Devices, systems, and methods for delivering a fluid to the inner ear

Abstract

A device (10) for delivering fluid to the ear comprises: 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 bent needle (38); and a tubing (36) coupled to the proximal end of the handle portion (12). The bent needle (38) extends through the handle portion (12) and is directly fluidically connected to the tubing (36).

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to and the benefit of U.S. Provisional Patent Application Serial No. 63 / 030,519, filed on May 27, 2020; U.S. Provisional Patent Application Serial No. 63 / 126,270, filed on December 16, 2020; and U.S. Provisional Patent Application Serial No. 63 / 151,610, filed on February 19, 2021, all of which are entitled “DEVICES, SYSTEMS, AND METHODS FOR DELIVERING FLUID TO THE INNER EAR,” the disclosures of which are incorporated herein by reference in their entirety. Background Art

[0003] Delivering therapeutic agents to the inner ear presents significant challenges. The relevant organs are buried deep within the skull, encased in bone, and isolated from the circulatory system by the blood-cochlear barrier. Some organs of the inner ear, including the organ of Corti, are particularly difficult to access and fragile.

[0004] Fluid containing a therapeutic agent can be delivered to the middle ear cavity, hoping that the fluid diffuses across the round window membrane (RWM) into the inner ear. However, only a small percentage of the administered fluid and therapeutic agent actually enters the fluid space of the inner ear. Distribution throughout the inner ear typically relies on simple diffusion, which causes the delivered fluid and therapeutic agent to be highly diluted by the time they reach their target site of action in the inner ear. Summary of the Invention

[0005] Embodiments disclosed herein include devices, systems, and methods for delivering fluids to the inner ear. The devices, systems, and methods described herein include devices for administering fluids to the perilymph of the inner ear. In some embodiments, the described devices, systems, and methods offer potential advantages over available devices, systems, and methods in terms of both the safety and efficacy of fluids including therapeutic agents administered via an intracochlear route.

[0006] In some embodiments, design elements of the described devices and systems include: maintaining sterility of the injection fluid; minimizing the introduction of air bubbles into the inner ear; the ability to precisely deliver small volumes (e.g., when coupled using a standard pump) at a controlled flow rate; allowing visualization of the round window membrane (RWM) during delivery through the external auditory canal by a surgeon; minimizing damage to the RWM or inner ear structures outside the RWM; and minimizing leakage of test sample through the RWM.

[0007] In one aspect, the present disclosure provides a device for delivering fluid to an ear, the device comprising: a handle portion including a proximal end and a distal end; a needle subassembly coupled to the distal end of the handle portion and comprising a bent needle; and a tubing coupled to the proximal end of the handle portion. The bent needle extends through the handle portion and is directly fluidically connected to the tubing.

[0008] In some embodiments, the device includes a telescoping support coupled to the proximal end of the needle subassembly.

[0009] In some embodiments, the distal end of the handle is coupled to a proximal end of the telescoping support.

[0010] In some embodiments, the telescoping support comprises a plurality of nested hypotubes.

[0011] In some embodiments, the bent needle comprises: an angled tip for piercing at least one membrane; and a bent portion.

[0012] In some embodiments, the device includes a strain relief feature coupled to the proximal end of the handle portion.

[0013] In some embodiments, the device includes a camera (eg, a distal tip camera). The distal tip camera is positioned within the needle subassembly.

[0014] In some embodiments, the tube is coupled to the bending needle within the hollow interior of the handle portion.

[0015] In some embodiments, the device comprises an inner diameter of about 0.005 inches to about 0.01 inches.

[0016] In some embodiments, the bend has a length of about 0.5 mm to about 5 mm (eg, about 1 mm to about 3 mm, such as about 1.4 mm).

[0017] In some embodiments, the angle is from about 20 degrees to about 70 degrees (e.g., from about 20 degrees to about 60 degrees, e.g., from about 20 degrees to about 50 degrees, e.g., from about 20 degrees to about 40 degrees, e.g., about 30 degrees, e.g., from about 30 degrees to about 70 degrees, e.g., from about 40 degrees to about 60 degrees, e.g., about 55 degrees).

[0018] In some embodiments, the angle is about 30 degrees.

[0019] In some embodiments, the angle is about 55 degrees.

[0020] In some embodiments, the curved needle comprises a gauge in the range of about 10 to about 35, such as about 20 to about 35, such as about 30 to about 35, such as 33 gauge.

[0021] In some embodiments, the bending needle is at least partially constructed of stainless steel.

[0022] In some embodiments, the device includes an adhesive disposed on the proximal end and the distal end of the handle portion.

[0023] In some embodiments, the device includes a stopper coupled to the curved needle. The stopper is shaped and sized to be positioned within the inner ear and to control the distance that the angled tip protrudes into the cochlea.

[0024] In some embodiments, the barrier comprises a cylinder-disc shape.

[0025] In some embodiments, the stopper is molded into place on the bending pin, and the stopper prevents the bending pin from being inserted into at least one membrane more than a desired amount.

[0026] 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 distal end of the angled tip.

[0027] In some embodiments, the barrier comprises a diameter of about 0.2 mm to about 1.2 mm (eg, about 0.4 mm to about 1.0 mm, eg, about 0.6 mm to about 0.9 mm, eg, about 0.85 mm).

[0028] In some embodiments, the barrier comprises a height of about 0.2 mm to about 1.0 mm (eg, about 0.3 mm to about 0.7 mm, eg, about 0.4 mm to about 0.6 mm, eg, about 0.5 mm).

[0029] In some embodiments, each hypotube in the plurality of nested hypotubes includes a model number of about 10 to about 30 (eg, 14XH, 20TW, 23XTW, and / or 27TW).

[0030] In some embodiments, each hypotube in the plurality of nested hypotubes comprises stainless steel.

[0031] In some embodiments, the handle portion further comprises a tapered portion disposed at the distal end of the handle, the telescoping support being coupled to the tapered portion. The handle tapers downwardly to a first distal end (e.g., such that a second proximal end of the telescoping support is coupled to the first distal end).

[0032] In some embodiments, the telescoping 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.

[0033] In some embodiments, the handle portion includes machined grooves for feel and control.

[0034] In some embodiments, the handle portion is shaped and sized to facilitate placement into the inner ear.

[0035] In some embodiments, the strain relief feature comprises a layered extrusion (eg, a layered Pebax extrusion).

[0036] In some embodiments, the strain relief feature prevents kinking and / or deformation of the tubing.

[0037] In some embodiments, the tubing is coupled to the bending needle via a compression fit.

[0038] In some embodiments, the tubing comprises polyetheretherketone (PEEK).

[0039] In some embodiments, the tubing comprises an inner diameter of about 0.003 inches to about 0.01 inches (eg, about 0.007 inches).

[0040] In some embodiments, the tubing comprises an outer diameter of about 1 / 64 inch to about 1 / 16 inch (eg, about 1 / 32 inch).

[0041] In some embodiments, the tubing comprises a length greater than 20 inches, such as greater than 30 inches, such as greater than 40 inches, such as greater than 50 inches, such as greater than 60 inches, such as about 60 inches.

[0042] In some embodiments, the device is sterile and / or biocompatible.

[0043] In some embodiments, the angled tip protrudes from the bent portion of the bent needle to form an outlet for dispensing fluid.

[0044] In another aspect, the present disclosure provides a system comprising the device and a sterile syringe fluidly coupled to the tubing.

[0045] In some embodiments, the system includes a pump.

[0046] In some embodiments, the pump controls the flow rate of fluid through any of the devices (e.g., controlled to a rate of about 10 μL / min to about 60 μL / min, such as about 15 μL / min to about 55 μL / min, such as about 20 μL / min to about 50 μL / min, such as about 25 μL / min to about 45 μL / min, such as about 25 μL / min to about 40 μL / min, such as about 20 μL / min to about 35 μL / min, such as about 30 μL / min) (e.g., controlled to a rate of about 10 μL / min to about 200 μL / min, such as about 15 μL / min to about 55 μL / min, such as about 20 μL / min to about 50 μL / min, such as about 25 μL / min to about 45 μL / min, such as about 25 μL / min to about 40 μL / min, such as about 20 μL / min to about 35 μL / min, such as about 30 μL / min). L / min, for example, about 20 μL / min to about 180 μL / min, for example, about 30 μL / min to about 180 μL / min, for example, about 40 μL / min to about 150 μL / min, for example, about 50 μL / min to about 150 μL / min, for example, about 60 μL / min to about 140 μL / min, for example, about 70 μL / min to about 130 μL / min, for example, about 80 μL / min to about 120 μL / min, for example, about 90 μL / min to about 110 μL / min, for example, about 100 μL / min).

[0047] In some embodiments, the stopper is positioned around a stopper anchoring slot disposed within the bending needle.

[0048] In some embodiments, the device includes an annular band disposed at an interface between the telescoping support and the handle portion.

[0049] In some embodiments, the device includes at least one machined barb disposed at the proximal end of the handle portion.

[0050] In some embodiments, the machined barbs interface with the strain relief feature and prevent axial movement between the handle portion and the strain relief feature.

[0051] In another aspect, the present disclosure provides a delivery system comprising: a delivery device including a distal end; a blocker disposed at the distal end of the delivery device; a distal tip camera disposed at the distal end of the delivery device, the distal tip camera including an image sensor; and a monitor operatively coupled to the distal tip camera. The monitor displays information received from the distal tip camera.

[0052] In some embodiments, the barrier is transparent.

[0053] In some embodiments, the barrier includes a transparent portion for the distal tip camera to see through the barrier.

[0054] In some embodiments, the distal tip camera is disposed above a front surface of the blocker, and the front surface of the blocker faces a target.

[0055] In some embodiments, the target is a portion of the ear.

[0056] In some embodiments, the distal tip camera is embedded (eg, integrated) within the blocker.

[0057] In some embodiments, the distal tip camera is positioned behind the blocker.

[0058] In some embodiments, the delivery system includes a guide wire operatively coupled between the distal tip camera and the monitor.

[0059] In some embodiments, the distal tip camera includes an autofocus feature.

[0060] In some embodiments, the distal tip camera comprises at least one of a cubic shape, a slice shape, a cylindrical shape, and combinations thereof.

[0061] In some embodiments, the image sensor includes a field of view of about 90° to about 150°.

[0062] In some embodiments, the image sensor comprises a cubic shape having dimensions of up to 10 mm x 10 mm and a height of up to 100 mm, and / or a cylindrical shape comprising an outer diameter of up to 10 mm and a length of up to 100 mm.

[0063] In some embodiments, the image sensor includes an image array capable of capturing video at a resolution of at least 10x10 pixels at a frame rate of at least 5 frames per second (fps).

[0064] In some embodiments, the image sensor includes an image area of at most 10 mm x 10 mm.

[0065] In some embodiments, the image sensor comprises an optical format up to 10 mm and a pixel size up to 10 μm.

[0066] In some embodiments, the delivery system includes a processor operatively coupled to the image sensor.

[0067] In some embodiments, the delivery system includes a driver package and / or a software package.

[0068] In some embodiments, the delivery system includes at least one light source.

[0069] In some embodiments, the delivery system comprises an optical fiber.

[0070] On the other hand, the present disclosure provides a distal tip camera system comprising: an image sensor disposed at a distal end of a needle including a blocker; a guide wire operatively connected to the image sensor; a processor operatively connected to the image sensor; and a monitor operatively connected to the processor to display information captured by the image sensor and processed by the processor.

[0071] In another aspect, the present disclosure provides a surgical procedure for delivering a therapeutic fluid to a portion of the inner ear (e.g., using any of the devices disclosed herein), the surgical procedure comprising: opening a posterior tympanic canal flap; creating an opening in the stapes baseplate; puncturing the 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 flowing the therapeutic fluid through the fluid delivery device to the inner ear.

[0072] In some embodiments, the procedure includes: activating a distal tip camera, endoscope, and / or surgical microscope prior to puncturing the round window; and monitoring the flow rate of the therapeutic fluid and / or the distribution of the therapeutic fluid in the inner ear via the distal tip camera, the endoscope, and / or the surgical microscope prior to puncturing the round window.

[0073] In some embodiments, the procedure includes activating a distal tip camera prior to puncturing the round window. The distal tip camera is communicatively coupled to at least one monitor viewable by a surgeon during the procedure.

[0074] In some embodiments, elevating the posterior tympanic canal flap includes cutting the posterior tympanic canal using a micro-curette and / or a drill.

[0075] In some embodiments, the procedure includes: preparing the ear and covering the ear with a drape before opening the posterior tympanic canal flap; positioning the patient before preparing and covering the ear with a drape; inducing anesthesia before positioning the patient; and marking the ear before inducing anesthesia.

[0076] In some embodiments, the procedure includes: connecting tubing between the fluid delivery device and an upstream pump before retracting the posterior tympanic membrane ear canal flap; sterilizing the fluid delivery device before retracting the posterior tympanic membrane ear canal flap; and priming the system before retracting the posterior tympanic membrane ear canal flap.

[0077] In some embodiments, the therapeutic fluid includes at least one viral gene therapy.

[0078] In some embodiments, the procedure includes: removing the fluid delivery device from the inner ear after flowing the therapeutic fluid through the fluid delivery device; and applying at least one skin treatment to the round window membrane and / or the stapes baseplate after removing the fluid delivery device.

[0079] In some embodiments, the procedure includes returning the posterior tympanic canal flap to its original position after applying at least one skin treatment.

[0080] In some embodiments, the surgery includes removing bone from the junction of the bony canal and the tympanic membrane after unfolding the posterior tympanic canal flap, and / or removing bone overhanging the pseudomembrane.

[0081] In some embodiments, the procedure includes removing bone using a diamond drill bit and / or an otological drill bit.

[0082] In some embodiments, creating an opening in the stapes baseplate includes creating an opening in the stapes baseplate using a laser.

[0083] In some embodiments, the laser comprises an otological laser.

[0084] In some embodiments, the procedure includes applying at least one of an anesthetic and epinephrine to the patient's ear canal prior to retraction of the posterior tympanic canal flap.

[0085] In some embodiments, preparing the ear further comprises applying at least one antimicrobial agent to the ear.

[0086] In some embodiments, the antimicrobial agent comprises povidone iodine, iodine povidone, betadine, wokadine, and / or pyodine.

[0087] In some embodiments, the skin treatment comprises sodium hyaluronate and / or hyaluronic acid.

[0088] In another aspect, the present disclosure provides a method for delivering a therapeutic fluid to a portion of the inner ear (e.g., using any of the devices or systems disclosed herein), the method comprising: creating an opening in the stapes footplate; puncturing the 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 flowing the therapeutic fluid through the fluid delivery device to the inner ear. The therapeutic fluid comprises at least one viral gene therapy.

[0089] In another aspect, the present disclosure provides a method for delivering a therapeutic fluid to a portion of the inner ear (e.g., using any of the devices or systems disclosed herein), the method comprising: creating an opening in the stapes footplate; puncturing the 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 flowing the therapeutic fluid through the fluid delivery device to the inner ear. The desired insertion depth comprises a depth of about 0.7 mm to about 1.0 mm.

[0090] In some embodiments, flowing the therapeutic fluid through the fluid delivery device to the inner ear comprises flowing the therapeutic fluid at a flow rate of about 20 μL / min to about 100 μL / min.

[0091] In some embodiments, flowing the therapeutic fluid through the fluid delivery device to the inner ear comprises flowing a total volume of therapeutic fluid in a range of about 0.07 mL to about 0.11 mL.

[0092] In some embodiments, flowing the therapeutic fluid through the fluid delivery device to the inner ear comprises flowing the therapeutic fluid for a duration ranging from about 1 minute to about 5 minutes.

[0093] In another aspect, the present disclosure provides a device for delivering fluid to an ear, the device comprising: a handle portion comprising a proximal end and a distal end; a telescopic support coupled to the distal end of the handle portion; a needle subassembly coupled to the distal end of the telescopic support, the needle subassembly comprising a bent needle; and a tubing coupled to the proximal end of the handle portion.

[0094] In another aspect, the present disclosure provides a packaging system for holding a delivery device, the delivery device including a distal end and a stopper disposed 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.

[0095] In another aspect, the present disclosure provides a packaging system for holding a delivery device, 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.

[0096] In some embodiments, the system includes at least one pair of oppositely oriented slots disposed in the mounting surface.

[0097] In some embodiments, the pair of oppositely oriented slits retains a tube fluidly coupled to the proximal end of the delivery device.

[0098] In some embodiments, the system includes a plurality of nesting recesses disposed within the device nest, the nesting recesses retaining at least one of the proximal end, the distal end, and the body portion of the delivery device.

[0099] In some embodiments, the system includes at least one attachment slot disposed within the mounting surface and at least one locking portion extending through the device nest and attached to the attachment slot.

[0100] In some embodiments, the device nest is folk violin-shaped.

[0101] In some embodiments, the system includes at least one tie for securing the delivery device to the device nest.

[0102] 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 causing damage to the mounting surface.

[0103] In some embodiments, the delivery device includes a device body comprising a distal tip and a proximal end, and a tubing fluidly coupled to the proximal end.

[0104] In another aspect, the present disclosure provides a packaging system for holding a delivery device for delivering 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 to the mounting surface.

[0105] In some embodiments, the system includes: PEEK tubing fluidly coupled upstream of the delivery device; and a sleeve disposed around the PEEK tubing.

[0106] In some embodiments, the system includes a sleeve concentrically disposed about the tubing to prevent kinking of the tubing.

[0107] In some embodiments, the sleeve is constructed of a polymeric material.

[0108] In another aspect, the present disclosure provides a surgical procedure for delivering a therapeutic fluid to a portion of an inner ear of a patient, the surgical procedure comprising injecting the therapeutic fluid into the inner ear via a delivery device as described herein.

[0109] In some embodiments, the surgical procedure comprises: performing a myringotomy through the external auditory canal; performing a laser-assisted microstapediotomy; and injecting the therapeutic fluid into the inner ear via a delivery device as described herein.

[0110] In some embodiments, the surgical procedure includes: performing a myringotomy through the external auditory canal; performing a laser-assisted micro-stapediotomy; injecting the therapeutic fluid into the inner ear via a delivery device as described herein; applying a sealant around the patient's round window and / or oval window; and lowering the patient's tympanic membrane ear canal flap to an anatomical position.

[0111] In some embodiments, the surgical procedure includes: performing a myringotomy through the external auditory canal; preparing the patient's round window; performing a laser-assisted micro-stapediotomy; preparing both a delivery device as described herein and the therapeutic fluid for delivery to the inner ear; injecting the therapeutic fluid into the inner ear via the delivery device; applying a sealant around the patient's round window and / or oval window; and lowering the patient's tympanic membrane ear canal flap to an anatomical position.

[0112] In some embodiments, performing the laser-assisted microstapedostomy comprises using a KTP otologic laser and / or a CO2 otologic laser.

[0113] In some embodiments, the therapeutic fluid comprises an AAV vector. In some embodiments, the AAV vector is an Anc80 AAV vector. In some embodiments, the AAV vector comprises a coding region encoding hOTOF.

[0114] Throughout the specification, where devices, systems, procedures and / or methods are described as having, including or comprising particular components, or where methods are described as having, including or comprising particular steps, it is contemplated that there are additional devices, systems, procedures and / or methods of the disclosure that consist essentially of or consist of the enumerated components, and that there are methods according to the disclosure that consist essentially of or consist of the enumerated process steps.

[0115] Should be understood that, as long as method is still operable, the order of steps or the order in which certain actions are performed is not important.In addition, two or more steps or actions can be performed simultaneously.

[0116] The following description is intended to illustrate and exemplify the present disclosure only and is not intended to limit the disclosure to the particular embodiments described.

[0117] Reference to any publication herein (e.g., in the Background section) is not an admission that the publication is available as prior art with respect to any claim of the present invention. The Background section is presented for clarity and is not intended as a description of prior art with respect to any claim. BRIEF DESCRIPTION OF THE DRAWINGS

[0118] This specification sets forth a complete and enabling disclosure of the embodiments disclosed herein, including the best mode thereof, for one of ordinary skill in the art, with reference to the accompanying drawings, in which:

[0119] Figure 1 shows a perspective view of a device for delivering fluid to the inner ear according to aspects of the disclosed embodiments of the present invention;

[0120] Figure 2 shows a side view of a bending needle subassembly according to aspects of the disclosed embodiments of the present invention;

[0121] Figure 3 shows a perspective view of a device for delivering fluid to the inner ear according to aspects of the disclosed embodiments of the present invention;

[0122] Figure 4 showing a perspective view of a bent needle subassembly coupled to a distal end of a device in accordance with aspects of the disclosed embodiments of the present invention;

[0123] Figure 5 shows a device coupled to a pipe according to aspects of the disclosed embodiments of the present invention;

[0124] Figure 6 shows a device coupled to a strain relief feature according to aspects of the disclosed embodiments of the present invention;

[0125] Figure 7 showing a perspective view of a telescoping hypotube needle support, needle, and stopper in accordance with aspects of the disclosed embodiments of the present invention;

[0126] Figure 8 shows a side view of a needle according to aspects of the disclosed embodiments of the present invention;

[0127] Figure 9showing a perspective view of a telescoping hypotube needle support according to aspects of the disclosed embodiments of the present invention;

[0128] Figure 10 A perspective view illustrating strain relief features according to aspects of embodiments disclosed herein;

[0129] Figure 11 A perspective view of a pipe (or collar) is shown according to aspects of the disclosed embodiments of the present invention;

[0130] Figure 12 shows a device for delivering fluid to the inner ear according to aspects of the disclosed embodiments of the present invention;

[0131] Figure 13 showing a perspective view of a bending needle subassembly according to aspects of the disclosed embodiments of the present invention;

[0132] Figure 13A shows a perspective view of a bending needle subassembly according to aspects of an embodiment of the present invention;

[0133] Figure 13B shows a perspective view of a bending needle subassembly according to aspects of an embodiment of the present invention;

[0134] Figure 13C shows a side view of a device for delivering fluid to the inner ear according to aspects of the disclosed embodiments of the present invention;

[0135] Figure 13D shows a side view of a device for delivering fluid to the inner ear according to aspects of the disclosed embodiments of the present invention;

[0136] Figure 13E shows a side view of a device for delivering fluid to the inner ear according to aspects of the disclosed embodiments of the present invention;

[0137] Figure 13F shows a side view of a device for delivering fluid to the inner ear according to aspects of the disclosed embodiments of the present invention;

[0138] Figure 13G shows a side view of a device for delivering fluid to the inner ear according to aspects of the disclosed embodiments of the present invention;

[0139] Figure 13H shows a side view of a device for delivering fluid to the inner ear according to aspects of the disclosed embodiments of the present invention;

[0140] Figure 14 shows a packaging device in a housing coupled to a tube according to aspects of the disclosed embodiments of the present invention;

[0141] Figure 14A shows a packaging device in an alternative packaging coupled to a tube according to aspects of an embodiment of the present invention;

[0142] Figure 15 shows a perspective view of a distal tip camera disposed within a system according to aspects of an embodiment of the present invention;

[0143] Figure 16 shows a perspective view of a distal tip camera disposed within a system according to aspects of an embodiment of the present invention;

[0144] Figure 17 shows a perspective view of a distal tip camera disposed within a system according to aspects of an embodiment of the present invention;

[0145] Figure 18 shows a perspective view of a distal tip camera disposed within a system according to aspects of an embodiment of the present invention;

[0146] Figure 19 shows a side view of a distal tip camera according to aspects of an embodiment of the present invention;

[0147] Figure 20 shows a side view of a distal tip camera according to aspects of an embodiment of the present invention;

[0148] Figure 21 shows a side view of a distal tip camera according to aspects of an embodiment of the present invention;

[0149] Figure 22 shows a side view of a distal tip camera according to aspects of an embodiment of the present invention;

[0150] Figure 23 shows a side view of an optical fiber according to aspects of an embodiment of the present invention;

[0151] Figure 23A An embodiment of an apparatus according to aspects of an embodiment of the present invention is shown;

[0152] Figure 23B An embodiment of an apparatus according to aspects of an embodiment of the present invention is shown;

[0153] Figure 23C An embodiment of an apparatus according to aspects of an embodiment of the present invention is shown;

[0154] Figure 23D An embodiment of an apparatus according to aspects of an embodiment of the present invention is shown;

[0155] Figure 23EAn embodiment of an apparatus according to aspects of an embodiment of the present invention is shown;

[0156] Figure 23F An embodiment of an apparatus according to aspects of an embodiment of the present invention is shown;

[0157] Figure 23G An embodiment of an apparatus according to aspects of an embodiment of the present invention is shown;

[0158] Figure 23H An embodiment of an apparatus according to aspects of an embodiment of the present invention is shown;

[0159] Figure 24 shows a side view of a delivery system according to aspects of an embodiment of the present invention; and

[0160] Figure 25 Methods for delivering therapeutic fluids according to aspects of embodiments of the present invention are shown. DETAILED DESCRIPTION

[0161] Reference will now be made in detail to the embodiments disclosed herein, one or more examples of which are illustrated in the accompanying drawings. The detailed description uses numerical and / or letter references to refer to features in the drawings. Like or similar reference numerals in the drawings and the description have been used to refer to like or similar parts of the embodiments of the invention.

[0162] The devices, systems, and methods described herein offer potential advantages over existing materials and other delivery systems in terms of both safety and efficacy of therapeutic agents. For example, the devices and systems described are specifically designed for intracochlear administration. In some embodiments, design elements of the devices described may include: maintaining sterility of the injection fluid; minimizing the introduction of air bubbles into the inner ear; the ability to precisely deliver small volumes at a controlled rate; delivery by a surgeon through the external auditory canal; minimizing damage to the round window membrane (RWM) or the inner ear (e.g., cochlear structures outside the RWM); and minimizing leakage of the injection fluid through the RWM.

[0163] Device, system and method provided herein also describe following potential: fluid is delivered safely and effectively in the inner ear, so that treatment will benefit from the illness and obstacle of fluid delivery to the inner ear, described illness and obstacle include but are not limited to hearing and balance disorder or intracranial tumor such as vestibular schwannoma.As another example, by arranging a discharge hole in the stapes base plate and passing through RWM injection, therapeutic agent is dispersed in the whole cochlea in the mode with minimum dilution at the site of action.The development of described device allows to perform surgical application operation through the external auditory canal of mankind.After a certain amount of fluid is infused in the perilymph of the cochlea, described device can be removed from ear.In patient's body, described device can be advanced through external auditory canal under surgical microscope control or together with endoscope.

[0164] Device

[0165] Figure 1 An exemplary device 10 for delivering fluid to the inner ear is shown. The device 10 includes a knurled handle 12 and a distal handle adhesive 14 (e.g., an epoxy such as Loctite 4014) coupled to a telescoping hypotube needle support 24. The knurled handle 12 (or handle portion) may include knurled features 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 a thickness of about 5 mm to about 12 mm, or a thickness of about 6 mm to about 10 mm, or a thickness of about 6 mm to about 9 mm, or a thickness of about 7 mm to about 8 mm. The knurled handle 12 (or handle portion) may be hollow so that fluid can 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 knurled handle 12, a stopper 28 (shown in FIG. 1 ) at the distal end 20 of the device 10, and a proximal handle adhesive 16 at the proximal end 18 of the knurled handle 12. Figure 2 The needle subassembly 26 (shown in Figure 2 ) and strain relief feature 22. The strain relief feature 22 can be made of Santoprene material, Pebax material, polyurethane material, silicone material, nylon material and / or thermoplastic elastomer.

[0166] The telescopic hypotube needle support 24 surrounds and supports the bent needle 38 disposed therein (shown in FIG. Figure 2 middle).

[0167] Still refer to Figure 1, the stopper 28 can be constructed of a thermoplastic material or a plastic polymer (such as a UV-curable polymer), among other suitable materials, and can be used to prevent the bending needle 38 from being inserted too deeply into the ear canal (e.g., to prevent the bending needle 38 from being inserted into the sidewall or other inner ear structures). The device 10 can also include a tapered portion 23 disposed between the knurled handle 12 and the distal handle adhesive 14, the tapered portion being coupled to the telescopic hypotube needle support 24. The knurled handle 12 (or handle portion) can include a tapered portion 23 at the distal end of the handle portion 12. The device 10 can also include a tubing 36 that is fluidly connected to the proximal end 16 of the device 10 and serves as a fluid inlet line connecting the device to an upstream component (e.g., a pump, a syringe, and / or an upstream component that, in some embodiments, may be coupled to a control system and / or a power source (not shown)). In some embodiments, the bending needle 38 (shown in Figure 2 10 ). In some embodiments, the bending needle 38 extends from the distal end 20, through the telescoping hypotube needle support 24, through the tapered portion 23, through the knurled handle 12, and through the strain relief feature 22, and is directly fluidly connected to the tubing 36. In other embodiments, the bending needle 38 is fluidly connected to the hollow interior of the knurled handle (e.g., via the telescoping hypotube needle support 24), which in turn is fluidly connected to the tubing 36 at the proximal end 16. In embodiments where the bending needle 38 does not extend all the way through the interior of the device 10, the contact area between the abutting components (e.g., between overlapping nested hypotubes 42), tolerances, and / or sealants must be sufficient to prevent leakage of the therapeutic fluid from the device 10 (which 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)).

[0168] Figure 2 A side view of a bent needle subassembly 26 according to aspects of an embodiment disclosed herein is shown. The bent needle subassembly 26 includes a needle 38 having a bent portion 32. The bent needle subassembly 26 may also include a stopper 28 coupled to the bent portion 32. The bent portion 32 includes an angled tip 34 at the distal end 20 of the device 10 for piercing a membrane of the ear (e.g., RWM). The needle 38, the bent portion 32, and the angled tip 34 are hollow so that fluid can flow therethrough. The angle 46 of the bent portion 32 (e.g., Figure 4The geometry of the stopper 28 may be cylindrical, disc-shaped, annular, dome-shaped, and / or other suitable shapes. The stopper 28 may be molded into position on the bend 32. For example, the stopper 28 may be positioned concentrically around the bend 32 using an adhesive or a compression fit. Examples of adhesives include UV-curable adhesives (such as Dymax 203A-CTH-FT), elastomeric adhesives, thermosetting adhesives (such as epoxies or polyurethanes), or emulsion-type adhesives (such as polyvinyl acetate). The stopper 28 fits concentrically around the bend 32 so that the angled tip 34 is inserted into the ear at a desired insertion depth. The bent needle 38 may be formed from a straight needle using incremental forming and other suitable techniques.

[0169] Figure 3 A perspective view of an exemplary device 10 for delivering fluid to the inner ear is shown. The length of the tubing 36 ( Figure 3 The dimension 11) in the embodiment may be from about 1300 mm to about 1600 mm, or from about 1400 mm to about 1500 mm, or from about 1430 mm to about 1450 mm. The strain relief feature 22 may have a length ( Figure 3 15), or a length of about 20 mm to about 35 mm. The length of the handle 12 ( Figure 3 The dimension 13) may be about 155.4 mm, or about 150 mm to about 160 mm, or about 140 mm to about 170 mm. The telescoping hypotube needle support 24 may have two or more nested hypotubes, such as three nested hypotubes 42A, 42B, and 42C, or four nested hypotubes 42A, 42B, 42C, and 42D (shown in FIG. Figure 9 The total length of the hypotubes 42A, 42B, 42C and the tip assembly 26 ( Figure 3 Dimension 17) may be about 25 mm to about 45 mm, or about 30 mm to about 40 mm, or about 35 mm. Additionally, the telescoping hypotube needle support 24 may have a length of about 36 mm, or about 25 mm to about 45 mm, or about 30 mm to about 40 mm. The three nested hypotubes 42A, 42B, and 42C may each have a length of 3.5 mm, 8.0 mm, and 19.8 mm (plus or minus about 20%), respectively. The innermost nested hypotube (or narrowest portion) of the telescoping hypotube needle support 24 may be concentrically disposed around the needle 38 (e.g., Figure 7 shown).

[0170] Figure 4 A perspective view of a bent needle subassembly 26 coupled to the distal end 20 of the device 10 is shown in accordance with aspects of the disclosed embodiments of the present invention. Figure 4As shown, the bending needle subassembly 26 may include a needle 38 coupled to the bending portion 32. In other embodiments, the bending needle 38 may be a single needle (e.g., a straight needle that is then bent so that it includes the desired angle 46). The needle 38 may be a 33 gauge needle, or may include a gauge of about 32 to about 34, or about 31 to 35. With thinner gauges, care must be taken to ensure that the tubing 36 does not kink or become damaged. The needle 38 may be attached to the handle 12 to safely and accurately place the needle 38 into the inner ear. Figure 4 As shown, the bending needle subassembly 26 may further include a stopper 28 disposed about the bending portion 32 . Figure 4 The bent portion 32 is also shown to include an angled tip 34 for piercing a membrane of the ear (e.g., RWM). The stopper 28 may have a height 48 of about 0.5 mm, or about 0.4 mm to about 0.6 mm, or about 0.3 mm to about 0.7 mm. The bent portion 32 may have a length 52 of about 1.45 mm, or about 1.35 mm to about 1.55 mm, or about 1.2 mm to about 1.7 mm. In other embodiments, the bent portion 32 may have a length greater than 2.0 mm, such that the distance between the distal end of the stopper 28 and the distal end of the angled tip 34 is about 0.5 mm to about 1.7 mm, or about 0.6 mm to about 1.5 mm, or about 0.7 mm to about 1.3 mm, or about 0.8 mm to about 1.2 mm. Figure 4 It is shown that the blocker 28 can have a cylindrical, disc-shaped and / or dome-shaped geometry. One of ordinary skill will appreciate that other geometries can be used.

[0171] The delivery of fluid to the cochlea to access the RWM in non-human primates (NHPs) differs from the methods used in human patients. For example, the device 10 (e.g., Figure 1 ) can be advanced through the external auditory canal of human patients under the control of a surgical microscope or in conjunction with an endoscope, an approach that is not feasible even in larger NHPs (such as baboons).

[0172] In NHPs, the approach to accessing the RWM is more similar to that typically used for cochlear implant surgery in patients, which results in slightly different angles for targeting the RWM. Figure 4 The angle 46 shown may be about 55 degrees for use with human patients. Alternatively, as Figure 4The angle 46 shown may be about 30 degrees in NHP. In other embodiments, the angle 46 may be about 1 degree to about 70 degrees. In other embodiments, the angle 46 may be about 5 degrees to about 70 degrees. In other embodiments, the angle 46 may be about 20 degrees to about 70 degrees. In other embodiments, the angle 46 may be about 20 degrees to about 60 degrees. In other embodiments, the angle 46 may be about 20 degrees to about 50 degrees. In other embodiments, the angle 46 may be about 20 degrees to about 40 degrees. In other embodiments, the angle 46 may be about 30 degrees to about 70 degrees. In other embodiments, the angle 46 may be about 40 degrees to about 60 degrees. In other embodiments, the angle 46 may be about 55 degrees. In some embodiments, the angle 46 may be adjusted within a certain range of angles during use of the device 10.

[0173] Figure 5 It is shown that the pipe 36 (such as Figure 6 An exemplary device 10 having a protective tube housing (or sleeve) 56 around the tube (as shown) to protect the tube from kinking or other damage. Figure 5 As shown, the device 10 can be positioned in a protective device housing 54. The device housing 54 can be used to facilitate storage or handling of the device 10 prior to use in fluid delivery. The tube housing 56 can include one or more cylindrical members 58 that are coupled to the tube housing 56 to increase durability and reduce kinking and deformation of the tube housing 56 (and therefore the tubing 36). The cylindrical members 58 can also help the tube housing 56 (and therefore the tubing 36) remain in a spiral configuration during transportation. In some embodiments, the tube housing (or sleeve) 56 can be constructed of polyetheretherketone (PEEK). In some embodiments, the tube housing 56 can be constructed of a thermoplastic material.

[0174] Figure 6 An exemplary device 10 is shown coupled to a strain relief feature 22. A needle 38 (shown in FIG. Figure 1 ) can be passed through or through the handle 12 (shown in Figure 1 The telescopic hypotube needle support 24 (shown in Figure 1 ) is attached to a fixed length of tubing 36 which can be attached to a syringe 60 (shown in FIG. Figure 15 middle).

[0175] Figure 7 A perspective view of the telescoping hypotube needle support 24, needle 38, and stopper 28 of the device 10 according to aspects of the disclosed embodiments of the present invention is shown. In some embodiments, the needle 38 can be concentrically disposed within the narrowest portion of the telescoping hypotube needle support 24.

[0176] Figure 8A side view of a needle 38 according to aspects of an embodiment disclosed herein is shown. The needle 38 may include a bend 32. The bend 32 may include an angled tip 34 for piercing the membrane of the ear (e.g., RWM). The needle 38 may be a 33 gauge needle. Other gauges, such as gauges of about 32 to about 34, or about 31 to about 35, may also be used. In thinner gauges, care must be taken to ensure that the needle 38 is not damaged. 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 as stainless steel (such as strength or other mechanical properties). For example, the needle 38 may be constructed of titanium. The needle 38 may have a gauge of about 1.45 mm, or about 1.2 mm to about 1.7 mm (e.g., Figure 4 ) and the following angles: about 55 degrees, or about 40 degrees to about 70 degrees (as shown) Figure 4 ), or about 20 degrees to about 70 degrees, and other sub-ranges therebetween including about 25 degrees to about 45 degrees.

[0177] Figure 9 A perspective view of a telescoping hypotube needle support 24 is shown according to aspects of embodiments disclosed herein. In some embodiments, the telescoping hypotube needle support 24 may include two or more nested hypotubes, such as four nested hypotubes 42A, 42B, 42C, and 42D (see also FIG. Figure 3 , which shows an embodiment with three nested hypotubes 42A, 42B, and 42C). The needle 38 can be the narrowest portion of the telescopic hypotube needle support 24. In other embodiments, the needle 38 is disposed within the narrowest portion 42D of the telescopic hypotube needle support 24. The telescopic hypotube needle support 24 can be made of stainless steel (e.g., 304 stainless steel). The telescopic hypotube needle support 24 can also be made of any material having similar material properties as stainless steel, such as strength or other mechanical properties. For example, the telescopic hypotube needle support 24 can be composed of titanium. The nested hypotubes 42A, 42B, 42C, 42D can include model numbers 14XH, 20TW, 23TW, and 27TW, respectively. Thus, the nested hypotubes 42A, 42B, 42C, 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 nested hypotubes 42A, 42B, 42C, 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 nested hypotubes 42A, 42B, 42C, 42D may include wall thicknesses ranging from about 0.022 inches to about 0.003 inches, or from about 0.05 inches to about 0.001 inches.

[0178] Still refer to Figure 9 , the needle 38 may include a gauge of about 32 to about 34, or about 31 to about 35, corresponding to an outer diameter of about 0.01 inches to about 0.005 inches, thereby allowing the needle to mate with the innermost nested hypotube 42C and / or 42D (depending on the number of hypotubes). Each of the nested hypotubes 42A, 42B, 42C, 42D may also include a smooth edge between itself and one or more adjacent hypotubes, for example, to reduce the likelihood of snagging on certain anatomical components within the external auditory canal of a human patient. Each of the nested hypotubes 42A, 42B, 42C, 42D may also include a radially outwardly extending lip at the proximal end and a radially inwardly extending lip at the distal end to interfere with adjacent nested hypotubes and prevent any of the nested hypotubes 42A, 42B, 42C, 42D from being detached from the device 10. In other embodiments, instead of telescoping, the needle support 24 may include a single, unitary conical member having a gradually decreasing radius (e.g., from the radius of the outermost hypotube 42A to the radius of the innermost hypotube 42D) in place of the multiple nested hypotubes 42A, 42B, 42C, and 42D. The telescoping hypotube needle support 24 may include nested hypotubes 42B, 42C, and 42D that extend completely through each subsequent wider hypotube (e.g., in FIG. Figure 9 (as illustrated in the figure) extending through the sea wave tube 42B to the distal end of the sea wave tube 42A.

[0179] Figure 10 A perspective view of a strain relief feature 22 according to aspects of an embodiment disclosed herein is shown. The strain relief feature 22 may include layered extrusions 58A and 58B. The layered extrusions 58A and 58B may include layered Pebax extrusions. The layered extrusions 58A and 58B may prevent strain on the knurled handle 12 (e.g., Figure 1 The PEEK tubing 36 (shown as Figures 5 and 6 kinks and / or deformations).

[0180] Figure 11A perspective view of a tubing 36 according to various aspects of an embodiment disclosed herein is shown. The tubing 36 can be made of PEEK. The tubing 36 can also be made of other materials such as thermoplastics. The tubing 36 can have an inner diameter of about 0.007 inches, or about 0.005 inches to 0.01 inches. The tubing 36 can have an outer diameter of about 1 / 32 inches, or about 0.02 inches to about 0.05 inches. The tubing 36 can have a length of about 60 inches, or about 30 inches to about 100 inches. In embodiments of the device 10 in which the bending needle 38 extends all the way through the knurled handle 12 and is directly fluidly connected to the tubing 36, the proximal end of the bending needle 38 can be coupled to the tubing 36 via a compression fit, adhesive, ring clamp, and other suitable connections (e.g., by inserting the bending needle 38 into the tubing 36).

[0181] Figure 12 An exemplary device 10 for delivering fluid to the inner ear is shown, comprising a telescoping hypotube needle support 24, a curved needle 38 at the distal end 20 of the device 10. Figure 12 As shown, the device 10 may include an alternative embodiment of the strain relief feature 22 that may add flexibility to the interface between the tubing 36 and the proximal end 18 of the device. Figure 12 The embodiment of the strain relief feature 22 can also reduce kinking or deformation of the tube 36. The strain relief feature 22 can also be provided on the tube housing 56 (e.g. Figure 5 The handle 12 is provided with a proximal end 18 (shown) for durability.

[0182] Figure 13 A perspective view of a curved needle subassembly 26 according to aspects of the disclosed embodiments of the present invention is shown. The needle subassembly 26, located at the distal end 20 of the device 10, may include an angled tip 34. The blocker 28 may be disposed about the needle 38 such that the blocker proximal end 33 is adjacent to the curved portion 32 of the needle 38. The blocker 28 may include a blocker tapered portion 29 having a radius that gradually increases from the blocker proximal end 33 toward the blocker distal end 35. The blocker may also include one or more chamfers (e.g., chamfer 31 at the blocker distal end 35).

[0183] Figure 13A A perspective view of a bent needle subassembly 26 including an alternative stopper 70 design in accordance with aspects of the disclosed embodiments of the present invention is shown. Figure 13A The alternative stopper 70 may be more rounded, which is consistent with Figure 13 For example, the alternative stopper 70 may include a maximum outer diameter that is approximately equal to its maximum length, or from about 0.75 times to about 1.5 times its maximum length. Figure 13The illustrated stopper 28 may include a maximum diameter that is approximately twice the maximum length, or from about 1.5 times to about 2.5 times the maximum length. An alternative stopper 70 may also include a flexible portion 72 that is rounded or curved (i.e., convex) toward the distal end of the bending needle subassembly 26. The alternative stopper 70 may also include a rigid portion 74 located proximal to the flexible portion 72. The rigid portion 74 may have an outer diameter that is smaller than the outer diameter of the flexible portion 72.

[0184] Figure 13B A perspective view of a bent needle subassembly 26 including an alternative stopper 71 design is shown in accordance with an embodiment of the present disclosure. Figure 13B The alternative stopper 71 includes a tapered portion 77 that tapers from the needle to an outer periphery 79 of the stopper. The alternative stopper 71 may also include a lip portion 75 that extends slightly toward the distal tip 34 of the needle. The alternative stopper 71 may also include a smaller aspect ratio (e.g., Figure 13 and Figure 13A ) such that the maximum diameter of barrier 71 (e.g., as measured at outer periphery 79) is about 10 times greater than the minimum thickness of barrier 71. In other embodiments, the maximum diameter of barrier 71 may be about 7 times to about 12 times greater than the minimum thickness of barrier 71, or about 5 times to about 15 times greater than the minimum thickness of barrier 71.

[0185] Figure 13C An embodiment of the distal end 20 (including the needle tip 34) of the device 10 is shown in accordance with aspects of embodiments of the present invention. Figure 13C In the illustrated embodiment, the device 10 includes a blocker anchoring slot 200 disposed within the distal end 20 of the device 10. The blocker anchoring slot 200 can be used to facilitate positioning of the blockers 28, 70, 71 (shown in FIG. Figure 2 、 Figure 4 、 Figure 13 、 Figure 13A 、 Figure 13B and Figures 15 to 18 Center) around the needle 38 anchored at the distal end 20.

[0186] Figure 13Dis an enlarged view of a blocker anchoring slot 200 according to aspects of an embodiment of the present invention. The blocker anchoring slot 200 may include a first downwardly inclined portion 202 (e.g., adjacent to the distal end 20 of the blocker anchoring slot 200), a second downwardly inclined portion 204 (e.g., adjacent to the proximal end 18 of the blocker anchoring slot 200), and a recessed portion 206 (or flat portion 206) axially disposed between the first downwardly inclined portion 202 and the second downwardly inclined portion 204 (thereby forming the blocker anchoring slot 200). The recessed portion 206 comprises a smaller diameter than the remainder of the needle 38. Each of the first downwardly inclined portion 202 and the second downwardly inclined portion 204 may transition linearly from the outer periphery of the needle 38 to the recessed portion 206, and / or may be rounded (thereby forming one or more fillets).

[0187] Figure 13E is an enlarged view of the transition between the device handle 12 and the telescoping hypotube 24 in accordance with aspects of an embodiment of the present invention. Figure 13E In the illustrated embodiment, the device can include a lip fitting 210 (or a hoop, e.g., an annular hoop) that enhances the transition between the device handle 12 and the telescoping hypotube 24. Thus, the lip fitting 210 (or hoop) can be disposed at the interface between the handle portion 12 and the telescoping hypotube 24 (or support member). The lip fitting 210 can include an outer diameter that is larger than the outer diameter of the handle portion 12, such that a portion of the lip fitting 210 is disposed around the handle portion 12. The lip fitting 210 can also include an inner diameter that fits tightly around the outer diameter of the thickest member of the plurality of telescoping hypotubes 24.

[0188] Figure 13F An embodiment of an apparatus 10 according to aspects of an embodiment of the present invention is shown. Figure 13F In the illustrated embodiment, 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 coupled to the strain relief feature 22 (shown in FIG. Figure 1 、 Figure 3 、 Figure 12 and Figure 13H ) in order to prevent the strain relief feature 22 from axially disengaging from the device handle 12.

[0189] Figure 13G 2 is an enlarged view of a machined barb 212 according to aspects of an embodiment of the present invention. The machined barb 212 may include a first inclined portion 214 (e.g., on the proximal end 18 of the device handle 12), a second inclined portion 216, and a flat portion disposed between the first and second inclined portions 214, 216.

[0190] Figure 13His an enlarged view of the strain relief feature 22 according to aspects of an embodiment of the present invention. Figure 13H The device shown is shown in the Figure 13F and Figure 13G ) The PEEK tubing 36 can be bonded (e.g., via epoxy 220) or otherwise coupled to the device handle 12. The strain relief feature 22 can be disposed around the PEEK tubing 36, which itself can be disposed around the needle 38 to prevent kinking (and / or other damage) of the needle 38. Additionally, the machined barbs 212 help prevent the strain relief feature 22 from being dislodged or falling off the device handle 212. In some embodiments, the strain relief feature can be comprised of molded Santoprene or other suitable materials. In some embodiments, the PEEK tubing 36 can be separated around the needle 38 to allow the PEEK tubing 36 to surround the needle 38. A heat shrink sleeve (not shown) can be placed over the joint between the PEEK tubing 36 and the needle 38. The joint can then be exposed to heat. After the heat exposure, the joint can be reflow welded or reshaped so that the remaining joint has a smooth final outer profile.

[0191] Packaging system

[0192] Figure 14 Shown is a package 55 comprising a device 10, which is enclosed in a device housing 54 and is coupled to a tube housing 56. For example, the package 55 can provide a sterile device 10 for delivering fluid to the RWM through the external auditory canal. The device 10 can also be a disposable product for single use. In this embodiment, the device is appropriately discarded (e.g., discarded in a biohazard sharps container). In some embodiments, the package 55, tube housing 56, device housing 54, device 10 and its components are all made of materials that are sufficiently strong to withstand gamma sterilization (e.g., gamma irradiation using cobalt 60 radiation to kill microorganisms and bacteria). In some embodiments, the package 55, tube housing 56, device housing 54, device 10 and its components are all made of materials that are sufficiently resistant to high temperatures to withstand steam sterilization.

[0193] Figure 14AA top perspective view of a device 10 nested in an alternative package 100 (or packaging system 100) is shown according to various aspects of an embodiment of the present invention. The package (or packaging system) 100 allows for safe and sterile transport and / or shipping of the device 10. The package 100 may include a mounting surface 80 and a device nest 90 disposed on the mounting surface 80. The mounting surface 80 may be constructed of cardboard, hardened card, or a polymeric material. The mounting surface 80 may also be constructed of cardboard or hardened card with a polymeric coating. The device nest 90 may be constructed of a similar material as 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. The slits may be cut into the mounting surface 80 to help hold the PEEK tubing 36 in place, thereby preventing the PEEK tubing 36 (and the metal tubing therein) from kinking, twisting, breaking, and / or otherwise being damaged. Each slit in each pair of oppositely oriented slits 114 may include a pair of curved ends 118 at either end to prevent the slits 114 from causing rips and / or tears in the mounting surface 80 due to external forces acting on the oppositely oriented slits 114. Because the oppositely oriented slits 114 are disposed on either side (i.e., radially inside and outside) of the PEEK tubing 36 as it is coiled, the slits prevent the PEEK tubing 36 (and the metal tubing therein) from over-kinking and / or under-kinking, thereby ensuring that the desired radius of the coiled tubing 36 is maintained. Figure 14A In the embodiment shown, the mounting surface 80 includes a total of five pairs of oppositely oriented slots 114. However, in other embodiments, the mounting surface 80 may include other numbers of pairs of oppositely oriented slots 114 as desired, including 1, 2, 3, 4, 6, 7, 8, 9, 10, and / or more than 10 pairs of oppositely oriented slots.

[0194] Still refer to Figure 14A Alternatively, the package (or packaging system) 100 may include at least one pair of oppositely oriented slideways 116 adjacent the Luer lock 61 to support the Luer lock 61 and prevent damage to the Luer lock. 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 that prevent the device 10 from moving laterally or longitudinally within the device nest 90. For example, the nesting notch pair 84 is positioned to retain the strain relief feature 22 (shown in FIG. Figure 1 and Figure 12), the pairs of nesting notches 86, 88, and 92 are positioned at the proximal end of the body of the device 10, and the pairs of nesting notches 94 and 96 are positioned toward the distal end of the device 10. The device nest 90 may include a first contoured portion 114 near the midsection of the body of the device 10 to accommodate a semi-flexible strap 76 for securing the device to the device nest 90. The device nest 90 may also include a first strap hole 78 and a second strap hole 82 to allow the strap 76 to extend beneath the device nest 90, thereby extending around the bottom of a portion of the device nest 90 to secure the device nest 90 and the device 10 together. The device nest 90 may also include a tip aperture 104 at the distal end to protect the tip and the bending needle subassembly of the device 10. Thus, the tip of the device 10 may rest within the tip aperture 104, minimizing the risk of damage due to contact of the tip with any structure.

[0195] Still refer to Figure 14A , the device nest 90 may include a second contoured portion 102 at the distal end to accommodate the tip and tip aperture 104 of the device 10. The device nest 90 gradually extends away from the device centerline (i.e., the center of the nesting notch pairs 84, 86, 8, 92, 94, and 96) at each of the first contoured portion 114 and the second contoured portion 102, such that the device nest 90 forms a folk violin or fiddle shape, including a neck portion 120 disposed longitudinally between the first contoured portion 114 and the second contoured portion 102. The walls of the device nest 90 that protrude from the plane of the mounting surface 80 may gradually achieve this effect, such as shown at the tapered portion 98, which gradually transitions downward from a raised protrusion (or wall) at the neck 120 to the plane of the mounting surface 80. Figure 14A The package (or packaging system) 100 in the embodiment of the present invention may also include a tube housing (or sleeve) 56 (shown in FIG. Figure 5 and Figure 14 ). The tubing housing (or sleeve) 56 can be concentrically disposed around the PEEK tubing 36 and helps protect the PEEK tubing 36 and prevent it from kinking, bending, and / or otherwise being damaged. The tubing housing (or sleeve) 56 can be placed around the PEEK tubing 36 (e.g., prior to shipping or transporting the device 10 and / or system 100) and can be removed by disconnecting the Luer lock 61 from the PEEK tubing 36 and / or before connecting the Luer lock 61 to the PEEK tubing 36. The tubing housing (or sleeve) 56 can be constructed of any suitable material, such as a polymer (such as PEEK), a composite material, a metallic material, and other suitable materials.

[0196] Still refer to Figure 14A, the package (or packaging system) 100 may include one or more locking features including a first locking portion 106 near the proximal end of the device 10 and the device nest 90, and a second locking portion 108 near the distal end of the device 10. The second locking portion 108 may extend through a neck 120 of the device nest 90. Each of the first locking portion 106 and the second locking portion 108 extends from one side of the mounting surface 80 and through the device nest 90 (i.e., after the device 10 has been placed within the device nest 90) and extends to the mounting surface 80 on the other side of the device nest 90. The first locking portion 106 and the second locking portion 108 may be attached to a first attachment slit 110 and a second attachment slit 112, the first attachment slit 110 being provided at the proximal end of the device nest 90 within the mounting surface 80, and the second attachment slit 112 being provided at the distal end of the device nest 90. The first locking portion 106 interfaces with and is attached to the first attachment slit 110, and the second locking portion 108 interfaces with and is attached to the second attachment slit 112. The device nest 90 can be coupled to the mounting surface 80 using any suitable mechanism, including epoxy, melting, bonding, glue, and other suitable means. In addition, in some embodiments, the device nest 90 can be formed via 3D printing (e.g., via fused deposition modeling (FDM), stereolithography (SLA), and other forms). In some embodiments, the package 100, the device nest 90, the mounting surface 80, and components thereof are constructed of materials (e.g., polymers, thermosets, thermoplastics, composites, and other materials) that are sufficiently resistant to high temperatures to withstand steam sterilization, gamma irradiation (gamma irradiation using cobalt-60 radiation to kill microorganisms and bacteria), and other sterilization methods.

[0197] system

[0198] The systems of the present 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 the device 10, while in other embodiments, the distal tip camera may be mounted as part of the device 10 (i.e., an integrated 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) to receive, transmit, and / or convert 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 also include at least one processor (e.g., a video processor or a processor built into the distal tip camera) to process images and / or control the distal tip camera, while in other embodiments, the processor may be provided separately from the distal tip camera. The distal tip camera and / or image sensor may include a cubic shape, a sliced shape, a flattened cubic shape, a cylindrical shape, and combinations thereof.

[0199] Figure 15 A perspective view of a distal tip camera 1004 disposed above a stopper 28 within a system 1000 according to aspects of an embodiment of the present invention is shown. The stopper 28 can be attached to an outer surface 1020 of the bent portion 32 of the needle 38. The distal tip camera 1004 can be operatively coupled to the guide wire 1002. In some embodiments, the distal tip camera 1004 can be disposed at a front surface 1006 of the stopper 28. In some embodiments, the distal tip camera 1004 can be embedded in the front surface 1006 of the stopper 28. The front surface 1006 can face the target (e.g., the outer ear, the middle ear, and / or the inner ear). In some embodiments, the distal tip camera 1004 can be disposed at a side surface 1008 of the stopper 28 (not shown).

[0200] Figure 16 A perspective view of a distal tip camera 1004 disposed within a cavity 1010 within a blocker 28 within a system 1000 is shown, in accordance with aspects of an embodiment of the present invention. The blocker 28 can be attached to an outer surface 1020 of the bent portion 32 of the needle 38. The distal tip camera 1004 can be operatively coupled to the guide wire 1002. The cavity 1010 can be created by cutting a portion (e.g., up to 30%) of the blocker 28. In some embodiments, the cavity 1010 can be adjacent to or adjacent to the outer surface 1020 of the device 10.

[0201] Figure 17A perspective view of a distal tip camera 1004 disposed behind a stopper 28 within a system 1000 is shown, in accordance with aspects of an embodiment of the present invention. The stopper 28 can be attached to an outer surface 1020 of the bent portion 32 of the needle 38. The distal tip camera 1004 can be operatively coupled to the guide wire 1002. In some embodiments, the distal tip camera 1004 can be disposed at a rear surface 1012 of the stopper 28 (e.g., Figure 17 ), and in some embodiments, the distal tip camera 1004 may be disposed behind the rear surface 1012 of the blocker 28 (as shown). Figure 23D and Figure 23F shown).

[0202] Figure 18 A perspective view of a distal tip camera 1004 disposed within the system 1000 is shown according to aspects of an embodiment of the present invention. The blocker 28 can be attached to an outer surface 1020 of the bent portion 32 of the needle 38. The distal tip camera 1004 can be operatively coupled to the guide wire 1002. The distal tip camera 1004 can include or be operatively coupled to a light source 1022 (e.g., an LED light source). In some embodiments, the distal tip camera 1004 and / or the light source 1022 can be disposed above the blocker 28. In some embodiments, the distal tip camera 1004 and / or the light source 1022 can be disposed at or embedded in the blocker 28 (not shown). In some embodiments, the distal tip camera 1004 and / or the light source 1022 can be behind the blocker 28 (not shown).

[0203] refer to Figures 15 to 18 , the distal tip camera 1004 can be operably coupled to an outer surface 1020 of the bend portion 32 of the needle 38. In one or more embodiments, the blocker 28 can be transparent and / or include a transparent portion 1014 for the distal tip camera 1004 to see through the blocker 28 to monitor and / or visualize a target (e.g., the outer ear, middle ear, and / or inner ear). The transparent portion 1014 can comprise at least one transparent material (e.g., plastic, thermoplastic, polymer, and / or other suitable material). In some embodiments, the transparent portion 1014 can be a portion of the cavity 1010. In one or more embodiments, approximately 30% (or approximately 20% to approximately 40%) of the blocker 28 can be removed so that the distal tip camera 1004 can be integrated and / or included in the needle subassembly 26 ( Figure 2 and Figure 13 )middle.

[0204] Still refer to Figures 15 to 18The distal tip camera 1004 can be operatively coupled to at least one power source via a wire 1002 to supply power and / or communication to the distal tip camera 1004. In some embodiments, a segment of the wire 1002 can be operatively attached to an outer surface 1020 of the needle 38. In some embodiments, a segment of the wire 1002 can be operatively embedded within a portion of the device 10. For example, in one or more embodiments, the wire 1002 can be disposed outside the bending needle 38 and the telescoping hypotube needle support 24 while also extending at least partially within the handle 12 of the device 10. In some embodiments, the wire 1002 can have a diameter of up to 10 mm. In some embodiments, the wire 1002 can have a diameter of up to 5 mm. In some embodiments, the wire 1002 can have a diameter of up to 3 mm. In some embodiments, the wire 1002 can have a diameter of up to 1 mm. In some embodiments, the wire 1002 can have a diameter of up to 0.8 mm. In some embodiments, the wire 1002 may have a diameter of up to 0.6 mm. In some embodiments, the wire 1002 may have a diameter of up to 0.4 mm. In some embodiments, the wire 1002 may have a diameter of up to 0.2 mm. In some embodiments, the wire 1002 may have a diameter of up to 0.1 mm. In some embodiments, the wire 1002 may have a diameter of up to 0.05 mm.

[0205] Figure 19 A side view of a distal tip camera 1004A according to aspects of an embodiment of the present invention is shown. Distal tip camera 1004A may include an image sensor 1102A to receive, transmit, and / or convert signals (e.g., analog or digital signals) from a target (e.g., the outer ear, middle ear, and / or inner ear) into an image. Image sensor 1102A may include a cube shape.

[0206] Figure 20A side view of a distal tip camera 1004B according to various aspects of an embodiment of the present invention is shown. The distal tip camera 1004B may include a distal tip camera module 1104A, which includes an image sensor 1102A, a processor (e.g., a video processor or a processor embedded in the distal tip camera 1004), and / or other components (e.g., a driver package and / or software package) for the distal tip camera 1004B to access, operate and / or process images (e.g., images from the image sensor 1102A). In some embodiments, the distal tip camera module 1104A may include a package size of up to 0.7 mm × 0.7 mm with a z-height of up to 1.2 mm. In some embodiments, the distal tip camera module 1104A may include a package size of up to 1.1 mm × 1.1 mm with a z-height of up to 2.4 mm. In some embodiments, the distal tip camera module 1104A may include a package size of up to 1.5 mm × 1.5 mm with a z-height of up to 3 mm. In some embodiments, the distal tip camera module 1104A may include a package size of up to 2 mm x 2 mm with a z-height of up to 5 mm.

[0207] refer to Figures 19 to 20 , the image sensor 1102A can be up to 10mm x 10mm, 5mm x 5mm, 2mm x 2mm, 1.8mm x 1.8mm, 1.6mm x 1.6mm, 1.4mm x 1.4mm, 1.2mm x 1.2mm, 1mm x 1mm, 0.8mm x 0.8mm, 0.6mm x 0.6mm, 0.4mm x 0.4mm, 0.2mm x 0.2mm, 0.1mm x 0.1mm, or 0.05mm x 0.05mm, and up to 100, 20, 10, 5, 3, 2, 1, 0.8, 0.6, 0.4, 0.2, or 0.1mm in height.

[0208] Still refer to Figures 19 to 20 , image sensor 1102A may include an image array capable of capturing at least 10x10, 50x50, 100x100, 200x200, 400x400, 500x500, or 1000x1000 pixel resolution video at a frame rate of at least 5, 10, 20, 30, 50, 100, 500, or 1000 frames per second (fps).

[0209] Still refer to Figures 19 to 20Image sensor 1102A may include an image area of up to 10 mm x 10 mm, 5 mm x 5 mm, 2 mm x 2 mm, 1.8 mm x 1.8 mm, 1.6 mm x 1.6 mm, 1.4 mm x 1.4 mm, 1.2 mm x 1.2 mm, 1 mm x 1 mm, 0.8 mm x 0.8 mm, 0.6 mm x 0.6 mm, 0.4 mm x 0.4 mm, 0.2 mm x 0.2 mm, 0.1 mm x 0.1 mm, or 0.05 mm x 0.05 mm. Image sensor 1102A may include a low light sensitivity of up to 10, 100, 500, 800, 1000, 1200, 1500, 2000, 3000, or 10,000 mV / lux-sec.

[0210] Still refer to Figures 19 to 20 , image sensor 1102A can include an optical format of 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 a pixel size of up to 10, 8, 6, 4, 3, 2.5, 2.2, 2, 1.8, 1.6, 1.4, 1.2, or 1 μm.

[0211] Figure 21 A side view of a distal tip camera 1004C according to aspects of an embodiment of the present invention is shown. The distal tip camera 1004C may include an image sensor 1102C to receive, transmit, and / or convert signals (e.g., analog or digital signals) from a target (e.g., the outer ear, middle ear, and / or inner ear) into an image. Figure 21 The image sensor 1102C may include a slice or cylindrical shape.

[0212] Figure 22 A side view of a distal tip camera 1004D according to aspects of an embodiment of the present invention is shown. The distal tip camera 1004D may include a distal tip camera module 1104C that includes an image sensor 1102C, a processor (e.g., a video processor or a processor built into the distal tip camera), and / or other components (e.g., a driver package and / or software package) for the distal tip camera 1004D to access, manipulate, and / or process images (e.g., images from the image sensor 1102C).

[0213] refer to Figures 21 to 22, image sensor 1102C may include an outer diameter of up to 10mm, 5mm, 2mm, 1.8mm, 1.6mm, 1.4mm, 1.2mm, 1mm, 0.8mm, 0.6mm, 0.4mm, 0.2mm, 0.1mm or 0.05mm and a length of up to 100, 20, 10, 5, 3, 2, 1, 0.8, 0.6, 0.4, 0.2 or 0.1mm.

[0214] Still refer to Figures 21 to 22 , image sensor 1102C may include an image array capable of capturing at least 10x10, 50x50, 100x100, 200x200, 400x400, 500x500, or 1000x1000 pixel resolution video at a frame rate of at least 5, 10, 20, 30, 50, 100, 500, or 1000 frames per second (fps).

[0215] Still refer to Figures 21 to 22 Image sensor 1102A may include an image area of up to 10 mm x 10 mm, 5 mm x 5 mm, 2 mm x 2 mm, 1.8 mm x 1.8 mm, 1.6 mm x 1.6 mm, 1.4 mm x 1.4 mm, 1.2 mm x 1.2 mm, 1 mm x 1 mm, 0.8 mm x 0.8 mm, 0.6 mm x 0.6 mm, 0.5 mm x 0.5 mm, 0.4 mm x 0.4 mm, 0.2 mm x 0.2 mm, 0.1 mm x 0.1 mm, or 0.05 mm x 0.05 mm. Image sensor 1102A may include a low light sensitivity of up to 10, 100, 500, 800, 1000, 1200, 1500, 2000, 3000, or 10,000 mV / lux-sec.

[0216] refer to Figures 19 to 22 , image sensors 1102A, 1102C may be assembled using an integrated circuit package (e.g., a chip scale package (CSP)) having an area of up to 0.1 mm x 0.1 mm, 0.3 mm x 0.3 mm, 0.6 mm x 0.6 mm, 0.9 mm x 0.9 mm, 1.2 mm x 1.2 mm, or 2 mm x 2 mm.

[0217] Still refer to Figures 19 to 22, distal tip cameras 1004A to 1004D may include a shutter (e.g., a rolling shutter) (not shown). Distal tip cameras 1004A to 1004D may operate at a temperature between -20°C and 70°C. Distal tip cameras 1004A to 1004D may include a field of view of at least 90, 100, 120, 130, or 150 degrees. In some embodiments, distal tip cameras 1004A to 1004D may include at least one internal light source, while in some embodiments, distal tip cameras 1004A to 1004D may be externally coupled to at least one light source (e.g., LED light source 1022).

[0218] Figure 23 A side view of an optical fiber 1302 according to various aspects of an embodiment of the present invention is shown. In the present disclosure, optical fiber 1302 can be used as a light source, an image sensor 1004E, or both. Optical fiber 1302 can include at least a single optical fiber. In some embodiments, optical fiber 1302 can have a diameter of up to 5 mm and a length of up to 10 m. In some embodiments, optical fiber 1302 can have a diameter of up to 1 mm and a length of up to 10 m. In some embodiments, optical fiber 1302 can have a diameter of up to 0.5 mm and a length of up to 10 m. In some embodiments, optical fiber 1302 can have a diameter of up to 0.4 mm and a length of up to 10 m. In some embodiments, optical fiber 1302 can have a diameter of up to 0.3 mm and a length of up to 1 m. In some embodiments, optical fiber 1302 can have a diameter of up to 0.2 mm and a length of up to 1 m. In some embodiments, optical fiber 1014 can have a diameter of up to 0.1 mm and a length of up to 0.1 m.

[0219] refer to Figures 19 to 23 The distal tip cameras 1004A to 1004E and / or the optical fibers 1302 may include or work with a processor (e.g., a video processor) (not shown) having dimensions of up to 0.01 mm x 0.01 mm x 0.01 mm, 0.1 mm x 0.1 mm x 0.1 mm, 0.2 mm x 0.1 mm x 0.2 mm, 0.3 mm x 0.1 mm x 0.4 mm, 0.3 mm x 0.3 mm x 0.4 mm, 0.4 mm x 0.4 mm x 0.4 mm, or 1 mm x 1 mm x 1 mm. In some embodiments, the image sensors 1102A, 1102C may be no larger than or longer than the distal tip camera modules 1104A, 1104C.

[0220] Still refer to Figures 15 to 23, distal tip camera 1004 may include at least one of distal tip cameras 1004A to 1004D, optical fiber 1302, and / or a combination thereof. Image sensor 1102 may include at least one of image sensors 1102A, 1102C, optical fiber 1302, and / or a combination thereof.

[0221] Still refer to Figures 15 to 23 In one or more embodiments, the distal tip camera 1004 can include features such as biocompatibility, lead-free, autofocus, disposable, reusable, low noise, low power consumption, low heat, and / or low noise for convenience. The distal tip camera 1004 can generate color images, grayscale images, and / or a combination thereof.

[0222] Still refer to Figures 15 to 23 In some embodiments, the distal tip camera 1004 can include a working distance of up to 100 mm. In some embodiments, the distal tip camera 1004 can include a working distance of up to 50 mm. In some embodiments, the distal tip camera 1004 can include a working distance of up to 20 mm. In some embodiments, the distal tip camera 1004 can include a working distance of up to 10 mm. In some embodiments, the distal tip camera 1004 can include a working distance of up to 5 mm.

[0223] Figure 23A 、 Figure 23B and Figure 23C Device 10 is shown including a distal tip camera 1004 integrated into blocker 28 . Figure 23A The device 10 is shown with its tip portion circled at A, thereby Figure 23B and Figure 23C Detailed areas are indicated. Figure 23B shows a perspective view of the tip portion, and Figure 23C A side view of the tip portion is shown. Figure 23A 、 Figure 23B and Figure 23C In some embodiments, the device 10 may include a lens or sensor 1102 and a camera unit (e.g., a distal tip camera 1004) integrated into the blocker 28. In some embodiments, the blocker 28 may be molded around the distal tip camera 1004. The distal tip camera 1004 may also be attached to the blocker 28 via an adhesive, epoxy, and / or other suitable mechanism. The wire 1002 provides power and a communication link to the distal tip camera 1004. In some embodiments, the wire 102 may be sized such that the wire fits between two of the telescoping hypotubes (e.g., at Figure 9 extends or passes between two of the members 42A, 42B, 42C or 42D).

[0224] Figure 23D 、 Figure 23E and Figure 23F The device 10 is shown including a distal tip camera 1004 axially separated from (e.g., behind) the stopper 28. Figure 23D 、 Figure 23E and Figure 23F In an embodiment, the device 10 may include a distal tip camera 1004 and a lens 1102 mounted to a telescoping hypotube (e.g., Figure 9 The distal tip camera 1004 may be attached to the hypotube via adhesive, epoxy, welding, and / or other suitable mechanisms. Figure 23E Included are distal tip camera 1004 and lens or sensor 1102 in an angled configuration 1103 .

[0225] Figure 23G and Figure 23H An apparatus 10 is shown comprising a device mounted on a telescoping hypotube (e.g., Figure 9 The distal tip camera 1004, lens 1102 and wire 1002 are attached to one of the members 42A, 42B, 42C or 42D). The distal tip camera 1004 may be attached to the hypotube via adhesive, epoxy, welding and / or other suitable mechanisms. Figure 23G and Figure 23H (as well as Figures 23A to 23F ) embodiments, the device 10 may include a camera module housing 1106 that externally encloses the distal tip camera 1004, the lens 1102, and the wire 1002.

[0226] refer to Figures 15 to 23 (include 23A to 23H ), in some embodiments, the device (including the camera) comprises a total effective diameter of less than about 10 mm, or about 1 mm to about 10 mm, or about 1 mm to about 8 mm, or about 1 mm to about 5 mm, or about 1 mm to about 4 mm, or about 2 mm to about 4 mm, or about 1 mm to about 3 mm, or about 1.5 mm to about 3 mm, or about 1 mm to about 2.5 mm and / or less than about 3 mm.

[0227] Figure 24A system 2400 including the device 10 according to aspects of the disclosed embodiments is shown. The system 2400 may also include a distal tip camera 1004, a guide wire 1002, a light source 1022, and / or a monitor 2402 as described herein. The monitor 2402 may be operatively coupled to the distal tip camera 1004. In some embodiments, the system 2400 may also include one or more syringes 60 for injecting fluids, a syringe or tubing 36 fluidly connected to one or more syringes or tubing 36 (shown in FIG. Figures 3 to 5 2400 ), a power source 2410, a sterilization device, a sharps container (e.g., a biohazard sharps container), a drill 2404 (e.g., an otological drill and / or a diamond drill), and / or a laser 2406 (e.g., a KTP or CO2 otological laser) (not shown). In some embodiments, the system 2400 may include a microscope, an endoscope, and / or a fiberscope (not shown) (e.g., if the system 2400 does not have a distal tip camera 1004). The syringe 60 may include a "Luer-Lok TM The syringe 60 may include a "syringe" and may include a capacity of about 1 mL to about 100 mL, including various capacities and subranges therebetween, 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. The syringe 60 may include graduations of 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. The syringe 60 preferably and / or optionally complies with ISO 13485, and other applicable safety and quality standards.

[0228] Still refer to Figure 24 The pump 2408 can generate the desired flow and pressure conditions according to the present disclosure and can be integrated with the syringe 60. The pump 2408 may include 3500 syringe pump, and / or Harvard Apparatus 70-2000, and / or other designs, configurations, and arrangements (including pumps manufactured by other OEMs) may also be included, so long as the pump 2408 is capable of generating the desired flow and pressure conditions according to the present disclosure. The pump 2408 can accommodate a variety of syringe capacities, including from about 1 mL to about 100 mL. The pump 2408 may also accommodate various flow rates including about 1 mL / hr to about 50 mL / hr, or about 2 mL / hr to about 40 mL / hr, or about 3 mL / hr to about 25 mL / hr, or about 4 mL / hr to about 20 mL / hr, or about 5 mL / hr to about 15 mL / hr, or about 8 mL / hr to about 12 mL / hr, or about 0.5 mL / hr to about 15 mL / hr, or about 1 mL / hr to about 12 mL / hr, or about 2 mL / hr to about 10 mL / hr, or about 2.5 mL / hr to about 8 mL / hr, or about 3 mL / hr to about 7 mL / hr, or about 4 mL / hr to about 6 mL / hr. The pump 2408 may include a relative or gauge pressure operating range of about 0 psi to about 50 psi and may be able to accommodate back pressures ranging from about -300 mmHg to about +900 mmHg while providing the desired flow rate to the device.

[0229] Still refer to Figure 24 , the device 10 can be connected to the Luer lock 61 (e.g., "Luer-Lok TM A syringe, which may be integrated with the syringe 60 and / or pump 2408) is coupled to the syringe 60 to minimize air introduction during delivery of the fluid to the ear and to ensure proper connection with the tubing 36 (e.g., as Figure 1 、 Figure 3 、 Figure 6 and / or Figure 12As shown). The Luer lock 61 (or Luer connector) may include a custom sleeve insert to help degas the system (i.e., to help remove air from the system). The custom sleeve may be molded silicone (or other suitable material) and may be inserted into the inside of the Luer lock 61 (or connector). The custom sleeve may be generally cylindrical in shape with a central bore (or lumen) in which the end of the PEEK tubing 36 may be disposed. The central bore (or lumen) may include a conical inlet. The custom sleeve helps to occupy the "dead space" within the Luer lock 61 (or connector), minimizing the amount of air inside the Luer lock 61 (or connector). The Luer lock 61 may include a Luer lock and / or a Luer slip connector, and may include a sliding tip. In addition, the Luer lock 61 may include external threads connected to the syringe 60 that mate with internal threads connected to the needle 38, as well as other suitable leak-proof connectors and / or coupling configurations. The syringe 60 can be used to inject a fluid, such as a therapeutic fluid containing a therapeutic agent, which may be a small molecule or a biologic, such as an antibody or viral gene therapy. The syringe 60 can be packaged separately from other device components to accommodate device preparation. The syringe 60 can be sterilized. Device preparation can be performed outside the operating room (e.g., in a pharmacy). Device preparation can be performed within the operating room. Device preparation can be performed using a sterile area and / or sterilizing equipment. By including a distal tip camera 1004 on the device 10, the surgeon can see around corners, thereby avoiding the need to remove obstacles such as overhanging bone. In addition, using a delivery device 10 (or microcatheter) with an embedded distal tip camera 1004 allows the surgeon to puncture the round window, deliver the therapeutic fluid, and visualize the outer ear, middle ear, and / or inner ear with a single tool operation.

[0230] method

[0231] Figure 25 A method 2500 is shown for installing a device 10 (or microcatheter) and delivering a fluid (e.g., a therapeutic fluid) to the inner ear according to various aspects of an embodiment of the present invention. In some embodiments, the present disclosure describes a delivery method that utilizes minimally invasive, well-accepted surgical techniques to access the middle ear and / or inner ear through the external auditory canal. The procedure includes making an opening in the physical barrier between the middle ear and the inner ear at the oval window, and then using the delivery device 10 (or microcatheter) to deliver a therapeutic fluid (e.g., containing one or more biologics such as viral gene therapy for treating hearing impairment) through the round window membrane at a controlled flow rate and in a fixed volume. Figure 25 The surgical procedures are generally described as they apply to humans. However, similar methods and procedures are applicable to mice, rodents, and non-human primates, as described in the following paragraphs.

[0232] The delivery device 10 can be placed in the sterile area of the operating room, and the end of the tubing 36 can be removed from the sterile area and connected to a syringe 60 that has been loaded with the therapeutic fluid and installed in a pump. After the system 2400 is properly primed to remove any air, the needle 38 can be passed through the middle ear under visualization (surgical microscope, endoscope, and / or distal tip camera 1004). The needle 38 (or microneedle) can be used to pierce the RWM. The needle 38 can be inserted until the stopper 28 contacts the RWM. The device 10 can then be maintained in this position while the therapeutic fluid is delivered to the inner ear at a controlled flow rate. Once delivery is complete, the device 10 can be removed. The device 10 can be configured as a single-use, disposable product. In other embodiments, the device 10 can be configured as a multi-purpose sterilizable product, for example, with a replaceable and / or sterilizable needle subassembly 26. The single-use device 10 can be appropriately discarded (e.g., discarded in a biohazard sharps container) after administration is complete.

[0233] refer to Figure 25 , a surgical procedure or method 2500 for delivering a therapeutic fluid to the inner ear of a patient may include marking the ear to be treated with an indelible marker at step 2502. At step 2504, method 2500 may include inducing general anesthesia in the patient. At step 2506, method 2500 may include positioning the patient in a supine position (i.e., dorsal position) with the patient's head turned to the side so that the marked ear faces upward. At step 2508, method 2500 may include preparing the ear with an antiseptic (such as povidone-iodine, iodine-povidone, pyridamole, voracdin, perdin, and / or other suitable antiseptic) and covering the ear and surrounding area with a drape (e.g., covering the immediate area around the ear and / or otherwise forming a sterile barrier around the ear while allowing access to the ear to minimize infection and / or contamination risk). At step 2510, method 2500 may include applying lidocaine, norepinephrine, and / or other anesthetics and epinephrine to the ear canal in four quadrants. The lidocaine and norepinephrine may be precisely applied using a surgical microscope, an endoscope, and / or a distal tip camera 1004. Without limitation, the application of lidocaine and norepinephrine may include a composition having approximately 1% lidocaine and norepinephrine at a dilution of one in eight thousand (1:8,000). In some embodiments, the endoscopic surgeon may use a higher or lower concentration of lidocaine or norepinephrine, depending on the volume of the composition injected per injection and the desired total dose of lidocaine or norepinephrine. In some embodiments, the volume of the composition is less than 1 mL per injection.

[0234] Still refer to Figure 25, steps 2512, 2514, and 2516 describe steps for preparing the system 2400. The system preparation steps (2512, 2514, and 2516) may be performed concurrently with, before, and / or after, the patient preparation steps (i.e., steps 2502, 2504, 2506, 2508, and 2510). At step 2512, the method 2500 may include sterilizing the device 10, for example, via a sterile area (or, for example, via gamma irradiation or steam sterilization prior to packaging the device). At step 2514, the method 2500 may include connecting the tubing 36 to the proximal end 16 of the device 10. At step 2516, the method 2500 may include priming and flushing the system 2400 to ensure that air bubbles have been removed from all lines and that fluid suction is generated within the pump. The system 2400 may be primed and flushed using a therapeutic fluid as the flushing fluid. In one embodiment, a first amount of treatment 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 the device 10 until a droplet appears at the distal end 20 of the device. The second amount of treatment fluid (e.g., about 3 μL to about 7 μL or about 5 μL) is then pushed through the device 10 to ensure that the device is fully flushed. At step 2518, once the system and the patient are ready, method 2500 may include turning over the posterior tympanic membrane ear canal flap so that the device 10 can reach the oval window and the round window in the middle ear. At step 2520, method 2500 may include removing a limited amount of bone at the junction of the bony canal and the tympanic membrane using a micro-curette or drill. At step 2522, method 2500 may include forming a hole in the stapes base plate on the side opposite to the round window of the cochlea (or perforating the stapes base plate), thereby allowing appropriate drainage during delivery of the solution to the inner ear. The hole in the stapes base plate can be formed using an otological laser (e.g., a KTP or CO2 otological laser). At step 2524, method 2500 can include removing overhanging bone (e.g., a pseudomembrane or flange of overhanging bone) as needed to expose the round window. The overhanging bone can be removed using a 1 mm diamond drill bit. At step 2526, method 2500 can include activating distal tip camera 1004 (which can be embedded in device 10) to help insert device 10 into the external auditory canal and move the device along the external auditory canal.

[0235] Still refer to Figure 25At step 2528, method 2500 may include inserting device 10 into the external auditory canal. At step 2528, method 2500 may include piercing the round window with distal end 20 of device 10 (step 2530) and passing through the round window to a depth of no more than about 1 mm (e.g., to an insertion depth of about 0.7 mm to about 1 mm, or about 0.8 mm to about 0.95 mm, or about 0.85 mm to about 1.0 mm, or about 0.85 mm to about 0.95 mm). Stopper 28 may be concentrically positioned around bend 32 of needle 38 (or microneedle) in an appropriate position to ensure the correct insertion depth of needle 38 into the round window. In some embodiments, distal tip camera 1004 (or endoscope and / or surgical microscope) may be used by the surgeon (e.g., in conjunction with monitor 2402 or a display screen communicatively coupled to the distal tip camera) to ensure the device is inserted to the correct insertion depth (step 2532). Thus, the stopper 28 can be primarily used to ensure an insertion depth of no more than 1.0 mm, while the distal tip camera 1004 can be used to precisely position the device 10 before (and during) insertion of the needle 38 (or microneedle) into the round window. In other embodiments, the insertion depth can be greater than 1.0 mm and can include, for example, depths of approximately 1.1 mm, approximately 1.2 mm, approximately 1.3 mm, approximately 1.4 mm, approximately 1.5 mm, approximately 1.6 mm, approximately 1.7 mm, and other subranges therebetween. At steps 2528, 2530, and / or 2532, the method 2500 can include adjusting the angle or orientation of the device 10 as needed during the procedure. Thus, even if the angle of the tip 34 of the device 10 is fixed relative to the handle portion 12, the orientation of the tip 34 relative to the RWM can be adjusted on the fly based on the angle or range of angles at which the surgeon orients the device 10. At step 2534, the method 2500 can include flowing the therapeutic fluid through the device 10 at a selected flow rate for a selected duration.

[0236] Still refer to Figure 25In some embodiments, the flow rate (or infusion rate) may comprise a rate of about 30 μL / min, or about 25 μL / min to about 35 μL / min, or about 20 μL / min to about 40 μL / min, or about 20 μL / min to about 70 μL / min, or about 20 μL / min to about 90 μL / min, or about 20 μL / min to about 100 μL / min. In some embodiments, the selected duration (i.e., the time the therapeutic fluid flows) may be about 3 minutes, or about 2.5 minutes to about 3.5 minutes, or about 2 minutes to about 4 minutes, or about 1.5 minutes to about 4.5 minutes, or about 1 minute to about 5 minutes. In some embodiments, the total volume of therapeutic fluid flowing to the inner ear may be about 0.09 mL, or about 0.08 mL to about 0.10 mL, or about 0.07 mL to about 0.11 mL. In some embodiments, the duration of treatment may be less than one minute (e.g., from about 25 seconds to about 59 seconds, or from about 30 seconds to about 55 seconds, or from about 31 seconds to about 45 seconds). In some embodiments, the total volume of the therapeutic fluid is equal to from about 40% to about 50% of the volume of the inner ear. At step 2536, method 2500 may include monitoring the distribution of the therapeutic fluid (or therapeutic agent) within the inner ear, including the base, middle, and apex of the cochlea (e.g., via distal tip camera 1004, endoscope, and / or surgical microscope) to determine whether the insertion depth of device 10 within the round window should be adjusted (e.g., to be deeper or shallower). For example, in one or more embodiments, the cumulative volume may be monitored, while in other embodiments, a fluorescent agent may be added to the therapeutic fluid, which may then be excited and / or activated via optical fiber or distal tip camera 1004 so that the distribution of the therapeutic fluid to the inner ear can be visualized. At step 2538, method 2500 may include removing device 10. At 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 baseplate to create a functional closure of both (or either) areas while healing occurs over a subsequent period of time (e.g., about 24 hours to about 48 hours). At step 2542, method 2500 may include returning the posterior tympanic membrane canal flap to its original (biological) position. In some embodiments according to the present disclosure, 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 baseplate to create a functional closure of both (or either) areas while healing occurs over a subsequent period of time (e.g., about 24 hours to about 48 hours). Figure 25 Perform one or more steps in a different order than shown, and perform Figure 25 In some embodiments, one or more steps may be omitted and / or performed simultaneously with at least one other step.

[0237] Certain definitions

[0238] To make the present disclosure more readily understood, certain terms are first defined below. Additional definitions of the following terms and other terms are set forth throughout the specification.

[0239] Apparatuses, compositions, or methods described herein as “comprising” one or more specified elements or steps are open ended, meaning that the specified elements or steps are essential, but other elements or steps may be added within the scope of the composition or method. To avoid redundancy, it is also understood that any apparatus, composition, or method described as “comprising” (or “comprises”) one or more specified elements or steps also describes a corresponding, more limited composition or method “consisting essentially of” (or “consists essentially of”) the same specified elements or steps, meaning that the composition or method includes the specified essential elements or steps and may also include additional elements or steps that do not materially affect the basic and novel characteristics of the composition or method. It is also understood that any apparatus, composition, or method described herein as “comprising” (or “consisting essentially of”) the one or more specified elements or steps also describes a corresponding, more limited and closed composition or method “consisting of” (or “consists of”) the specified elements or steps, excluding any other unspecified elements or steps. In any composition or method disclosed herein, any designated essential element or step may be substituted for a known or published equivalent thereof.

[0240] As used herein, "a" or "an" with respect to a claim feature means "one or more" or "at least one".

[0241] As used herein, "biocompatible" refers to a material that does not cause significant damage to living tissue when placed in contact with such tissue (e.g., in vivo). In some embodiments, a material is "biocompatible" if it is easily applied 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 adding the material to cells in vitro results in less than or equal to 20% cell death, and / or administration of the material in vivo does not induce significant inflammation or other such side effects. In some embodiments, the materials used in the described devices and systems are biocompatible and have been tested to meet Class II biocompatibility requirements (e.g., devices with short residence times (less than 24 hours) and indirect blood pathways).

[0242] As used herein, "disease," "disorder," and / or "illness" refer to any disease, disorder, and / or condition that can be treated by accessing the inner ear. In some embodiments, the disease, disorder, and / or condition is a hearing impairment (such as hearing loss). In some embodiments, the disease, disorder, and / or condition is a balance disorder. In some embodiments, the disease, disorder, and / or condition is a tumor such as an inner ear tumor. In some embodiments, the disease, disorder, and / or condition is a tumor such as a vestibular schwannoma. Other diseases, disorders, and / or conditions include, but are not limited to, acoustic neuroma, age-related dizziness and imbalance, autoimmune inner ear disease, benign paroxysmal positional vertigo, bilateral vestibular hypofunction, CANVAS syndrome, and chloesteatoma.

[0243] As used herein, "therapeutic fluid" refers to a fluid composition comprising a therapeutic agent or a delivery form (e.g., a nucleic acid vector encoding a therapeutic agent) for providing a therapeutic agent to the inner ear. The therapeutic agent can be in any form, such as a small molecule or biological agent with the function of treating a disease or disorder (e.g., hearing disease, disorder) and / or illness, tumor, etc. In some embodiments, the therapeutic agent is a 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 microRNA. In some embodiments, the therapeutic agent is a therapeutic short hairpin RNA. In some embodiments, the therapeutic agent is a therapeutic CRISPR / Cas system including a Cas protein and a guide molecule (e.g., a guide RNA). In some embodiments, the therapeutic agent is delivered to the inner ear in the treatment fluid. In some embodiments, the therapeutic agent is encoded by a delivery form (e.g., a nucleic acid vector delivered to the inner ear in the treatment fluid). In some embodiments, the therapeutic agent is formulated with one or more pharmaceutically acceptable carriers. In some embodiments, the active agent is present in a treatment regimen in an amount suitable for administration as a unit dose that exhibits a statistically significant probability of achieving a predetermined therapeutic effect when administered to a population of interest. In some embodiments, the therapeutic fluid may be particularly suitable for administration via injection, i.e., the therapeutic fluid is, for example, an aqueous or non-aqueous solution or suspension.

[0244] As used herein, the term "pharmaceutically acceptable," such as might be used with respect to a carrier used to formulate a therapeutic fluid as disclosed herein, means that the carrier is compatible with the other ingredients of the fluid composition and not deleterious to the recipient thereof.

[0245] As used herein, the term "treat" (also referred to as "treatment" or "treating") refers to any administration of a therapeutic agent (also referred to as "therapy") that partially or completely alleviates, ameliorates, eliminates, reverses, alleviates, inhibits, delays the onset of, reduces the severity of, and / or reduces the incidence of one or more symptoms, features, and / or causes of a particular disease, disorder, and / or condition. In some embodiments, such treatment may be directed to patients who do not show signs of the relevant disease, disorder, and / or condition and / or patients who only show early signs of the disease, disorder, and / or condition. Alternatively or in addition, such treatment may be directed to patients who show one or more established signs of the relevant disease, disorder, and / or condition. In some embodiments, treatment may be directed to patients who have been diagnosed with the relevant disease, disorder, and / or condition. In some embodiments, treatment may be directed to patients known to have one or more susceptibility factors that are statistically associated with an increased risk of developing a given disease, disorder, and / or condition. In some embodiments, the patient may be a human.

[0246] As used herein, the term "substantially" refers to the qualitative condition of exhibiting the full or nearly full extent or degree of a characteristic or property of interest.

[0247] Equivalent solutions

[0248] It is to be understood that while the disclosure has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the claims. Other aspects, advantages, and modifications are within the scope of the claims.

[0249] This specification uses examples to disclose the present invention, including the best mode, and also enables any person skilled in the art to practice the embodiments of the present invention, including making and using any device or system, and performing any method combined. The scope of patent protection for the embodiments of the present invention is defined by the claims and may include other examples that occur to those skilled in the art. If other such examples include structural elements that are the same as the literal meaning of the claims, or if such examples include equivalent structural elements that are not substantially different from the literal meaning of the claims, such examples are also intended to be within the scope of the claims.

Claims

1. A device for delivering fluid to an ear, the device comprising: a handle portion comprising a proximal end and a distal end; a needle subassembly coupled to the distal end of the handle portion, the needle subassembly comprising: (1) a bent needle and (2) a stopper disposed at the distal end of the needle subassembly, the stopper comprising a stopper tapered portion having a radius that gradually increases from a proximal end of the stopper toward a distal end of the stopper; as well as a tube coupled to the proximal end of the handle portion, wherein the bending needle extends through the handle portion and is directly fluidly connected to the tubing.

2. The device of claim 1 further comprising a telescoping support coupled to the proximal end of the needle subassembly.

3. The device of claim 2, wherein the distal end of the handle is coupled to a proximal end of the telescoping support.

4. The apparatus of claim 2 or 3, wherein the telescopic support comprises a plurality of nested hypotubes.

5. The device of any one of claims 1 to 3, wherein the bending needle comprises: an angled tip for piercing at least one membrane; as well as Bending part.

6. The device according to any one of claims 1 to 3, comprising: A strain relief feature is coupled to the proximal end of the handle portion.

7. The device of any one of claims 1 to 3, comprising a camera, wherein the camera comprises a distal tip camera, and Wherein the distal tip camera is positioned within the needle subassembly.

8. The device of any one of claims 1 to 3, wherein the tube is coupled to the bending needle within the hollow interior of the handle portion.

9. The apparatus of claim 8, wherein the tubing comprises an inner diameter of 0.005 inches to 0.01 inches.

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

11. The device of claim 5, wherein the angle is 20 degrees to 70 degrees.

12. The device of claim 5, wherein the angle is 30 degrees.

13. The device of claim 5, wherein the angle is 55 degrees.

14. The device of any one of claims 1 to 3, wherein the bending needles comprise a gauge in the range of 10 to 35.

15. The device of any one of claims 1 to 3, wherein the bending needle comprises stainless steel.

16. The device of any one of claims 1 to 3, comprising an adhesive disposed on the proximal and distal ends of the handle portion.

17. The device of claim 5, comprising a stopper coupled to the bent needle, wherein the stopper is shaped and sized to be positioned within the inner ear and to control the distance that the angled tip protrudes into the cochlea.

18. The device of any one of claims 1 to 3, wherein the barrier comprises a cylinder-disc shape.

19. The device of any one of claims 1 to 3, wherein the stopper is molded into place on the bending needle, and wherein the stopper prevents the bending needle from being inserted into at least one membrane beyond a desired amount.

20. The device of claim 5, wherein the stopper is positioned at a distance of 0.2 mm to 1.2 mm from the distal end of the angled tip.

21. The device of any one of claims 1 to 3, wherein the barrier comprises a diameter of 0.2 mm to 1.2 mm.

22. The device of any one of claims 1 to 3, wherein the stopper comprises a height of 0.2 mm to 1.0 mm.

23. The apparatus of claim 4, wherein each hypotube in the plurality of nested hypotubes comprises 10 to 30 models.

24. The apparatus of claim 4, wherein each hypotube in the plurality of nested hypotubes comprises stainless steel.

25. The device of claim 2 or 3, wherein the handle portion further comprises a tapered portion disposed at the distal end of the handle, the telescopic support being coupled to the tapered portion, wherein the handle tapers downwardly to a first distal end such that a second proximal end of the telescopic support is coupled to the first distal end.

26. The device of claim 2 or 3, wherein the telescoping support tapers from an outer diameter of 0.2 inches or less at a proximal end to an outer diameter of 0.01 inches or more at a distal end.

27. The device of any one of claims 1 to 3, wherein the handle portion includes machined grooves for tactile feel and control.

28. The device of claim 17, wherein the handle portion is shaped and sized to facilitate placement into the inner ear.

29. The device of claim 6, wherein the strain relief feature comprises a layered extrusion.

30. The device of claim 6, wherein the strain relief feature prevents kinking and / or deformation of the tubing.

31. The device of claim 8, wherein the tubing is coupled to the bending needle via a compression fit.

32. The apparatus of claim 8, wherein the tubing comprises polyetheretherketone (PEEK).

33. The apparatus of claim 8, wherein the tubing comprises an inner diameter of 0.003 inches to 0.01 inches.

34. The apparatus of claim 8, wherein the tubing comprises an outer diameter of 1 / 64 inch to 1 / 16 inch.

35. The apparatus of claim 8, wherein the tubing comprises a length greater than 20 inches.

36. The device of any one of claims 1 to 3, wherein the device is sterile and / or biocompatible.

37. The device of claim 5, wherein the angled tip protrudes from the bent portion of the bent needle to form an outlet for dispensing fluid.

38. The device of claim 17, wherein the stopper is positioned around a stopper anchoring groove disposed within the bending needle.

39. The device of claim 2, further comprising an annular band disposed at an interface between the telescoping support and the handle portion.

40. The device of claim 6, further comprising at least one machined barb disposed at the proximal end of the handle portion, wherein the at least one machined barb interfaces with the strain relief feature and prevents axial movement between the handle portion and the strain relief feature.

41. The device of claim 1, wherein the barrier further comprises a chamfer disposed along a distal end of the barrier.

42. A system comprising the device of any preceding claim and a sterile syringe fluidly coupled to the tubing.

43. The system of claim 42, comprising a pump.

44. The system of claim 43, wherein the pump controls the flow rate of fluid through any of the devices at a rate of 10 μL / min to 60 μL / min.

45. A delivery system comprising: A delivery device, comprising: a distal end; and a stopper disposed at the distal end of the delivery device, the stopper comprising a stopper tapered portion having a radius that gradually increases from a stopper proximal end toward a stopper distal end; a distal tip camera disposed at the distal end of the delivery device, the distal tip camera comprising an image sensor; and A monitor is operatively coupled to the distal tip camera, wherein the monitor displays information received from the distal tip camera.

46. The system of claim 45, wherein the barrier is transparent.

47. The system of claim 45, wherein the blocker includes a transparent portion for the distal tip camera to see through the blocker.

48. The system of claim 45, wherein the distal tip camera is disposed above a front surface of the blocker, the front surface of the blocker facing the target.

49. The system of claim 48, wherein the target is a portion of an ear.

50. The system of claim 47, wherein the distal tip camera is embedded within the blocker.

51. The system of claim 47, wherein the distal tip camera is positioned behind the blocker.

52. The system of claim 45, further comprising a wire operatively coupled between the distal tip camera and the monitor.

53. The system of claim 45, wherein the distal tip camera includes an autofocus feature.

54. The system of claim 45, wherein the distal tip camera comprises at least one of a cubic shape, a slice shape, a cylindrical shape, and combinations thereof.

55. The system of claim 45, wherein the image sensor comprises a field of view of 90° to 150°.

56. The system of claim 45, wherein the image sensor comprises at least one of: a cubic shape having dimensions of up to 10 mm x 10 mm and a height of up to 100 mm; and a cylindrical shape comprising an outer diameter of up to 10 mm and a length of up to 100 mm.

57. The system of claim 45, wherein the image sensor comprises an image array capable of capturing at least 10 x 10 pixel resolution video at a frame rate of at least 5 frames per second (fps).

58. The system of claim 45, wherein the image sensor comprises an image area of at most 10 mm x 10 mm.

59. The system of claim 45, wherein the image sensor comprises an optical format up to 10 mm and a pixel size up to 10 μm.

60. The system of claim 45, comprising a processor operatively coupled to the image sensor.

61. The system of claim 45, comprising a driver package and / or a software package.

62. The system of claim 45, comprising at least one light source.

63. The system of claim 45 comprising optical fiber.

64. The system of any one of claims 45-63, wherein the blocker further comprises a chamfer disposed along a distal end of the blocker.

65. A distal tip camera system, comprising: an image sensor disposed at a distal end of a needle, the distal end of the needle comprising a stopper including a stopper tapered portion having a radius that gradually increases from a stopper proximal end toward a stopper distal end; a wire operatively coupled to the image sensor; a processor operatively coupled to the image sensor; as well as A monitor is operatively coupled to the processor to display information captured by the image sensor and processed by the processor.

66. The distal tip camera system of claim 65, wherein the blocker further comprises a chamfer disposed along a distal end of the blocker.

67. A device for delivering fluid to an ear, the device comprising: a handle portion comprising a proximal end and a distal end; a telescoping support coupled to the distal end of the handle portion; a needle subassembly coupled to a distal end of the telescoping support, the needle subassembly including a bent needle, the distal end of the needle subassembly including a stopper including a stopper tapered portion having a radius that gradually increases from a proximal end of the stopper toward a distal end of the stopper; as well as A tube is coupled to the proximal end of the handle portion.

68. The device of claim 67, wherein the blocker further comprises a chamfer disposed along a distal end of the blocker.

69. A system for delivering a therapeutic fluid to a portion of an inner ear of a patient, the system comprising: Device for opening the posterior tympanic membrane ear canal flap; a device for creating an opening in the stapes footplate of the inner ear; and a fluid delivery device comprising a needle positioned at a distal end of the fluid delivery device, wherein the needle is configured to puncture a round window of an inner ear, the distal end of the needle comprising a stopper, the stopper comprising a stopper tapered portion having a radius that gradually increases from a proximal end of the stopper toward a distal end of the stopper; wherein the fluid delivery device is configured to be positioned within the round window at a desired insertion depth; and wherein the fluid delivery device is configured to deliver the therapeutic fluid to the inner ear.

70. The system of claim 69, further comprising: at least one of a distal tip camera, an endoscope, and a surgical microscope, wherein at least one of the distal tip camera, the endoscope, and the surgical microscope is activated before the needle punctures the round window; as well as wherein at least one of the distal tip camera, the endoscope, and the surgical microscope is configured to monitor at least one of the flow rate of the therapeutic fluid and the distribution of the therapeutic fluid in the inner ear via at least one of the distal tip camera, the endoscope, and the surgical microscope before the needle punctures the round window.

71. The system of claim 70, comprising a distal tip camera, wherein the distal tip camera is activated before the needle punctures the round window, wherein the distal tip camera is communicatively coupled to at least one monitor viewable by a surgeon.

72. The system of claim 69, wherein the means for everting the posterior tympanic canal flap comprises at least one of a micro-curette and a drill for incising the posterior tympanic canal.

73. The system of claim 69, further comprising: means for preparing and draping the ear prior to everting the posterior tympanic membrane ear canal flap, wherein the patient is positioned prior to preparing and draping the ear; means for inducing anesthesia prior to positioning said patient; as well as Device for marking the ear prior to induction of anesthesia.

74. The system of claim 69, further comprising: Upstream pump; a tube for connecting the fluid delivery device to an upstream pump, wherein the tube is connected before the posterior tympanic membrane ear canal flap is unfolded; and means for sterilizing the fluid delivery device prior to everting the posterior tympanic membrane ear canal flap; The system is irrigated before the posterior tympanic membrane ear canal flap is unfolded.

75. The system of claim 69, wherein the therapeutic fluid comprises at least one viral gene therapy.

76. The system of claim 69, wherein: The fluid delivery device is removed from the inner ear after the therapeutic fluid has flowed therethrough; and At least one skin treatment is applied to at least one of the round window membrane and the stapes baseplate after removing the fluid delivery device.

77. The system of claim 76, further comprising means for returning the posterior tympanic canal flap to an original position after application of at least one skin treatment.

78. The system of claim 69, further comprising a device for removing bone from the junction of the bony canal and the tympanic membrane and / or removing bone overhanging the pseudomembrane after flipping open the posterior tympanic canal flap, wherein the device for removing bone comprises at least one of a diamond drill bit and an otological drill bit.

79. The system of claim 69, wherein the means for creating an opening in the stapes base plate comprises an otologic laser.

80. The system of claim 69, further comprising means for applying at least one of an anesthetic and epinephrine to the patient's ear canal prior to unfolding the posterior tympanic canal flap.

81. The system of claim 73, wherein the means for preparing the ear further comprises means for applying at least one antimicrobial agent to the ear, wherein the at least one antimicrobial agent comprises at least one of povidone iodine, iodine povidone, pyridamole, vorcadin, and peldin.

82. The system of claim 76, wherein the at least one skin treatment comprises at least one of sodium hyaluronate and hyaluronic acid.

83. The system of claim 69, wherein the desired insertion depth comprises a depth of 0.7 mm to 1.0 mm.

84. The system of claim 69, wherein the fluid delivery device is configured to deliver the therapeutic fluid to the inner ear at a flow rate of 20 μL / min to 100 μL / min, wherein the fluid delivery device is configured to deliver a total volume of therapeutic fluid in the range of 0.07 mL to 0.11 mL to the inner ear, and wherein the fluid delivery device is configured to deliver the therapeutic fluid over a duration of 0.5 minutes to 5 minutes.

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