materials (e.g., polymers, thermosetting plastics, thermoplastics, composite materials, and other materials) that are sufficiently temperature resistant to withstand steam sterilization, gamma irradiation (using cobalt-60 radiation to kill microorganisms and pathogens), and other sterilization methods.

[0194] system The systems of this disclosure may include at least one distal tip camera (DTC) for visualizing and / or monitoring the delivery of fluid to a target (e.g., the outer ear, middle ear, and / or inner ear). In some embodiments, the distal tip camera may be operably coupled to device 10, while in other embodiments, the distal tip camera may be installed as part of device 10 (i.e., an all-in-one device). The distal tip camera may include at least one of a charge-coupled device (CCD) and a complementary metal-oxide-semiconductor (CMOS). The distal tip camera may include at least one image sensor (e.g., a lens) which receives, carries, and / or converts signals (e.g., analog or digital signals) from the target (e.g., the outer ear, middle ear, and / or inner ear). In some embodiments, the distal tip camera may further include at least one processor (e.g., a video processor or a distal tip camera processor) for processing images and / or controlling the distal tip camera, while in other embodiments, the processor may be located separately from the distal tip camera. The tip camera and / or image sensor may include a rectangular parallelepiped shape, a chip shape, a flat cubic shape, a cylindrical shape, and combinations thereof.

[0195] Figure 15 shows a perspective view of a distal tip camera 1004 positioned on a stopper 28 within the system 1000 according to an embodiment of this model. The stopper 28 may be attached to the outer surface 1020 of the bent portion 32 of the needle 38. The distal tip camera 1004 may be operably coupled to the wire 1002. In some embodiments, the distal tip camera 1004 may be positioned on the front surface 1006 of the stopper 28. In some embodiments, the distal tip camera 1004 may be embedded in the front surface 1006 of the stopper 28. The front surface 1006 may face a target (e.g., the outer ear, middle ear, and / or inner ear). In some embodiments, the distal tip camera 1004 may be positioned on the front surface 1008 of the stopper 28 (not shown).

[0196] Figure 16 shows a perspective view of a distal tip camera 1004 positioned in a cavity 1010 within a stopper 28 in a system 1000, according to an aspect of this embodiment. The stopper 28 may be attached to the outer surface 1020 of the bent portion 32 of the needle 38. The distal tip camera 1004 may be operably coupled to the wire 1002. The cavity 1010 may be created by cutting a portion (e.g., up to 30%) of the stopper 28. In some embodiments, the cavity 1010 may be near or to the outer surface 1020 of the device 10.

[0197] Figure 17 shows a perspective view of a distal tip camera 1004 positioned behind the stopper 28 in the system 1000 according to an embodiment of this model. The stopper 28 may be attached to the outer surface 1020 of the bent portion 32 of the needle 38. The distal tip camera 1004 may be operably coupled to the wire 1002. In some embodiments, the distal tip camera 1004 may be positioned on the back surface 1012 of the stopper 28 (as shown in Figure 17), while in some embodiments, the distal tip camera 1004 may be positioned behind the back surface 1012 of the stopper 28 (as shown in Figures 23D and 23F).

[0198] Figure 18 shows a perspective view of a distal tip camera 1004 arranged within the system 1000 according to an aspect of this embodiment. The stopper 28 may be attached to the outer surface 1020 of the bent portion 32 of the needle 38. The distal tip camera 1004 may be operably coupled to the wire 1002. The distal tip camera 1004 may include a light source 1022 (e.g., an LED light source) or may be operably coupled to the light source 1022. In some embodiments, the distal tip camera 1004 and / or the light source 1022 may be positioned on top of the stopper 28. In some embodiments, the distal tip camera 1004 and / or the light source 1022 may be positioned on or embedded in the stopper 28 (not shown). In some embodiments, the distal tip camera 1004 and / or the light source 1022 may be behind the stopper 28 (not shown).

[0199] Referring to Figures 15–18, the distal tip camera 1004 may be operably coupled to the outer surface 1020 of the bent portion 32 of the needle 38. In one or more embodiments, the stopper 28 may be transparent and / or may include a transparent portion 1014 for viewing through the stopper 28 in order for the distal tip camera 1004 to monitor and / or visualize a target (e.g., the outer ear, middle ear, and / or inner ear). The transparent portion 1014 may include at least a transparent material (e.g., plastic, thermoplastic resin, polymer, and / or other suitable material). In some embodiments, the transparent portion 1014 may be part of the cavity 1010. In one or more embodiments, about 30% (or about 20%–40%) of the stopper 28 may be removed so that the tip camera 1004 may be integrated into and / or included in the needle subassembly 26 (Figures 2 and 13).

[0200] Continuing to refer to Figures 15-18, the distal tip camera 1004 may be operably coupled to at least one of the power sources via the wire 1002 to supply power to the tip camera 1004 and / or to communicate with the tip camera 1004. In some embodiments, a section of the wire 1002 may be operably attached to the outer surface 1020 of the needle 38. In some embodiments, a section of the wire 1002 may be operably embedded inside a part of the device 10. For example, in one or more embodiments, the wire 1002 may be located outside the curved needle 38 and the telescopic hypotube needle support 24, while also extending at least partially inside the handle 12 of the device 10. In some embodiments, the wire 1002 may have a diameter of up to 10 mm. In some embodiments, the wire 1002 may have a diameter of up to 5 mm. In some embodiments, the wire 1002 may have a diameter of up to 3 mm. In some embodiments, the wire 1002 may have a diameter of up to 1 mm. In some embodiments, the wire 1002 may have a maximum diameter of 0.8 mm. In some embodiments, the wire 1002 may have a maximum diameter of 0.6 mm. In some embodiments, the wire 1002 may have a maximum diameter of 0.4 mm. In some embodiments, the wire 1002 may have a maximum diameter of 0.2 mm. In some embodiments, the wire 1002 may have a maximum diameter of 0.1 mm. In some embodiments, the wire 1002 may have a maximum diameter of 0.05 mm.

[0201] Figure 19 shows a side view of the distal tip camera 1004A according to an embodiment of this model. The distal tip camera 1004A may include an image sensor 1102A, which receives, transmits, and / or converts signals (e.g., analog or digital signals) from a target (e.g., the outer ear, middle ear, and / or inner ear) into an image. The image sensor 1102A may have a rectangular parallelepiped shape.

[0202] Figure 20 shows a side view of the distal tip camera 1004B according to an embodiment of this model. The distal tip camera 1004B may include a distal tip camera module 1104A including an image sensor 1102A, a processor (e.g., a video processor, or a processor embedded in the distal tip camera 1004), and / or other elements (e.g., drivers and / or software packages) for the tip camera 1004B to access and manipulate / / or process images (e.g., images from the image sensor 1102A). In some embodiments, the distal tip camera module 1104A may include package dimensions of up to 0.7 mm × 0.7 mm with a height z of up to 1.2 mm. In some embodiments, the distal tip camera module 1104A may include package dimensions of up to 1.1 mm × 1.1 mm with a height z of up to 2.4 mm. In some embodiments, the distal tip camera module 1104A may include package dimensions of up to 1.5 mm × 1.5 mm with a height z of up to 3 mm. In some embodiments, the distal tip camera module 1104A may include package dimensions of up to 2 mm × 2 mm with a height z of up to 5 mm.

[0203] Referring to Figures 19 to 20, the image sensor 1102A can be up to 10mm×10mm, 5mm×5mm, 2mm×2mm, 1.8mm×1.8mm, 1.6mm×1.6mm, 1.4mm×1.4mm, 1.2mm×1.2mm, 1mm×1mm, 0.8mm×0.8mm, 0.6mm×0.6mm, 0.4mm×0.4mm, 0.2mm×0.2mm, 0.1mm×0.1mm, or 0.05mm×0.05mm, with a maximum height of 100, 20, 10, 5, 3, 2, 1, 0.8, 0.6, 0.4, 0.2, or 0.1mm.

[0204] Continuing to refer to Figures 19 to 20, the image sensor 1102A may include an image array capable of capturing video at resolutions of at least 10×10, 50×50, 100×100, 200×200, 400×400, 500×500, or 1000×1000 pixels at a frame rate of at least 5, 10, 20, 30, 50, 100, 100, 100, 200×200, 400×400, 500×500, or 1000×1000 pixels.

[0205] Continuing to refer to Figures 19 to 20, the image sensor 1102A may include image areas of up to 10mm×10mm, 5mm×5mm, 2mm×2mm, 1.8mm×1.8mm, 1.6mm×1.6mm, 1.4mm×1.4mm, 1.2mm×1.2mm, 1mm×1mm, 0.8mm×0.8mm, 0.6mm×0.6mm, 0.4mm×0.4mm, 0.2mm×0.2mm, 0.1mm×0.1mm, or 0.05mm×0.05mm. The image sensor 1102A may include low light sensitivities of up to 10, 100, 500, 800, 1000, 1200, 1500, 2000, 3000, or 10,000mV / lux-sec.

[0206] Continuing to refer to Figures 19 to 20, the image sensor 1102A may include optical formats up to 10, 5, 2, 1.8, 1.6, 1.4, 1.2, 1, 0.8, 0.6, 0.4, 0.2, 0.1, or 0.05 mm and pixel sizes up to 10, 8, 6, 4, 3, 2.5, 2.2, 2, 1.8, 1.6, 1.4, 1.2, or 1 μm.

[0207] Figure 21 shows a side view of the distal tip camera 1004C according to an embodiment of this model. The distal tip camera 1004C may include an image sensor 1102C, which receives, transmits, and / or converts signals (e.g., analog or digital signals) from a target (e.g., the outer ear, middle ear, and / or inner ear) into an image. The image sensor 1102C in Figure 21 may include a chip or cylinder shape.

[0208] Figure 22 shows a side view of the distal tip camera 1004D according to an embodiment of this model. The distal tip camera 1004D may include a distal tip camera module 1104C including an image sensor 1102C, a processor (e.g., a video processor or an integrated distal tip camera processor), and / or other elements (e.g., drivers and / or software packages) for the tip camera 1004D to access an image (e.g., an image from the image sensor 1102C) and manipulate and / or process that image.

[0209] Referring to Figures 21 and 22, the image sensor 1102C may include an outer diameter of up to 10 mm, 5 mm, 2 mm, 1.8 mm, 1.6 mm, 1.4 mm, 1.2 mm, 1 mm, 0.8 mm, 0.6 mm, 0.4 mm, 0.2 mm, 0.1 mm, or 0.05 mm, and a length of up to 100, 20, 10, 5, 3, 2, 1, 0.8, 0.6, 0.4, 0.2, or 0.1 mm.

[0210] Continuing to refer to Figures 21 and 22, the image sensor 1102C may include an image array capable of capturing video at resolutions of at least 10×10, 50×50, 100×100, 200×200, 400×400, 500×500, or 1000×1000 pixels at a frame rate of at least 5, 10, 20, 30, 50, 100, 100, 100, 200×200, 400×400, 500×500, or 1000×1000 pixels.

[0211] Continuing to refer to Figures 21 and 22, the image sensor 1102A may include image areas of up to 10mm×10mm, 5mm×5mm, 2mm×2mm, 1.8mm×1.8mm, 1.6mm×1.6mm, 1.4mm×1.4mm, 1.2mm×1.2mm, 1mm×1mm, 0.8mm×0.8mm, 0.6mm×0.6mm, 0.5mm×0.5mm, 0.4mm×0.4mm, 0.2mm×0.2mm, 0.1mm×0.1mm, or 0.05mm×0.05mm. The image sensor 1102A may include low light sensitivities of up to 10, 100, 500, 800, 1000, 1200, 1500, 2000, 3000, or 10,000mV / lux-sec.

[0212] Referring to Figures 19 to 22, the image sensors 1102A and C can be assembled using integrated circuit packages (e.g., chip-scale packages (CSPs)) having areas of up to 0.1 mm × 0.1 mm, 0.3 mm × 0.3 mm, 0.6 mm × 0.6 mm, 0.9 mm × 0.9 mm, 1.2 mm × 1.2 mm, or 2 mm × 2 mm.

[0213] Continuing to refer to Figures 19 to 22, the distal end cameras 1004A to D may include a shutter (e.g., a rolling shutter) (not shown). The distal end cameras 1004A to D may operate at temperatures from -20°C to 70°C. The distal end cameras 1004A to D may include a field of view of at least 90, 100, 120, 130, or 150 degrees. In some embodiments, the distal end cameras 1004A to D may include at least one internal light source, while in some embodiments, the distal end cameras 1004A to D may be externally coupled to at least one light source (e.g., an LED light source 1022).

[0214] Figure 23 is a side view of an optical fiber 1302 according to an embodiment of this invention. In this disclosure, the optical fiber 1302 may be used as a light source, an image sensor 1004E, or both. The optical fiber 1302 may include at least a single optical fiber. In some embodiments, the optical fiber 1302 may have a diameter of up to 5 mm and a length of up to 10 m. In some embodiments, the optical fiber 1302 may have a diameter of up to 1 mm and a length of up to 10 m. In some embodiments, the optical fiber 1302 may have a diameter of up to 0.5 mm and a length of up to 10 m. In some embodiments, the optical fiber 1302 may have a diameter of up to 0.4 mm and a length of up to 10 m. In some embodiments, the optical fiber 1302 may have a diameter of up to 0.3 mm and a length of up to 1 m. In some embodiments, the optical fiber 1302 may have a diameter of up to 0.2 mm and a length of up to 1 m. In some embodiments, the optical fiber 1302 may have a diameter of up to 0.1 mm and a length of up to 0.1 m.

[0215] Referring to Figures 19 to 23, the distal end cameras 1004A to E and / or optical fibers 1302 may include or interface with a processor (e.g., a video processor) (not shown) with dimensions of up to 0.01 mm × 0.01 mm × 0.01 mm, 0.1 mm × 0.1 mm × 0.1 mm, 0.2 mm × 0.1 mm × 0.2 mm, 0.3 mm × 0.1 mm × 0.4 mm, 0.3 mm × 0.3 mm × 0.4 mm, 0.4 mm × 0.4 mm × 0.4 mm, or 1 mm × 1 mm × 1 mm. In some embodiments, the image sensors 1102A, C may not be larger or longer than the distal end camera modules 1104A, C.

[0216] Continuing to refer to Figures 15 to 23, the distal tip camera 1004 may include at least one of the distal tip cameras 1004A to D, an optical fiber 1302, and / or a combination thereof. The image sensor 1102 may include at least one of the image sensors 1102A and C, an optical fiber 1302, and / or a combination thereof.

[0217] Continuing to refer to Figures 15 to 23, in one or more embodiments, the distal tip camera 1004 may, for convenience, include features such as biocompatibility, lead-free, autofocus, disposable, reusable, low noise, low power consumption, low heat, and / or low noise. The distal tip camera 1004 may produce color images, grayscale images, and / or combinations thereof.

[0218] Continuing to refer to Figures 15 to 23, in some embodiments, the distal tip camera 1004 may have a maximum working distance of 100 mm. In some embodiments, the distal tip camera 1004 may have a maximum working distance of 50 mm. In some embodiments, the distal tip camera 1004 may have a maximum working distance of 20 mm. In some embodiments, the distal tip camera 1004 may have a maximum working distance of 10 mm. In some embodiments, the distal tip camera 1004 may have a maximum working distance of 5 mm.

[0219] Figures 23A, 23B, and 23C show a device 10 including a distal tip camera 1004 integrated into a stopper 28. Figure 23A shows the device 10 with a tip circled in A, and shows the area of ​​detail in Figures 23B and 23C. Figure 23B shows a perspective view of the tip, while Figure 23C shows a side view of the tip. In embodiments of Figures 23A, 23B, and 23C, the device 10 may include a lens or sensor 1102 and a camera unit (e.g., distal tip camera 1004) integrated into the stopper 28. In some embodiments, the stopper 28 may be molded around the distal tip camera 1004. The distal tip camera 1004 may also be attached to the stopper 28 by adhesive, epoxy, and / or other suitable mechanism. Wires 1002 provide power and communication links to the distal tip camera 1004. In some embodiments, the wire 102 may be sized to extend or route between two of the telescopic hypotubes (for example, between two of the members 42A, 42B, 42C, or 42D in Figure 9).

[0220] Figures 23D, 23E, and 23F show a device 10 including a distal tip camera 1004 axially separated from the stopper 28 (e.g., behind the stopper 28). In the embodiments of Figures 23D, 23E, and 23F, the device 10 may include a distal tip camera 1004 and a lens 1102 mounted on one of the telescopic hypotubes (e.g., members 42A, 42B, 42C, or 42D in Figure 9), which may be positioned and / or tilted to capture a representative view at the tip of the needle. The distal tip camera 1004 may be attached to the hypotube by adhesive, epoxy, welding, and / or other suitable mechanism. Figure 23E includes a tilted configuration 1103 including a distal tip camera 1004 and a lens or sensor 1102.

[0221] Figures 23G and 23H show a device 10, which includes a distal tip camera 1004, a lens 1102, and a wire 1002, mounted along one of the expandable hypotubes (e.g., members 42A, 42B, 42C, or 42D in Figure 9). The distal tip camera 1004 may be attached to the hypotube by adhesive, epoxy, welding, and / or other suitable mechanism. In the embodiments of Figures 23G and 23H (and Figures 23A to 23F), the device 10 may include a camera module casing 1106 that encloses the distal tip camera 1004, the lens 1102, and the wire 1002 from the outside.

[0222] Referring to Figures 15 to 23 (including Figures 23A to 23H), in some embodiments, the device (including the camera) includes an effective total diameter of less than approximately 10 mm, or approximately 1 mm to approximately 10 mm, or approximately 1 mm to approximately 8 mm, or approximately 1 mm to approximately 5 mm, or approximately 1 mm to approximately 4 mm, or approximately 2 mm to approximately 4 mm, or approximately 1 mm to approximately 3 mm, or approximately 1.5 mm to approximately 3 mm, or approximately 1 mm to approximately 2.5 mm, and / or less than approximately 3 mm.

[0223] Figure 24 shows a system 2400 including device 10 according to an embodiment of the present disclosure. System 2400 may also include a distal tip camera 1004, wire 1002, light source 1022, and / or monitor 2402 as described herein. Monitor 2402 may be operably coupled to the distal tip camera 1004. In some embodiments, system 2400 may further include one or more syringes 60 for injecting fluid, one or more pumps 2408 fluid-connected to syringes or tubes 36 (shown in Figures 3 to 5), power supply 2410, sterilizer, sharp object container (e.g., biohazard sharp object container), drill 2404 (e.g., otological drill, and / or diamond drill), and / or laser 2406 (e.g., KTP or CO2 otological laser) (not shown). In some embodiments, system 2400 may include a microscope, endoscope, and / or fiberscope (not shown) (for example, if system 2400 does not have a distal tip camera 1004). Syringe 60 may include a "Luer-Lok® syringe" and may include capacities from about 1 mL to about 100 mL, which include various capacities and partial ranges between them, including about 2 mL, about 2.5 mL, about 5 mL, about 10 mL, about 20 mL, about 30 mL, about 50 mL, and / or about 60 mL. Syringe 60 may include graduations from about 0.002 mL to about 2.0 mL, or about 0.005 mL to about 1.0 mL, or about 0.01 mL to about 0.5 mL, or about 0.05 mL to about 0.2 mL, or about 0.1 mL. Syringe 60 preferably and / or optionally, meets ISO 13485 and other applicable safety and quality standards.

[0224] Continuing to refer to Figure 24, pump 2408 is capable of generating desired fluid and pressure conditions in accordance with this disclosure and can be integrated with syringe 60. Pump 2408 may include the Medfusion® 3500 syringe pump and / or Harvard Instrument 70-2000, and / or other designs, configurations, and arrangements (including pumps from other OEMs) in accordance with this disclosure, as long as pump 2408 is capable of generating desired fluid and pressure conditions. Pump 2408 can be adapted to a variety of syringe capacities, ranging from approximately 1 mL to approximately 100 mL. Pump 2408 can also accommodate a variety of flow rates, including approximately 1 mL / hour to 50 mL / hour, or approximately 2 mL / hour to 40 mL / hour, or approximately 3 mL / hour to 25 mL / hour, or approximately 4 mL / hour to 20 mL / hour, or approximately 5 mL / hour to 15 mL / hour, or approximately 8 mL / hour to 12 mL / hour, or approximately 0.5 mL / hour to 15 mL / hour, or approximately 1 mL / hour to 12 mL / hour, or approximately 2 mL / hour to 10 mL / hour, or approximately 2.5 mL / hour to 8 mL / hour, or approximately 3 mL / hour to 7 mL / hour, or approximately 4 mL / hour to 6 mL / hour. Pump 2408 may have an operating range of relative pressure or gauge pressure of approximately 0 psi to approximately 50 psi and can accommodate back pressures in the range of approximately -300 mmHg to approximately +900 mmHg while simultaneously delivering the desired flow rate to the device.

[0225] Continuing to refer to Figure 24, device 10 is coupled to syringe 60 via a Luer lock 61 (e.g., a "Luer-Lok® syringe" which can be integrated with syringe 60 and / or pump 2408) to minimize the introduction of air during fluid delivery to the ear and ensure proper connection with tube 36 (e.g., Figures 1, 3, 6, and / or 12). The Luer lock 61 (or Luer fitting) may include a custom bushing insert used to assist in degassing the system (i.e., used to help remove air from the system). The custom bushing may be molded silicone (or other suitable material) and may be inserted inside the Luer lock 61 (or fitting). The custom bushing may be substantially cylindrical in shape with a central borehole (or lumen) in which the end of the PEEK tube 36 may be located. The central borehole (or lumen) may include a conical inlet. The amount of air inside the Luer lock 61 (or fitting) is minimized by helping the custom bushing occupy the "dead space" within the Luer lock 61 (or fitting). The Luer lock 61 may include a Luer lock and / or Luer slip connector, and may include a slip tip. Furthermore, the Luer lock 61 may include a male thread coupled to a syringe 60 interface with a female thread coupled to a needle 38, as well as other suitable leak-free connector and / or coupling configurations. The syringe 60 may be used to inject therapeutic fluids, such as small molecules or biologics, therapeutic agents which may be for antibody or viral gene therapy. The syringe 60 may be packaged separately from other device components to accommodate device pretreatment. The syringe 60 may be sterilized. Device pretreatment may be performed outside the operating room (e.g., in a pharmacy). Device pretreatment may be performed inside the operating room. Device pretreatment may be performed using a sterile field and / or sterilization equipment. By including a distal tip camera 1004 in the device 10, surgeons can see every corner, eliminating the need to remove obstacles such as protruding bones.Furthermore, using a delivery device 10 (or microcatheter) with an implanted distal end camera 1004, surgeons can perform surgery with a single tool to pierce a circular window, deliver therapeutic fluid, and visualize the outer, middle, and / or inner ear.

[0226] method Figure 25 illustrates a method 2500 that may be used to place a device 10 (or microcatheter) and deliver a fluid, such as a therapeutic fluid, to the inner ear, according to an aspect of this embodiment. In some embodiments, the present disclosure describes a delivery approach that utilizes widely accepted minimally invasive surgical techniques for accessing the middle and / or inner ear through the external auditory canal. The procedure involves opening one of the physical barriers between the middle and inner ear at the oval window, and then using the delivery device 10 (or microcatheter) to deliver a therapeutic fluid (e.g., including one or more biological agents such as viral gene therapy for treating hearing impairment) through the oval window membrane at a controlled flow rate and in a fixed amount. Figure 25 illustrates a surgical procedure that is generally applicable to humans. However, similar methodologies and procedures are also applicable to mice, rodents, and non-human primates, as will be described in the following paragraphs.

[0227] The delivery device 10 may be placed in a sterile field in the operating room, with the end of the tube 36 removed from the sterile field and connected to a syringe 60 loaded with the therapeutic fluid and mounted on a pump. After properly priming the system 2400 to remove air, the needle 38 may pass through the middle ear in a visualized state (surgical microscope, endoscope, and / or distal tip camera 1004). The RWM may be punctured using the needle 38 (or microneedle). The needle 38 may be inserted until the stopper 28 contacts the RWM. The device 10 may then be held in place, during which the therapeutic fluid is delivered to the inner ear at a controlled flow rate. Once delivery is complete, the device 10 may be removed. The device 10 may be configured as a single-use disposable product. In other embodiments, the device 10 may be configured as a reusable, sterile product with, for example, a replaceable and / or sterile needle subassembly 26. The single-use device 10 may be properly disposed of after administration is complete (e.g., in a biohazard sharps container).

[0228] Referring to Figure 25, a surgical procedure or method 2500 for delivering a therapeutic solution to a patient's inner ear may, in step 2502, include marking the ear to be treated with an indelible marker. In step 2504, method 2500 may include inducing general anesthesia in the patient. In step 2506, method 2500 may include positioning the patient supine (i.e., lying on their back) by turning the patient's head to the side so that the marked ear faces upward. In step 2508, method 2500 may include pre-treating the ear by applying an antiseptic (such as povidone-iodine, iodopovidone, betadine, vocadine, piodin, and / or other suitable antiseptics) and draping the ear and surrounding area (e.g., covering the area immediately surrounding the ear and / or otherwise creating a sterile barrier around the ear while allowing access to the ear to minimize the risk of infection and / or contamination). In step 2510, method 2500 includes applying lidocaine, epinephrine, and / or other anesthetics and adrenaline in the four-quadrant block to the external auditory canal. A surgical microscope, endoscope, and / or distal tip camera 1004 may be used to precisely apply the lidocaine and epinephrine. The application of lidocaine and epinephrine may include, but is not limited to, a composition of approximately 1% lidocaine and epinephrine diluted at 1:8,000. In some embodiments, the endoscopic surgeon may use high or low concentrations of lidocaine or epinephrine, depending on the amount of composition and the desired total dose of lidocaine or epinephrine per injection. In some embodiments, the amount of composition is less than 1 mL per injection.

[0229] Continuing to refer to Figure 25, steps 2512, 2514, and 2516 describe steps for pre-treating system 2400. The system pre-treating steps (2512, 2514, and 2516) may be performed simultaneously with, before, and / or after, the patient pre-treating steps (i.e., steps 2502, 2504, 2506, 2508, and 2510). In step 2512, method 2500 may include sterilizing device 10, for example, through a sterile field (or, for example, by gamma irradiation or steam sterilization before packaging the device). In step 2514, method 2500 may include connecting tube 36 to the proximal end 16 of device 10. In step 2516, method 2500 may include priming and purging system 2400 to ensure that air bubbles are removed from all lines and that fluid suction is established in the pump. System 2400 can be primed and purged using therapeutic fluid as a purging fluid. In one embodiment, a first amount of therapeutic fluid (e.g., about 8 μL to about 24 μL, or about 12 μL to about 20 μL, or about 16 μL) is pushed through device 10 until droplets emerge from the distal end 20 of the device. Next, a second amount of therapeutic fluid (e.g., about 3 μL to about 7 μL, or about 5 μL) is pushed through device 10 to ensure that the device is thoroughly purged. In step 2518, once both the system and the patient have been pre-treated, method 2500 may include deploying the posterior tympanic membrane flap so that device 10 can reach the oval and round windows of the middle ear. In step 2520, method 2500 may include removing a finite amount of bone at the junction of the bone canal and tympanic membrane using a microcurette or drill. In step 2522, method 2500 may include forming a hole in (or opening a window in) the stapes floor plate located opposite the cochlea as a round window, thereby allowing adequate ventilation during solution delivery to the inner ear. The hole in the stapes floor plate may be formed using an otological laser (e.g., a KTP or CO2 otological laser).In step 2524, method 2500 may include removing any protruding bone (e.g., pseudomembrane or projection of a protruding bone) as necessary to expose the round window. The protruding bone may be removed using a 1 mm diamond drill. In step 2526, method 2500 may include activating the distal tip camera 1004 (which may be embedded in device 10) to assist in the insertion of device 10 into the external auditory canal and the movement of device 10 along the external auditory canal.

[0230] Continuing to refer to Figure 25, in step 2528, method 2500 may include inserting the device 10 into the external auditory canal. In step 2528, method 2500 may include the distal end 20 of the device 10 piercing the circular window (step 2530) and passing through the circular window to a depth of approximately 1 mm or less (for example, to an insertion depth of approximately 0.7 mm to 1 mm, or approximately 0.8 mm to 0.95 mm, or approximately 0.85 mm to 1.0 mm, or approximately 0.85 mm to 0.95 mm). The stopper 28 is positioned concentrically around the bent portion 32 of the needle 38 (or microneedle) in an appropriate position to ensure the correct insertion depth of the needle 38 into the circular window. In some embodiments, the distal tip camera 1004 (or endoscope and / or surgical microscope) may be used by the surgeon (e.g., in relation to a monitor 2402 or display screen communicatively coupled to the distal tip camera 1004) to ensure that the device is inserted to a precise insertion depth (step 2532). Thus, the stopper 28 may be used primarily to ensure that the insertion depth does not exceed 1.0 mm, while the distal tip camera 1004 may be used to precisely position the device 10 before (and during) the insertion of the needle 38 (or microneedle) into the circular window. In other embodiments, the insertion depth may be greater than 1.0 mm, and may include, for example, depths of about 1.1 mm, about 1.2 mm, about 1.3 mm, about 1.4 mm, about 1.5 mm, about 1.6 mm, about 1.7 mm, and other partial ranges in between. In steps 2528, 2530, and / or 2532, method 2500 may include adjusting the angle or orientation of device 10 on the fly as needed during the procedure. Thus, even if the angle of the tip 34 of device 10 is fixed relative to the handle portion 12, the orientation of the tip 34 relative to the RWM may be adjusted on the fly based on the angle or range of angles to which the surgeon directs device 10. In step 2534, method 2500 may include flowing the therapeutic fluid through device 10 at a selected flow rate for a selected duration.

[0231] Continuing to refer to Figure 25, in some embodiments, the flow rate (or injection rate) may include rates of approximately 30 μL / min, or approximately 25 μL / min to approximately 35 μL / min, or approximately 20 μL / min to approximately 40 μL / min, or approximately 20 μL / min to approximately 70 μL / min, or approximately 20 μL / min to approximately 90 μL / min, or approximately 20 μL / min to approximately 100 μL / min. In some embodiments, the selected duration (i.e., the time the therapeutic fluid is flowing) may be approximately 3 minutes, or approximately 2.5 minutes to approximately 3.5 minutes, or approximately 2 minutes to approximately 4 minutes, or approximately 1.5 minutes to approximately 4.5 minutes, or approximately 1 minute to approximately 5 minutes. In some embodiments, the total amount of therapeutic fluid flowing into the inner ear may be approximately 0.09 mL, or approximately 0.08 mL to approximately 0.10 mL, or approximately 0.07 mL to approximately 0.11 mL. In some embodiments, the treatment duration may be less than one minute (e.g., about 25 to 59 seconds, or about 30 to 55 seconds, or about 31 to 45 seconds). In some embodiments, the total volume of the treatment fluid is equivalent to about 40% to 50% of the volume of the inner ear. In step 2536, method 2500 may include monitoring the distribution of the treatment fluid (or therapeutic agent) within the inner ear, including the base, middle, and apex of the cochlea (e.g., by a distal tip camera 1004, an endoscope, and / or a surgical microscope) to determine whether the insertion depth of the device 10 within the circular window should be adjusted (e.g., deeper or shallower). For example, in one or more embodiments, the cumulative amount can be monitored, while in other embodiments, the distribution of the treatment fluid into the inner ear can be visualized by adding a fluorescent agent to the treatment fluid, which can then be excited and / or activated by an optical fiber or a distal tip camera 1004. In step 2538, method 2500 may include removing device 10. In step 2540, method 2500 may include applying a skin treatment (e.g., Healon (sodium hyaluronate) or hyaluronic acid) to both (or either) the round window membrane and the stapes footplate to create a functional seal in both (or either) areas, allowing healing to occur over a subsequent period, for example, about 24 to 48 hours. In step 2542, method 2500 may include returning the posterior tympanic valve to its original (biological) position.In some embodiments of this disclosure, Method 2500 may include performing one or more steps in an order different from that shown in Figure 25, and additional steps not shown in Figure 25. In some embodiments, one or more steps may be omitted and / or performed simultaneously with at least one other step.

[0232] Specific definition To facilitate understanding of this disclosure, certain terms are first defined below. Further definitions of these terms and other terms are provided throughout this specification.

[0233] Any device, configuration, or method described herein as “comprising” one or more specified elements or steps is non-restrictive, meaning that the specified elements or steps are mandatory, but other elements or steps may be added to the scope of the configuration or method. To avoid redundancy, any device, configuration, or method described as “comprising” (or “comprises”) one or more specified elements or steps also describes a more limited corresponding configuration or method that “consisting essentially of” (or “consists essentially of” the same specified elements or steps), meaning that the configuration or method may include the specified mandatory elements or steps, and may also include additional elements or steps that do not substantially affect the basic and novel features. Any device, configuration, or method described herein as “comprising” or “consisting essentially of” one or more specified elements or steps is also understood to describe a more limited, closed-ended corresponding configuration or method that “consists of” (or “consists of”) the specified elements or steps, excluding any other unspecified elements or steps. In any configuration or method disclosed herein, any known or disclosed equivalent of any specified essential element or step may substitute for that element or step.

[0234] As used herein, “a” or “an” in relation to the features of a claim means “one or more” or “at least one.”

[0235] As used herein, “biocompatible” refers to a material that does not cause significant harm to living tissue when it comes into contact with it, for example, in vivo. In some embodiments, a material is “biocompatible” if it is suitable for administration to the inner ear. In some embodiments, a material is “biocompatible” if it is not toxic to cells. In certain embodiments, a material is “biocompatible” if its addition to cells in vitro results in 20% or less cell death, and / or in vivo administration of that material does not induce significant inflammation or other such adverse effects. In some embodiments, the materials used in the devices and systems described are biocompatible and are tested to meet Class II biocompatibility requirements (e.g., devices with short residence times (less than 24 hours) and indirect blood pathways).

[0236] As used herein, “disease,” “disorder,” and / or “disease” refers to any disease, disorder, and / or disorder that can be treated by accessing the inner ear. In some embodiments, the disease, disorder, and / or disorder is a hearing impairment (e.g., hearing loss). In some embodiments, the disease, disorder, and / or disorder is a balance disorder. In some embodiments, the disease, disorder, and / or disorder is a tumor, such as an inner ear tumor. In some embodiments, the disease, disorder, and / or disorder is a tumor, such as a vestibular schwannoma. Other diseases, disorders, and / or disorders include, but are not limited to, acoustic neuroma, age-related dizziness and balance disorders, autoimmune inner ear diseases, benign paroxysmal positional vertigo, bilateral vestibular hypofunction, CANVAS syndrome, and cholesteatoma.

[0237] As used herein, “therapeutic solution” refers to a therapeutic agent, or a fluid component comprising a delivery modality for delivering a therapeutic agent to the inner ear, such as a nucleic acid vector encoding the therapeutic agent. The therapeutic agent may be any modality, such as a small molecule or a biologic, which works to treat a disease or disorder such as hearing disorders, impairments, and / or tumors. In some embodiments, the therapeutic agent is for viral gene therapy. In some embodiments, the therapeutic agent is a therapeutic antibody. In some embodiments, the therapeutic agent is a therapeutic antisense oligonucleotide. In some embodiments, the therapeutic agent is a therapeutic nucleic acid (such as RNA or DNA). In some embodiments, the therapeutic agent is a therapeutic miRNA. In some embodiments, the therapeutic agent is a therapeutic shRNA. In some embodiments, the therapeutic agent is a therapeutic CRISPR / Cas system comprising a Cas protein and a guide molecule, such as guide RNA. In some embodiments, the therapeutic agent is delivered to the inner ear in the therapeutic solution. In some embodiments, the therapeutic agent is encoded by a delivery modality, such as a nucleic acid vector delivered to the inner ear in the therapeutic solution. In some embodiments, the therapeutic agent is formulated with one or more pharmaceutically acceptable carriers. In some embodiments, the active agent exists in a unit dose suitable for administration in a therapeutic regime that exhibits a statistically significant probability of achieving a predetermined therapeutic effect when administered to a suitable population. In some embodiments, the therapeutic solution may be particularly suitable for administration by injection, i.e., for example, in aqueous or non-aqueous solutions or suspensions.

[0238] As used herein, the term “pharmaceutically acceptable” may be used, for example, in relation to a carrier used to formulate the therapeutic solution disclosed herein, meaning that the carrier is compatible with the other components of the fluid component and is not harmful to its recipient.

[0239] As used herein, the term “treatment” (also “care” or “treatment”) means the administration of any therapeutic agent (also “therapy”) that partially or completely reduces, improves, eliminates, restores, alleviates, or suppresses one or more symptoms, characteristics, and / or causes of a particular disease, disorder, and / or disorder, delays their onset, reduces their severity, and / or reduces their incidence. In some embodiments, such treatment may be for a patient who does not show signs of the disease, disorder, and / or disorder in question, and / or for a patient who shows only early signs of the disease, disorder, and / or disorder. Alternatively or additionally, such treatment may be for a patient who shows signs of one or more of the diseases, disorders, and / or disorders in question. In some embodiments, treatment may be for a patient who has been diagnosed with the disease, disorder, and / or disorder in question. In some embodiments, treatment may be for a patient who is known to have one or more susceptibility factors that are statistically correlated with an increased risk of developing a given disease, disorder, and / or disorder. In some embodiments, the patient may be a human being.

[0240] As used herein, the term “substantially” refers to a qualitative condition that indicates the entire or nearly entire range or degree of the characteristics or properties of the subject matter.

[0241] Equal parts This disclosure is described in relation to its detailed description, but it should be understood that the foregoing description is intended to illustrate the claims and not to limit them. Other embodiments, advantages, and modifications are within the scope of the following claims.

[0242] This specification discloses the best mode of the invention by means of examples, and enables a person skilled in the art to practice these embodiments, including creating and using any device or system and performing any of the incorporated methods. The patentable scope of these embodiments is defined by the claims and may include other examples that a person skilled in the art can conceive. Such other examples are intended to be within the scope of the claims if they include structural elements that are not different from the language of the claims, or if they include equivalent structural elements that are only slightly different from the language of the claims.

Claims

1. A device for delivering fluid to the ear, wherein the device is A handle portion including the proximal and distal ends, A retractable support body is attached to the distal end of the handle portion, A needle subassembly coupled to the distal end of the handle portion and coupled to the distal end of the telescopic support, wherein the needle subassembly includes a curved needle, The tube connected to the proximal end of the handle portion and Equipped with, The device wherein the curved needle extends through the handle portion and is directly fluid-connected to the tube.

2. The device according to claim 1, wherein the expandable support comprises a plurality of nesting hypotubes.

3. The aforementioned curved needle is An angled tip for piercing at least one membrane, Bent part and The device according to claim 1, including the device described in claim 1.

4. The device according to claim 1, further comprising a tension-relaxing mechanism coupled to the proximal end of the handle portion, wherein the tension-relaxing mechanism prevents twisting and / or deformation of the tube.

5. The device according to claim 1, comprising a distal tip camera, wherein the distal tip camera is located within the needle subassembly.

6. The device according to claim 1, wherein the tube is coupled to the curved needle inside the hollow interior of the handle portion.

7. The device according to claim 1, wherein the bent portion has a length of 0.5 mm to 5 mm.

8. The device according to claim 3, wherein the angle of the inclined tip is 20 degrees to 70 degrees.

9. The device according to claim 1, wherein the curved needle includes a gauge in the range of 10 to 35, and the curved needle is made of stainless steel.

10. The curved needle is equipped with a stopper, The device according to claim 3, wherein the stopper is positioned within the inner ear and is shaped and sized to control the distance the inclined tip protrudes into the cochlea.

11. The device according to claim 10, wherein the stopper includes a cylindrical disc type.

12. The stopper is molded to fit the curved needle appropriately. The device according to claim 10, wherein the stopper prevents the curved needle from being inserted into at least one membrane by a desired amount.

13. The stopper is positioned at a distance of 0.2 mm to 1.2 mm from the distal end of the inclined tip. The stopper includes a diameter of 0.2 mm to 1.2 mm. The device according to claim 10, wherein the stopper includes a height of 0.2 mm to 1.0 mm.

14. The device according to claim 2, wherein each of the plurality of nested hypotubes comprises a gauge of 10 to 30, and each of the plurality of nested hypotubes comprises stainless steel.

15. The device according to claim 1, wherein the handle portion further includes a tip portion disposed at the distal end of the handle portion, the retractable support is coupled to the tip portion, and the handle portion tapers towards the distal end such that the proximal end of the retractable support is coupled to the distal end.

16. The device according to claim 1, wherein the expandable support tapers from an outer diameter of 0.2 inches or less at the proximal end to an outer diameter of 0.01 inches or more at the distal end.

17. The device according to claim 1, wherein the handle portion includes machined grooves for tactile sensation and control.

18. The device according to claim 1, wherein the tension relief mechanism includes a layered extruded material.

19. The device according to claim 6, wherein the tube is coupled to the curved needle via compression fitting.

20. The device according to claim 6, wherein the tube contains polyetheretherketone (PEEK).

21. The tube has an inner diameter of 0.003 inches to 0.01 inches. The tubes include outer diameters ranging from 1 / 64 inch to 1 / 16 inch. The device according to claim 6, wherein the tube includes a length greater than 20 inches.

22. The device according to claim 1, wherein the device is sterile and / or biocompatible.

23. The device according to claim 3, wherein the inclined tip protrudes from the bent portion of the curved needle to form an outlet for distributing fluid.

24. It is a system, The device according to claim 1, A sterile syringe fluid-coupled to the aforementioned tube, pump and A system equipped with these features.

25. The system according to claim 24, wherein the pump controls the flow rate of the fluid passing through any one of the devices at a rate of 10 μL / min to 200 μL / min.

26. The device according to claim 10, wherein the stopper is seated around a stopper fixing groove.

27. The device according to claim 1, further comprising an annular brace disposed on the contact surface between the retractable support and the handle portion.

28. The handle portion further comprises at least one machined barb located at the proximal end, The device according to claim 4, wherein the at least one machined barb interfaces with the tension relief mechanism and prevents axial movement between the handle portion and the tension relief mechanism.

Images