Apparatus and method for targeted delivery of materials - Patents.com

Abstract

Disclosed herein are embodiments of devices and systems for applying a bioadhesive to a retina, which can include an outer sleeve having a proximal end, a distal end, a passageway extending along the length of the elongate body and an opening at the distal end of the elongate body, an applicator tip including an elongate body having a proximal end and a distal end and an applicator portion coupled to the distal end of the elongate body, and a substance delivery lumen extending along the length of the device and through which the bioadhesive can pass so that the bioadhesive can be applied to at least the applicator portion of the applicator tip. Some embodiments of the device can further include a source of bioadhesive in fluid communication with at least the substance delivery lumen.

Description

[Technical field]

[0001] Priority Claims and Incorporation by Reference This application claims the benefit under 35 U.S.C. §119(e) of U.S. Application No. 63 / 049,044, filed July 7, 2020, and U.S. Application No. 63 / 050,695, filed July 10, 2020. The contents of each of these priority applications are incorporated herein by reference in their entirety for all purposes as if fully set forth herein. Any application in which a foreign or domestic priority claim is identified in an Application Data Sheet filed with this application is incorporated herein by reference in its entirety and made a part hereof.

[0002] Field The devices and methods disclosed herein relate to the targeted delivery of substances to tissue surfaces, such as the delivery and application of bioadhesives to retinal tissue. [Background technology]

[0003] background Existing methods for treating macular holes and retinal detachments associated with retinal discontinuities such as tears and breaks include the use of perfluorocarbons, lasers, cryotherapy, gas bubble injection, and silicone oil. The use of perfluorocarbons to push fluid out of the subretinal space can lead to unintended migration of perfluorocarbon fluid into the subretinal space, which can lead to loss of vision if located at the central macula. If perfluorocarbon fluid is not completely removed from the vitreous space, it can cause related visual phenomena that can be uncomfortable for the patient. The use of lasers and cryotherapy can result in the formation of permanent retinal scar tissue and contribute to the formation of epiretinal membranes and epiretinal scar tissue. The use of gas bubble injection can lead to restrictions in the patient's activities and can cause complications such as increased intraocular pressure and cataracts. Similarly, silicone oil can be problematic because it can cause complications such as increased intraocular pressure, necessitating a second surgery for removal, and because residual oil bubbles often remain after removal attempts that can disrupt the patient's vision.

[0004] Existing methods for treating leaky eye wall discontinuities, such as incisions, scleral incisions, and tears, include sutures and commercially available bioadhesives. Sutured discontinuities may continue to leak. Sutures may cause ocular irritation, pain, and tearing, and may also cause local tissue reactions, including episcleral and conjunctival edema and inflammation. Summary of the Invention [Problem to be solved by the invention]

[0005] One difficulty with some bioadhesives is that they may cause toxicity. Another difficulty is that it may be difficult to apply the bioadhesive to non-pendant ocular surfaces, both inside and outside the eye, due to the effect of gravity on the bioadhesive as it leaves the tip of the bioadhesive delivery device. For example, in eyes with retinal breaks at the lateral or superior locations of the eye, gravity may make it difficult to apply the bioadhesive to the retinal break, as gravity may cause the bioadhesive to drip or drip as soon as it is expelled from the applicator, preventing accurate application to the retinal discontinuity. The same problem occurs when attempting to apply liquid or viscous materials to the lateral and inferior exterior surfaces of the eye. Another difficulty with bioadhesives is that they may be difficult to apply to large discontinuities in the retina and other ocular surfaces, as well as tissue discontinuities with irregularly shaped edges or edges at different heights. The challenge of applying the bioadhesive to retinal discontinuities is even more difficult when attempted using a transscleral inferior retinal approach. [Means for solving the problem]

[0006] Overview of Some Exemplary Embodiments Each of the systems, methods, and apparatuses of the present disclosure has several innovative aspects, implementations, or aspects, no single one of which alone contributes to the desired attributes disclosed herein.

[0007] Disclosed herein are embodiments of devices and systems for applying a bioadhesive to a retina, the embodiments including an outer sleeve having a proximal end, a distal end, a passageway extending along the length of the elongate body and an opening at the distal end of the elongate body, an applicator tip including an elongate body having a proximal end and a distal end and an applicator portion coupled to the distal end of the elongate body, and a substance delivery lumen extending along the length of the device and through which the bioadhesive can be passed so that the bioadhesive can be applied to at least the applicator portion of the applicator tip. Some embodiments of the device may further include a source of bioadhesive in fluid communication with at least the substance delivery lumen.

[0008] Any of the embodiments of the devices, systems, and methods disclosed herein may, in further embodiments, include any of the following features, components, and / or details: the applicator tip is configured to move between a first position in which the applicator portion is housed within the outer sleeve and a second position in which the applicator tip is located past an opening at a distal end of the outer sleeve; the applicator portion may have a first width when the applicator portion is in the first position and a second width when the applicator portion is in the second position, the second width being substantially greater than the first width; the substance delivery lumen being a passageway extending through at least the elongate body of the applicator tip; the substance delivery lumen may include a separate cannula disposed inside the outer sleeve and extendable and retractable relative to the outer sleeve; the substance delivery lumen may be axially fixed relative to the outer sleeve and adapted to apply a bioadhesive substance along at least a portion of the length of the applicator portion as the applicator portion is advanced distally. the applicator portion may have an opening adjacent an end of the outer sleeve to allow exudation onto the applicator portion; the device includes a handle coupled to a proximal end of the outer sleeve; the applicator portion may be biased such that a first side portion of the applicator portion curls towards a second side portion when the applicator tip is pulled proximally back into the outer sleeve; the elongated body of the applicator tip extends through the outer sleeve to at least the proximal end of the device; the elongated body of the applicator tip may be integrally formed with the applicator portion; the applicator portion may be non-removably coupled to the elongated body of the applicator tip; the applicator portion may be configured to be removed from the patient's body together with the device; the applicator portion may be configured to be moved to a first position before the device is removed from the patient's body; the applicator portion may be biased to collapse into the passage of the outer sleeve when the applicator portion is pulled proximally back into the outer sleeve;The applicator portion may include one or more of: the applicator portion may be biased such that a first side portion of the applicator portion folds toward a second side portion when the applicator tip is pulled proximally back into the outer sleeve; the applicator portion may be biased such that a first side portion of the applicator portion folds toward a second side portion when the applicator tip is pulled proximally back into the outer sleeve; and / or a passageway through at least the elongate body of the applicator tip communicates with an opening at a proximal end of the applicator portion; in any combination with any other features, components and / or details of any other embodiment disclosed herein;

[0009] Any of the embodiments of the devices, systems, and methods disclosed herein may, in further embodiments, include any of the following features, components, and / or details: a passageway through at least the elongate body of the applicator tip communicating with a plurality of openings passing through a first surface of the applicator portion; the applicator portion may have an asymmetric shape such that a first side portion located on one side of an axial centerline of the applicator portion may have a different shape than a second side portion located on the other side of the applicator portion, the first and second sides being divided by an axial centerline of the applicator portion; the applicator portion may have an asymmetric shape such that a first length of the first side portion located on one side of the axial centerline of the applicator portion may be longer than a second length of the second side portion located on a second side of the axial centerline of the applicator portion; the first side portion may have a first transition portion having a first axial length and the second side portion may have a first transition portion having a first axial length and a second transition portion having a first axial length and a second transition portion having a second ... first axial length and a The applicator portion may include one or more of: a second transition portion having a second axial length, the first length of the first transition portion being smaller than the second length of the second transition portion; the applicator portion may have an asymmetric width; the applicator portion may have an asymmetric thickness in the width direction such that a thickness profile of the applicator portion at a first side of the applicator portion may be different from a thickness profile of the applicator portion at a second side of the applicator portion; the portion on the first side of the applicator portion may be softer than the portion on the second side; and / or the applicator portion may be configured such that when the applicator portion is pulled back into the outer sleeve, the portion on the first side contracts before the portion on the second side contracts; the applicator portion may have an asymmetric width and an asymmetric thickness; in any combination with any other features, components, and / or details of any other embodiment disclosed herein.

[0010] Any embodiment of the devices, systems, and methods disclosed herein can, in further embodiments, include one or more of the following features, components, and / or details: the outer sleeve can have a notch at a distal end of the outer sleeve; the outer sleeve can have a notch at a distal end of the outer sleeve configured to facilitate contraction or reduction in size of the applicator portion as the applicator portion is retracted into the distal end of the outer sleeve; the notch can be generally "v" shaped or can have a tapered shape that narrows in the proximal direction; and / or the notch can be generally "u" shaped or can have a uniform width and a rounded end at the proximal end of the notch; in any combination with any other features, components, and / or details of any other embodiment disclosed herein.

[0011] Disclosed herein are embodiments of devices and systems for applying a substance to a tissue surface including a cannula and an applicator tip, the cannula having a proximal end, a distal end, and a passageway extending along the length of the cannula. In some embodiments, the applicator tip can include an elongate body having a proximal end and a distal end, an applicator portion coupled to the distal end of the elongate body, a passageway through at least the elongate body of the applicator tip, a handle coupled to the proximal end of the cannula, and a source of substance in fluid communication with the passageway extending along at least the length of the elongate body of the applicator tip.

[0012] Any of the embodiments of the devices, systems, and methods disclosed herein may, in further embodiments, be configured to include any of the following features, components, and / or details: the applicator tip may be configured to move along a length of the cannula passage between a first position in which the applicator portion is contained within the cannula and a second position in which the applicator tip extends past the distal end of the cannula; the applicator portion may have a first width when the applicator portion is in the first position and a second width when the applicator portion is in the second position, the second width being substantially greater than the first width; the applicator portion may be biased to collapse within the cannula passage when the applicator tip is retracted proximally back into the cannula; the substance may be a bioadhesive; the tissue may include ocular tissue; the applicator portion may be biased to collapse within the cannula passage when the applicator tip is retracted proximally back into the cannula; the applicator portion may be biased such that the first side portion of the applicator portion curls toward the second side portion when the applicator tip is pulled proximally back into the cannula; the applicator portion may be biased such that the first side portion of the applicator portion folds toward the second side portion when the applicator tip is pulled proximally back into the cannula; a passageway through at least the elongated body of the applicator tip communicating with an opening at a proximal end of the applicator portion; and / or a passageway through at least the elongated body of the applicator tip communicating with a plurality of openings through a first surface of the applicator portion; in any combination with any other features, components, and / or details of any other embodiment disclosed herein.

[0013] Disclosed herein are methods of treating a defect in retinal tissue that include advancing an apparatus for applying a bioadhesive toward the defect, covering at least a portion of an applicator tip of the apparatus with the bioadhesive, advancing the applicator tip past a distal end of an outer sleeve of the apparatus, and transferring the bioadhesive from the applicator tip of the apparatus to the defect. In some embodiments, the method can further include rolling or folding the applicator tip to a smaller size by retracting the applicator tip into the outer sleeve. [Brief description of the drawings]

[0014] [Figure 1] 1 illustrates a top view of an embodiment of a device for applying a substance to a surface of an object, showing the device in a second or extended state. [Diagram 2] 2 illustrates a side view of the embodiment of the device shown in FIG. 1, showing the device in a second or deployed state. [Diagram 3] FIG. 2 illustrates a side view of the embodiment of the device shown in FIG. 1, showing the device in a first or retracted state. [Figure 4] 2 illustrates an end view of the embodiment of the device shown in FIG. 1, showing the device in a first or retracted state. [Diagram 5] 1 illustrates an end view of another embodiment of a device, showing the device in a first or retracted state. [Figure 6] 13 shows a top view of another embodiment of an applicator. [Figure 7A] 1 illustrates a cross-sectional view of another embodiment of a device for applying a substance to a surface of an object, showing the device in a second or deployed state. [Figure 7B] 1 illustrates a cross-sectional view of another embodiment of a device for applying a substance to a surface of an object, showing the device in a second or deployed state. [Figure 8A] 1 illustrates a non-limiting example of a system or device as described herein. [Figure 8B] 1 illustrates a non-limiting example of a system or device as described herein. [Figure 8C] 1 illustrates a non-limiting example of a system or device as described herein. [Figure 9] 1 shows an example of a cannula with fibers or wires for light or cauterization. [Figure 10] 1 illustrates a side view of another embodiment of a device for applying a substance to a surface of an object, showing the device in a second or extended state. [Figure 11] FIG. 11 illustrates a side view of the embodiment of the device shown in FIG. 10, again showing the device in a second or extended state. [Figure 12] FIG. 1 is a side view of one embodiment of a device for applying a substance to a surface surgically advanced into an eye, showing the applicator portion in a retracted state. [Figure 13] FIG. 13 is a side view of the device shown in FIG. 12 surgically advanced into the eye, showing the applicator portion in an extended, deployed state. [Figure 14] FIG. 13 is a side view of another embodiment of an apparatus for applying a substance to a surface surgically advanced into an eye, showing a delivery cannula retracted within an outer cannula. [Figure 15] FIG. 15 is a side view of the embodiment of the device shown in FIG. 14, showing the delivery cannula extended over a portion of the applicator portion. [Figure 16] FIG. 15 is a side view of the embodiment of the device shown in FIG. 14, showing the applicator portion at least partially covered with a substance. [Figure 17] 15 is a side view of the embodiment of the device shown in FIG. 14, showing the applicator portion transferring a substance to a tissue defect in the eye. [Figure 18A] FIG. 13 is a perspective view of the end of an embodiment of a cannula that can be used with any of the embodiments of the device disclosed herein. [Figure 18B]18B is a cross-sectional view of the embodiment of the cannula shown in FIG. 18A taken through line 18B-18B in FIG. 18A. [Figure 18C] FIG. 18B is a top view of the embodiment of the cannula shown in FIG. 18A. [Figure 19A] FIG. 13 is a perspective view of the end of another embodiment of a cannula that can be used with any of the embodiments of the device disclosed herein. [Figure 19B] 19B is a cross-sectional view of the embodiment of the cannula shown in FIG. 19A taken through line 19B-19B in FIG. 19A. [Figure 19C] FIG. 19B is a top view of the embodiment of the cannula shown in FIG. 19A. [Figure 20A] FIG. 13 is a top view of the end of another embodiment of a cannula that can be used with any of the embodiments of the device disclosed herein. [Figure 20B] FIG. 13 is a top view of the end of another embodiment of a cannula that can be used with any of the embodiments of the device disclosed herein. [Figure 20C] FIG. 13 is a top view of the end of another embodiment of a cannula that can be used with any of the embodiments of the device disclosed herein. [Figure 21] FIG. 13 is a top view of an embodiment of an applicator that can be used with any of the device embodiments disclosed herein. [Figure 22] FIG. 13 is a top view of another embodiment of an applicator that can be used with any of the device embodiments disclosed herein. [Diagram 23] FIG. 13 is a top view of another embodiment of an applicator that can be used with any of the device embodiments disclosed herein. [Figure 24] FIG. 13 is a top view of another embodiment of an applicator that can be used with any of the device embodiments disclosed herein. [Diagram 25] FIG. 25 is a cross-sectional view of an embodiment of an applicator portion that can be used in any embodiment of the device disclosed herein, taken through line 25-25 in FIG. 21, where the cross-section is therefore perpendicular to the axial centerline of the applicator. [Figure 26] FIG. 2 is a cross-sectional view of another embodiment of an applicator portion that can be used in any embodiment of the device disclosed herein, the cross-section being perpendicular to the axial centerline of the applicator. [Figure 27] FIG. 2 is a cross-sectional view of another embodiment of an applicator portion that can be used in any embodiment of the device disclosed herein, the cross-section being perpendicular to the axial centerline of the applicator. [Figure 28] FIG. 2 is a cross-sectional view of another embodiment of an applicator portion that can be used in any embodiment of the device disclosed herein, the cross-section being perpendicular to the axial centerline of the applicator. [Figure 29] FIG. 2 is a cross-sectional view of another embodiment of an applicator portion that can be used in any embodiment of the device disclosed herein, the cross-section being perpendicular to the axial centerline of the applicator. [Diagram 30] FIG. 13 is a perspective end view of another embodiment of a delivery device showing the applicator in a retracted, folded position and the substance delivery cannula in a retracted position. [Diagram 31] 31 is a perspective end view of the embodiment of the delivery device shown in FIG. 30, showing the applicator portion in a partially advanced position and in an unfolded state. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] In the following detailed description, reference is made to the accompanying drawings, which form a part of the following detailed description. In the drawings, similar symbols typically refer to similar components unless the context dictates otherwise. The exemplary embodiments described in the detailed description, drawings, and claims are not meant to be limiting. Other embodiments may be utilized, and other changes may be made, without departing from the spirit or scope of the subject matter presented herein. It will be readily understood that the aspects of the present disclosure, as generally described herein and illustrated in the drawings, can be arranged, substituted, combined, separated, and designed in a wide variety of different configurations, all of which are expressly contemplated herein.

[0016] There is a need in the art for problem-free and easy-to-use devices and methods for applying therapeutic substances to ocular or other biological tissues. Disclosed herein are systems, devices, and methods for applying substances to surfaces, such as, but not limited to, applying biological substances to tissue surfaces. Some examples of applications of any of the devices and methods disclosed herein include, but are not limited to, applying biological substances such as bioadhesives to ocular tissues, such as for retinal breaks, holes, or detachments, applying biological substances such as bioadhesives to sclera, conjunctiva, and cornea, applying biological substances such as bioadhesives to seal perforations or breaks in gastrointestinal and colonic tissues, and the like. However, embodiments of the devices and methods disclosed herein are not limited to delivery of therapeutic substances or to ophthalmic, medical, or biological applications. The devices and methods disclosed herein can be used to deliver any desired or suitable material in any desired application, such as biological, non-biological, mechanical, or other.

[0017] 1 and 2 show top and side views, respectively, of one embodiment of a device 100 (also referred to herein as a delivery device) for applying a substance 101 to a surface of an object. In some embodiments, the device 100 can include a cannula or outer sleeve 102 (also referred to herein as an elongate body or outer sheath), an inner sleeve 104 (also referred to herein as an inner cannula) having a lumen or passageway 105 therein through which the substance 101 can be advanced, and an applicator 106 (also referred to herein as an applicator tip) coupled to the inner sleeve 104. The outer sleeve 102 can be configured to provide additional rigidity and maneuverability to at least a portion of the inner sleeve 104 and the applicator 106 to facilitate or improve a user's control of the device 100 during application of the substance 101.

[0018] The inner sleeve 104 can have a proximal end 104a (not shown) and a distal end 104b. The passageway 105 can extend from the proximal end 104a to the distal end 104b of the inner sleeve 104. As shown, an applicator 106 can be coupled to the distal end 104b of the inner sleeve 104.

[0019] The cannula may optionally be flexible, semi-rigid, or rigid and may be formed from any suitable material, including metal alloys, polymeric materials, etc. The system may optionally be configured without an outer sleeve 102, in which case the inner sleeve 104 and applicator 106 are sufficiently rigid and maneuverable such that the outer sleeve 102 is not necessary.

[0020] In any of the embodiments disclosed herein, the applicator 106 and / or other components may be preloaded onto the cannula or outer sleeve 102 such that the applicator 106 does not need to be advanced to the proximal end of the cannula 102 after the cannula 102 has been advanced to the target location. Optionally, the device 100 may be configured to advance the applicator 106 to the proximal end of the cannula 102 after the cannula 102 has been advanced to the target location. The proximal end of the cannula 102 may be tapered to facilitate insertion of the applicator portion 110 into the cannula 102 and / or to allow the applicator portion 110 to be easily folded and / or rolled for insertion into the cannula 102.

[0021] In any embodiment of the device 100, the handle, cannula or outer sheath 102, inner sheath 104, or other rigid or semi-rigid components may be made from or include any suitable plastic material, metal, polyvinyl chloride, glass, acrylic, carbon fiber, and / or any combination thereof. In some embodiments, the cannula tip plug or protective tip cover may be made from a material such as plastic, metal, polyvinyl chloride, glass, acrylic, carbon fiber, rubber (such as, but not limited to, silicone). - ), and / or any combination of the above.

[0022] The distal end 106a of the applicator 106 can extend from the distal end 102a of the cannula 102. In any embodiment, the applicator 106 can have an elongated portion 108 and an applicator portion 110. The elongated portion 108 of the applicator 106 can optionally have a passageway 112 extending through the elongated portion 108 from the proximal end 108a to the distal end 108b of the elongated portion 108. The passageway 112 can be in operative fluid communication with the passageway 105 of the inner sleeve 104 at the proximal end 108a of the passageway 108. An opening or orifice 114 can be located at the distal end 108b of the body 108 and can be in fluid communication with the passageway 112. Some embodiments can have a connector 122 that couples the proximal end 108a of the body 108 to the distal end 104b of the inner sleeve 104. In this embodiment, the substance 101 can be advanced through the passage 105 of the inner sleeve 104, through the connector 122, through the passage 112 extending through the elongated portion 108 of the applicator 106, and can be exposed through the opening 114 onto the first surface 110a of the applicator portion 110 of the applicator 106.

[0023] 10 and 11, the device 300 can have an outer sleeve 302 and an applicator portion 310, and an additional movable cannula 338 having a passageway 340 disposed inside the outer sleeve or cannula 302. The passageway 340 can optionally provide a passageway for communicating or supplying the substance 101 (which can optionally be the substances described above, or in any other embodiment disclosed herein, or any other desired material) to various portions of the applicator portion 310. As described, the movable cannula 338 (also referred to herein as a fill cannula or refill cannula) can be configured to be movable relative to the outer sleeve 302, and / or at least a portion of the applicator 306, at least from a first position as shown in FIG. 10 to a second position as shown in FIG. 11. Applicator 306 and applicator portion 310 may have any of the features, materials, or other details of any of the other applicators and applicator portions disclosed herein, including, but not limited to, applicator 106 and applicator portion 110.

[0024] In any embodiment disclosed herein, the device can have an outer sleeve and applicator portion, and an additional fixed lumen or cannula (such as, for example, a fixed version of cannula 338) with a passageway inside the outer sleeve or cannula. The lumen or cannula can provide a passageway for conveying or supplying the substance 101 (which can optionally be the substances described above, or in any other embodiment disclosed herein, or any other desired material) to the applicator portion 310. For example, but not by way of limitation, the substance can be allowed to seep through an opening at the distal end of the lumen or cannula into the applicator portion. Additionally, some embodiments of the device can be configured such that the substance can be continuously injected and seeped through an opening at the distal end of the substance supply lumen or passageway such that the substance can first seep at the distal or leading edge of the applicator portion and then seep through the entire length of the applicator portion as the applicator portion is extended distally. In some embodiments, the distal end of the substance delivery lumen or cannula can be configured to exude the substance in a wide band into the applicator portion, such as with multiple openings, a manifold, or a wide slotted opening. In some embodiments, the only movable or extendable components of the device or distal end portion of the device can be the applicator and applicator portion, which may be integrally connected.

[0025] Indeed, after advancing the applicator 306 to a fully extended position, the cannula 338 can be advanced, for example, but not limited to, to a distal portion of the applicator portion 310, i.e., the first position shown in FIG. 10. The substance 101 can be advanced first through the passageway 340 onto the distal portion 310a of the applicator portion 310. The user can then continue to expel the substance into the intermediate and / or proximal portions of the applicator portion 310 as the cannula 338 is retracted (optionally slowly for better control and coverage of the applicator portion 310) toward the second position (as shown in FIG. 11). In this configuration, the user (which may optionally be a surgeon or other medical practitioner) can use the movable cannula to achieve a more uniform consistency and distribution of the substance across some or all portions (distal, intermediate, and proximal portions) of the applicator portion 310. In some embodiments, a movable cannula can allow for a more uniform consistency and distribution of material across some or all portions of the applicator portion 310 (distal portion, intermediate portion, and proximal portion) compared to a fixed passage or cannula.

[0026] Additionally, in any of the embodiments disclosed herein, the device can have a first or fixed inner cannula (such as cannula 104) and a movable cannula that surrounds the outer surface of the inner cannula 104 and can be advanced through a passageway through the distal tip as described above. In these embodiments, two passageways can be used to deliver material to the applicator portion. The movable passageway, which may optionally be an additional cannula or sleeve, can be configured to be capable of being advanced and retracted relative to the inner cannula 104, the passageway through the applicator, and / or the applicator portion.

[0027] Thereafter, the user may apply the substance 101 to a desired surface after advancing the substance 101 onto a first surface of the applicator portion 110 (or 310) of the applicator 106. For example, in applications in which the device 100 is used to apply a therapeutic substance to an ocular surface, a surgeon or medical practitioner may advance the substance 101 onto a first surface 110a of the applicator portion 110 of the applicator 106 and then use the applicator portion 110 to apply the substance 101 to a target portion of the ocular surface. In any embodiment, the applicator 106 may be fabricated or otherwise configured to be flexible and compliant to reduce the risk of puncture or other damage to the tissue to which the substance 101 is applied. In some embodiments, the applicator 106 may be fabricated from a medical grade silicone material, one or more biodegradable materials, one or more different types of alloys such as stainless steel and nitinol, or any other suitable rubber or other flexible polymeric material. In any embodiment, the applicator portion 110 can be fabricated from a material designed to increase the thermal conductivity of the applicator portion 110, i.e., a material that has high thermal conductivity properties to better enable the transfer of heat or cooling by the applicator portion 110.

[0028] Any embodiment of device 100 can optionally have a distal tip (not shown) coupled to the distal end 102a of the outer sheath or cannula 102. The distal tip can optionally have a conical or tapered profile and can be fabricated from a flexible material such as silicone or other suitable polymer, an alloy such as stainless steel or Nitinol, or the like. Alternatively, in other embodiments, the distal end 102a of cannula 102 can have a beveled or chamfered end face configured to facilitate advancement of the distal end 102a through an opening in a tissue surface or other opening.

[0029] In other embodiments, the distal end 102a may be pointed and sharp, such as a hollow needle tip, to allow insertion through tissue, such as through the sclera to access the subretinal space. Optionally, any embodiment of the device disclosed herein may have a distal tip portion distal to the cannula 102 that comprises a softer material, such as flexible silicone. The soft tip portion may be used in some applications to reduce the risk of trauma to the tissue surface. Additionally, in any embodiment, the soft tip portion may also be used to brush the surface of the tissue to gently spread or dislodge material, remove material from the tissue, etc.

[0030] Additionally, device 100 can optionally have a removable distal plug or tip cover that can be removably coupled to distal end 102b of cannula 102 and / or the distal tip of device 100. The distal plug or tip cover can provide a seal with the passageway through cannula 102 to provide a seal for maintaining sterility within the device as well as to seal the passageway through the cannula in a device pre-filled with a substance, and can be removed prior to advancing the device to the target tissue area.

[0031] Additionally, as most clearly shown in FIG. 2, some embodiments of the applicator 106 can have a curved profile in at least one of the length direction L (identified in FIG. 2) and width direction W (identified in FIG. 1). For example, without limitation, some embodiments of the applicator portion 110 can have a curved or slightly curved profile in both the length direction and width direction, the curved profile being sized and configured to resemble the curvature of the target tissue surface (which may optionally be a retinal surface or other ocular surface, such as a human eye, an animal or biological eye, etc.) and / or to better retain the desired substance on the applicator portion. In other embodiments, the applicator portion 110 can be configured to improve the ability of the applicator portion 110 to retain the substance 101 on the applicator portion 110, particularly when the applicator portion 110 is rotated, tilted, and / or turned upside down. In other embodiments, the applicator portion 110 can have a generally flat profile or shape, or any other desired profile or shape.

[0032] The cannula 102 and / or cannula (or inner sleeve) 104 of any embodiment disclosed herein can optionally have a tubular shape and a size of about 25 gauge (0.455 mm size), or 27 gauge (0.361 mm size), or 28 gauge (0.33 mm size) or less or about 28 gauge (0.33 mm size) or less to 20 gauge (0.813 mm) or more to about 20 gauge (0.813 mm) or more, or 27 gauge (0.361 mm size) to 24 gauge (0.511 mm) or about 24 gauge (0.511 mm), or any value within these ranges, or from any value to any value within these ranges. Optionally, in other embodiments, larger or smaller cannulas can be used for the inner and / or outer cannula or sleeve.

[0033] In any embodiment, the cannula, cannula base, cannula body, and / or cannula tip can have a cross-sectional diameter of 0.1-0.5 mm, 0.5-1 mm, 1-2 mm, 2-3 mm, 3-4 mm, 4-5 mm, 5-6 mm, 6-7 mm, 7-8 mm, 8-9 mm, or 9-10 mm. Optionally, the cannula, cannula base, cannula body, cannula tip, and / or cannula exit port can have a length of 0.1-0.5 mm, 0.5-1 mm, 1-2 mm, 2-3 mm, 3-4 mm, 4-5 mm, 5-6 mm, 6-7 mm, 7-8 mm, 8-9 mm, 9-10 mm, 10-20 mm, 20-30 mm, 30-40 mm, or 40-50 mm. Additionally, the cannula, cannula base, cannula body, cannula tip, and / or cannula exit port can have an outer diameter, inner diameter, and a width between the inner and outer diameters of 0.01-0.05 mm, 0.05-0.1 mm, 0.1-0.5 mm, 0.5-1 mm, 1-2 mm, 2-3 mm, 3-4 mm, 4-5 mm, 5-6 mm, 6-7 mm, 7-8 mm, 8-9 mm, 9-10 mm, 10-20 mm, 20-30 mm, 30-40 mm, or 40-50 mm.

[0034] For other non-ophthalmic applications, the cannula 102 can optionally have a tubular shape and a cross-sectional size or inner diameter from at or about 10 mm to at or about 200 mm or more, or from at or about 40 mm to at or about 80 mm.

[0035] Some embodiments of the devices and methods disclosed herein can be configured to deliver and apply a variety of materials or substances of various viscosities to a target tissue or surface. Examples of substances that can be used with any of the devices, systems, and methods disclosed herein include, but are not limited to, adhesives, bioadhesives, gels, hydrogels, thick liquid or semi-liquid processing substances, bilayer hydrogels, non-solids, polyethylene glycol solutions, trilysine amine solutions, polymer hydrogels, thermoresponsive gels, and any combinations of the above. Examples of bioadhesive substances that can be used with any of the embodiments disclosed herein include, but are not limited to, ReSure™ sealant, polyethylene glycol hydrogels and other hydrogels, cyanoacrylates, fibrin glues, polyethylene glycol solutions, trilysine amine solutions, glycoproteins, elastic proteins, carbohydrates, mucopolysaccharides, and the like. In some embodiments of the system or device, the bioadhesive material comprises a resin. Additionally, UV or light activated bioadhesives can optionally be used with any of the device embodiments disclosed herein. In some such embodiments, the system, kit, or device can include a light or optical fiber for activating the bioadhesive material.

[0036] Additionally, a temperature-activated bioadhesive can optionally be used with any of the device embodiments disclosed herein, in some such embodiments, the system, kit, or device can include a material that directs heat to activate the bioadhesive.

[0037] In some embodiments, the substance may include an adhesive or a bioadhesive. As used herein, the term "adhesive" shall be given its ordinary meaning and is intended to include bioadhesives. Examples of adhesives that may be used in any embodiment disclosed herein include, but are not limited to, polyvinyl acetate, glue, aliphatic, cyanoacrylate, epoxy, polyurethane adhesives, and contact cements. Examples of bioadhesives include, but are not limited to, polyvinyl acetate, glue, aliphatic, cyanoacrylate, epoxy, polyurethane adhesives, and contact cements. In some embodiments, the adhesive is a biomimetic material. In some embodiments, the adhesive is not a bioadhesive.

[0038] Additionally, any embodiment disclosed herein can also be configured to use one or more substances that polymerize when the temperature of the substance reaches a threshold or range of values, such as, for example, but not limited to, normal body temperature or a temperature of at or about 80° F. to at or about 100° F. or above, 90° F. to at or about 90° F. to at or about 100° F. or above, 95° F. to at or about 95° F. to at or about 100° F. or above, or any value to any value within these ranges. Additionally, any of the embodiments may be used to apply a low temperature cure material to the tissue surface, i.e., a material that polymerizes when the temperature of the material drops to a threshold or range of values ​​such as, for example, but not limited to, 10° F below body temperature, or any value from at or about 70° F. or below to at or about 90° F., or from 80° F. or about 80° F. to 90° F. or about 90° F., or any value to any value within these ranges.

[0039] Additionally, any of the embodiments disclosed herein can be configured to use one or more substances that polymerize or are activated by light of any number of different wavelengths. The activation light can be provided by a special applicator within the material delivery device or separate from the material delivery device. Suitable substances that can be used can include substances that are typically used or approved for use in the subretinal space, vitreous cavity, or ocular surface, including the conjunctiva or subconjunctiva, as well as substances that can be used to close gaps in tissue.

[0040] In any embodiment, the applicator portion 110 may be biased to be sufficiently flexible or otherwise structurally biased to be collapsible in the width direction W while being capable of being retracted into the outer sleeve 102 to minimize the forces and resultant trauma that may occur in more rigid materials. Figures 3 and 4 show side and end views, respectively, of the embodiment of the device 100 shown in Figure 1, illustrating the device in a first or retracted state in which the applicator portion 110 is housed or retracted within the outer sleeve 102. Figure 5 shows an end view of another embodiment of the device 100 and applicator portion 110.

[0041] The inner sleeve 104 and applicator 106 may optionally be advanceable and retractable through a lumen or passageway 103 of the outer sleeve 102, for example between a first state shown in Figures 3 and 4 and a second or deployed state shown in Figures 1 and 2.

[0042] When the applicator 106 is in the first or retracted state, the distal portion of the device 100 can have a smaller profile or cross-sectional size that can be defined by the outer sleeve 102 such that the distal portion of the device 100 can be advanced through an opening in a tissue surface requiring less force and therefore less risk of trauma to the tissue. Some embodiments of the device 100 can be configured such that when the applicator portion 110 is retracted or located within the outer sleeve 102, the applicator portion 110 can assume a curved or helical shape to fit snugly within the inner space of the outer sleeve, thereby forming a space 130 enclosed by the first surface 110a of the applicator portion 110, as best shown in Figures 4 and 5.

[0043] 5, the applicator portion 110 can be biased or otherwise configured such that when the inner sleeve 104 and the applicator 106 are all retracted into the outer sleeve 102 from the second state to the first or retracted state, the applicator portion 110 collapses into a more compact or narrow shape or state as described above or illustrated in FIG. 5, such that the device 100 can be retracted through the tissue opening with the applicator 106 retracted into the outer sleeve 102. As illustrated and described, the applicator portion 110 can have a width W that is greater than the width of the outer sleeve 102. Because the applicator portion 110 is configured or biased to transition to a more compact profile, retracting the applicator portion 110 into the outer sleeve 102 as shown in FIGS. 4 and 5 can reduce the size of the distal portion of the device 100 to the size of the outer sleeve 102. This can reduce trauma to the tissue when the device 100 is retracted through the tissue opening (if present). In any embodiment, applicator portion 110 can be configured with any features or made of any material that allows it to be folded, rolled, compressed, squeezed, narrowed, or otherwise reduced in width W or size to fit within an outer sleeve.

[0044] The applicator portion 110 can have or define a first width when the applicator portion 110 is in a first position (the applicator portion 110 is housed within the outer sleeve 102) and a second width when the applicator portion 110 is in a second position (the applicator tip extends past the opening in the distal end 102a of the outer sleeve 102). The second width of the applicator portion 110 can be substantially greater than the first width of the applicator portion 110. In any embodiment disclosed herein, the second width of the applicator portion 110 can be about 5 times as large as the first width of the applicator portion 110, or from 2 times or about 2 times (or, optionally, less) to 8 times or about 8 times (or, optionally, more) as large as the first width of the applicator portion 110, or from 3 times or about 3 times to 6 times or about 6 times as large as the first width of the applicator portion 110.

[0045] In any embodiment disclosed herein, the second width of the applicator portion 110 may be 2 mm, or about 2 mm, or 3 mm, or about 3 mm, or 4 mm, or about 4 mm, or 1.5 mm or about 1.5 mm (or smaller) to 6 mm or about 6 mm (or larger), or 2 mm or about 2 mm to 4 mm or about 4 mm, or 2 mm or about 2 mm to 3 mm or about 3 mm, or any size within these ranges, or from any size to any size within these ranges. In other embodiments where the device can be used on tissues other than the eye, the second width may be any value, or from any value to any value, that is two times greater than the values ​​or ranges recited above, or three times greater than the values ​​or ranges recited above.

[0046] Applicator portion 110 can be made of a solid, non-fenestrated material. Or, alternatively, applicator portion 110 can be made of a fenestrated material with multiple openings or slits, such as a sieve or flyswatter, or any combination thereof. The openings or slits can optionally be of various sizes and / or dimensions.

[0047] A further advantage of retracting the applicator portion 110 into the sleeve 102 is that as the substance 101 advances through the passageway formed in the inner sleeve 104 and the applicator 106, the substance 101 can contact and substantially cover the first surface 110a of the applicator portion 110 by filling the space 130. In this embodiment, to improve coverage of the first surface 110a of the applicator portion 110 by the substance 101, a user can retract the applicator portion 110 into the outer sleeve to form a circular or rolled shape of the applicator portion 110 to form the space 130 through which the substance 101 can advance and, optionally, substantially fill.

[0048] In any embodiment, the applicator portion 110 can be retracted into the sleeve 102 in an initial state of the device 100. The substance 101 can optionally be pre-provided in the passages 105, 112 and in the volume 130 before advancing the device 100 to the target location. In addition, the substance can optionally be stored in the passages 105, 112 and in the volume 130 before using the device. In such an embodiment, a thermally responsive gel or other thermally activated substance can be used to extend the shelf life of the pre-filled device and reduce the likelihood of the substance hardening during storage of the device or before application of the device. Heat from the patient's body or an additional heat source (such as, but not limited to, a heat source integrated into or applied to the applicator portion 110) can be used to activate the thermally responsive substance. In other embodiments, a user or surgeon can bring substance 101 through passages 105, 112 after device 100 has been advanced to the target location and / or after applicator portion 100 has been advanced to the second state or position or the deployed state or position (shown in FIG. 1).

[0049] The device 100 can be optionally configured to allow the applicator 106 to be selectively connectable to the inner sleeve 104 at the connection 122. In this configuration, the device 100 can enable a number of additional functions that would not be possible without the connectable interface 122. As a first example, if a desired procedure is Executed substance 101 butAfter application to the target surface, a user of the device can disconnect the applicator 106 from the inner sleeve 104 at the connector 122, and thus retract the outer sleeve 102 and inner sleeve 104 from the target location without retracting the applicator 106 or a portion of the applicator 106, such as the applicator portion 110. In some applications, such as ophthalmic applications, for example, it may be desirable to leave the applicator 106 in contact with the ocular tissue until a desired level of healing is achieved, or indefinitely. Thereafter, the distal tip 106, or a portion thereof, may be left at the target location or removed from the target location by any suitable means, such as by reconnecting the applicator 106 to the inner sleeve 104 and retracting the applicator 106 inside the outer sleeve 102. The distal tip 106 can be fabricated from a bioabsorbable material, an inert material, or the like. If inert and left at the target location, the applicator portion 110 can provide additional scaffolding or support to tissue even after the material has dissolved or dissipated.

[0050] In any embodiment, any portion of the device 100, including but not limited to the passageway 105 of the inner sleeve 104, can be pre-filled with the substance 101 and stored in this partially filled state. The applicator 106 can be provided in an unattached or detached state, where the applicator 106 is detached from the inner sleeve 104 and does not have any substance 101. In this configuration, after coupling the applicator 106 to the inner sleeve 104 at the connector 122, a user can advance the substance 101 through the passageway 112 of the elongated portion 108 of the application tip 106 and from the opening 114 to the applicator portion 110 when the applicator portion 110 is in either the first state or the second state.

[0051] The connector 122 in any embodiment disclosed herein may be configured to seal the passageway 105 of the inner sleeve 104 when the applicator 106 is disconnected from the inner sleeve 104, thereby preventing passage of the inner sleeve 104 through the connector 122. Road 1 05 may be configured to be self-sealing so as to prevent the escape of materials within the 05.

[0052] Any embodiment of applicator portion 110 can optionally be configured to be less flexible in the length direction (designated L in FIG. 2) than in the width direction W. The material of applicator portion 110 can be configured to have reinforcing features or materials, such as, but not limited to, corrugations, reinforcing wires, wire loops, ribs, sheets, or other structural members, longitudinal channels, ribs, or other features made from Nitinol, stainless steel, or other alloys, to increase the stiffness of applicator portion 110 in the length direction and decrease the stiffness of applicator portion 110 in the width direction.

[0053] Additionally, some embodiments can be optionally configured to deliver or apply a flexible film of a substance to a surface or to deliver any substance or material to a confined space, such as the eye, through a small opening in the eye.

[0054] 6 shows a top view of another embodiment of an applicator tip 156 that can be used with any of the embodiments of the device disclosed herein, such as, but not limited to, any of the above-disclosed devices 100. Applicator tip 156 can include any feature, material, or other detail of any of the other applicator tip embodiments disclosed herein, such as, but not limited to, applicator 106 described above, in combination with or in place of any of the features described below to form new embodiments.

[0055] 6, the applicator portion 160 can include a plurality of openings 163 in fluid communication with the passageway 162 extending through the elongated portion 158. The plurality of openings 163 can be formed in any desired pattern and in any desired number about the first surface 160a of the applicator portion 160. For example, without limitation, about 20 openings 163, 5 or about 5 to 40 or about 40 openings, 10 or about 10 to 30 or about 30 openings, 15 or about 15 to 25 or about 25 openings, any number of openings 163 within these ranges, or any number to any number within these ranges, may be formed in the applicator portion 160.

[0056] Openings 163 may provide or allow for a more uniform distribution of substance 101 on first surface 160a of applicator portion 160. Additionally, because openings 163 extend only through first surface 160a of applicator portion 160 to passageway 162, openings 163 may increase the flexibility of applicator portion 160 and / or facilitate collapsing thereof such that applicator portion 160 may be easily folded, bent, and / or retracted into the outer sleeve of the device when the device is in the first or retracted state.

[0057] 7A illustrates a cross-sectional view of another embodiment of device 200 for applying substance 101 to a surface of an object, showing device 200 in a second or deployed state. Device 200 can include any feature, material, or other detail of any of the other device embodiments disclosed herein, such as, but not limited to, device 100 described above, in combination with or in place of any of the features described below.

[0058] In some embodiments, the device 200 can include a cannula or outer sleeve 202 (also referred to herein as an elongate body) having a lumen or passageway 203 therein through which the substance 101 can be advanced, and an applicator tip 206 coupled to an inner core 204. The applicator tip 206 and inner core 204 can be movable (e.g., extendable and retractable) within the outer sleeve 202. In some embodiments, the applicator tip 206 and inner core 204 can be rotatable within the outer sleeve 202. The outer sleeve 202 can be configured to provide additional rigidity and maneuverability to the applicator tip 206 as well as to advance the substance through the device 200 and into the applicator portion 210 of the applicator tip 206 to facilitate or improve a user's control of the device 200 during application of the substance 101.

[0059] The distal end 206a of the applicator tip 206 can extend from the distal end 202a of the cannula or outer sleeve 202. In any embodiment, the applicator tip 206 can have an elongated portion 208 and an applicator portion 210. A seal 222 can optionally be disposed at the distal end 202a of the outer sleeve 202 of the device 200 to seal around the outer surface of the elongated body 208 except for a channel or passage aligned with a first surface 210a (which can be referred to as an applicator surface) of the applicator portion 210. Additionally, as with any embodiment disclosed herein, fluoroscopic or radiopaque markers can be disposed along the outer sheath 202, such as at the distal end 202a of the outer sheath 202, and / or along the applicator tip 206 to provide the surgeon with visualization of the location of these components.

[0060] In this embodiment, as shown in FIGURE 7A, the substance 101 can travel through the space between the outer surface of the elongate body 208 inside the outer sleeve 202 and the inner surface of the outer sleeve 202, so there is no need to form a separate lumen through the elongate body 208 and the applicator tip 206. In some embodiments, a channel or space can be formed along the length of the outer surface of the inner core 204 or the inner surface of the outer sleeve 202, along or through which the substance 101 can be advanced. In other embodiments, as shown in FIGURE 7B, the outer sleeve 202 can have a separate lumen 203 through which the substance 101 can be advanced.

[0061] In some embodiments, the elongate body 208 may extend from at least the proximal end of the outer sleeve 202 to the applicator portion 210 such that a separate inner core is not necessary. In some embodiments, the elongate body 208 or the proximal end of the inner core 204 may extend through or through a handle (optionally with a suitable seal as needed) such that a user can manipulate the elongate body 208 to advance and retract the applicator portion 210 as needed. Similar to the applicator portion 110 described above, the applicator portion 210 may be configured to be retractable within the outer sleeve 202 and may be configured to be movable between a first or closed state and a second or extended state. For example, and not by way of limitation, the substance 101 can be applied to the distal portion 206a of the applicator tip 206 by retracting the applicator tip 206 into the outer sleeve 202 and then extending it as the substance 101 is advanced past the distal end 202a of the outer sleeve 202, and can be applied along the length of the applicator tip 206 as the applicator tip 206 is advanced distally relative to the distal end 202a of the outer sleeve 202.

[0062] In any embodiment of device 200, the handle, cannula or outer sheath 202, inner sheath 204, or other rigid or semi-rigid components may be made from or include any suitable plastic material, metal, polyvinyl chloride, glass, acrylic, carbon fiber, and / or any combination thereof. In some embodiments, the cannula tip plug or protective tip cover may be made from a material such as plastic, metal, polyvinyl chloride, glass, acrylic, carbon fiber, rubber (such as, but not limited to, silicone). - ), and / or any combination of the above.

[0063] Any of the embodiments disclosed herein can have a handle (not shown) at the proximal end of the device 100. The handle can have any detail of any current or existing design of biomaterial or other liquid material delivery devices. In some embodiments, the handle can have a first handle portion or member that can be coupled to the outer sleeve 102 of the device 100. An additional or second handle can be coupled to the inner sleeve 104. The second handle member can be independently movable relative to the first handle member such that a user can advance and retract the inner sleeve 104, and thus the applicator 106 when coupled to the inner sleeve 104, relative to the outer sleeve 102.

[0064] A delivery device or delivery means (not shown) for providing the substance 101 in the passageway 105 can be in fluid communication with the proximal end 104b of the inner sleeve 104. The delivery device can be coupled to or part of the handle of the device 100. In some embodiments, the delivery device can include a plunger or syringe, a fillable chamber that can be filled or accommodated with the substance, a compressible valve, a compressible bladder, or other device configured to expel the substance 101 through the passageway 105. Additional mechanisms for advancing the substance 101 into the inner sleeve 104 can include mechanical pumps, powered pumps, pneumatic pumps or cylinders, electromechanical pumping means, and the like. Optionally, the handle can include a port configured to receive an adhesive material within the handle. A bladder or other expulsion device of the material as described herein can be fluidly coupled to the port.

[0065] FIG. 8A shows an example of a system and / or device including a plunger 41, a handle 35, a cavity 40 for holding a bioadhesive material, an extension knob 36, a rod 38, a locking connector 39, and a flexible loop 37 that houses a film 37 of bioadhesive material (partially extended). The plunger 41 can be used to expel the bioadhesive material through the hollow cannula and / or into the flexible loop 37 when pressed by a user (e.g., using pressure from the user's finger or air pressure provided by an external device connected to the handle). In some embodiments, the plunger 41 is incorporated into the examples of FIG. 8B and / or FIG. 8C. For example, the extension knob 36 can be used to extend the flexible loop 37 from a retracted position as seen in FIG. 8B. In some embodiments, the flexible loop 37 can be replaced with any of the applicator tips disclosed elsewhere herein.

[0066] Figure 8B shows an example of a system and / or device that includes an extension knob 36, a rod 38, a flexible loop 37 that houses a film of bioadhesive material, and two guide ridges 42. Some embodiments include a retractable loop like that of Figure 8B that unfolds as shown in Figure 8A and / or Figure 15C.

[0067] 8C shows an example of a system and / or device that includes a handle 47, a rod 38, a cannula 48, and a flexible loop 37 that houses a film of bioadhesive material. The cannula may be removable or non-removable.

[0068] Any component of the device 100 in any embodiment disclosed herein, including, but not limited to, the handle portion, the outer sleeve 102, the inner sleeve 104, and / or the distal tip 106, can be configured to have temperature regulating capabilities. In some embodiments, the outer sleeve 102, the inner sleeve 104, and / or the distal tip 106 can be optionally configured to dissipate heat from the device, which may result from heat generated by the substance 101 as it advances through the device 100. For example, one or more of the outer sleeve 102, the inner sleeve 104, and the distal tip 106 can optionally be fabricated from a material such as a thermally conductive metal (e.g., copper, steel, Nitinol, aluminum, or other alloys, etc.) or can include other materials that have good or high thermal conductivity that can conduct heat away from certain portions of the device 100. In some embodiments, the outer sleeve 102 and / or the inner sleeve 104 can be optionally configured to conduct or dissipate heat, but the applicator 106 is not configured to dissipate or conduct heat.

[0069] Alternatively, the outer sleeve 102, the inner sleeve 104, and / or the distal tip 106 can optionally be configured to retain heat in one or more components of the device that may result from heat generated by the substance 101 as it advances through the device 100. For example, one or more of the outer sleeve 102, the inner sleeve 104, and the distal tip 106 can optionally be fabricated from a material with good or high insulating capabilities that can reduce the amount of heat conducted away from a particular portion of the device 100. In some embodiments, the outer sleeve 102 and / or the inner sleeve 104 can optionally be configured to retain heat, while the applicator 106 is not configured to retain heat.

[0070] In some embodiments, one or more of the components of device 100 (which may include outer sleeve 102 and inner sleeve 104, or optionally may include outer sleeve 102, inner sleeve 104, and applicator 106) may be pre-cooled to a desired temperature below room temperature or body temperature such that if substance 101 generates any heat, the temperature of device 100 does not rise above a desired temperature threshold, which may optionally be the patient's body temperature.

[0071] Further, in some embodiments, one or more of the components of the device 100 (which may include the outer sleeve 102 and the inner sleeve 104, or may optionally include the outer sleeve 102, the inner sleeve 104, and the applicator 106) may be configured to maintain the substance 101 (which may be a hydrogel) at a temperature below a threshold temperature value such that the substance 101 is less adhesive or adhesive when contained within the device. When the substance 101 is advanced to the applicator portion 110 or applied to a target tissue or surface, the temperature, and therefore the adhesiveness, of the substance may be increased. For example, but not limited to, the outer sleeve 102 may be sized and configured such that the inner diameter of the passageway 103 is larger than the outer surface of the inner sleeve 104 such that a space is created between the inner surface of the outer sleeve 102 and the outer surface of the inner sleeve 104. A cooling fluid may be directed through the individual lumens or otherwise through the passageway 103 to provide a cooling source to the inner sleeve 104 and thus the substance 101. One or more seals can be used to seal the ends of the outer sleeve 102 to the inner sleeve 104 so that the cooling fluid does not leak from the device 101. Alternatively, an outer shell configured to surround the outer sleeve 102 can be disposed around the entirety of the outer sleeve 102 to provide additional cavities or passages for conducting cooling fluid to reduce the temperature within the outer sleeve 102 and, therefore, the temperature of the substance 101. Inlet and outlet ports can be formed in or coupled to the handle for inlet and outlet of the cooling fluid through the device 100. The cooling fluid can optionally include ammonium nitrate.

[0072] Optionally, a rheostat and / or other means can be located in the handle and used to control the temperature of any or all of the components of the device 100. Optionally, one or more heat or other sensors can be used to monitor the temperature of any or all of the components of the device 100. Additionally, any of the embodiments of the device 100 disclosed herein can be configured with the ability to automatically maintain the temperature of each portion of the device within a specified range, even if a substance or application may have a tendency to increase the temperature of the device or its components.

[0073] Additionally, any embodiment of the device 100 disclosed herein can be configured to transfer heat to one or more of the components of the device 100 (which may include the outer sleeve 102 and the inner sleeve 104, or may optionally include the outer sleeve 102, the inner sleeve 104, and the applicator 106, or may optionally include only the applicator 106 or the applicator portion 110) to increase the temperature of the substance 101 contained within the device and / or at the applicator tip for transferring or delivering heat to a target tissue. In some embodiments, a thermally conductive material, such as, but not limited to, copper, steel, nitinol, aluminum, or other alloys, can be integrated into the device and extend lengthwise along the device to transfer heat from a heat source adjacent the proximal end or handle of the device to the applicator 106. Optionally, one or more thermoelectric components or means may be used to transfer heat to one or more of the components of device 100 (which may include outer sleeve 102 and inner sleeve 104, or which may optionally include outer sleeve 102, inner sleeve 104, and applicator 106, or which may optionally include only applicator 106 or applicator portion 110).

[0074] In any embodiment disclosed herein, the device or method may include removing or liquefying solidified substances or gels from the device 100 or tissue surface (such as tissue on the surface of the eye) by increasing or decreasing the temperature of the inner sleeve 104, applicator 106, or applicator portion 110, if desired, depending on the particular thermal response characteristics of the material. The liquefied substances or gels can then be aspirated through the device and removed through the proximal end of the device or handle portion. The device may optionally be configured with one or more suction tubes or channels for aspirating any liquefied substances or gels or any other substances desired to be removed from the device. The tubes may optionally be heated or temperature controlled to ensure that the removed substances remain in a liquid state.

[0075] Any of the embodiments of the devices disclosed herein can include an internal cauterization component. Such an embodiment can include a cannula with a fiber or wire for light or cauterization. FIG. 9 shows an example of a cannula with a fiber or wire for light or cauterization. This example includes an optical fiber 65 within a tube along the edge of the cannula. The optical fiber 65 includes a beveled end 62 in this example, but in some embodiments, the end of the optical fiber 65 is straight. If the end 62 of the optical fiber 65 is beveled, it may be beveled at an angle that matches the angle of the bevel at the tip of the cannula. This example includes illumination 60 emitted by the end 62 of the optical fiber 65.

[0076] In some embodiments, the cannula tip can be configured to be used for cauterization. For example, an additional tube can be provided configured to pass additional material (such as a liquid) that can emerge from the cannula tip as a spray or droplets. For example, the additional material can be used to activate the bioadhesive material. In some embodiments, the device or system, or components thereof, such as the handle, cannula, cannula tip, light, or optical fiber, can be configured to emit light at a wavelength that activates, concentrates, or cures the bioadhesive material.

[0077] The system and / or device can be operated in a manner that increases the temperature of the cannula tip (e.g., using an internal cauterization component). This is advantageous in some embodiments to aid in the release of the bioadhesive from the applicator portion if the bioadhesive material is a temperature responsive material that becomes more flowable at higher temperatures. Some embodiments include a cryotherapy component, such as a cryotherapy handpiece. In some embodiments, the system or device can be operated in a manner that decreases the temperature of the applicator tip (e.g., using a cryotherapy component). This is advantageous in some embodiments to aid in the release of the bioadhesive from the applicator portion if the bioadhesive material is a temperature responsive material that becomes more flowable, brittle, or releasable at lower temperatures.

[0078] The substances used with any of the embodiments disclosed herein may include heat-activated substances. Additionally, the device may be configured to provide a source of warm or cold air to the substance, optionally through an additional lumen in the inner cannula 104, through an additional lumen or passage outside the inner cannula 104, through an entirely separate cannula from a separate device, or otherwise. The warm or cold air may be blown onto the applied substance. The device may optionally include a filter to filter the air before warming or cooling it and applying it to the substance. In any embodiment, the passage of the air source may have any of the sizes disclosed herein for the outer cannula 102 and / or inner cannula 104. The source of warm or cold air may be a separate device, may be integrated into the outer or inner cannula, or may be integrated into other surgical devices, such as a vitreous surgery machine, configured to filter and deliver air to the eye or other instruments.

[0079] Any embodiment of the device disclosed herein may be incorporated or included in a kit or system that also includes one or more substances, which may be any of the substances disclosed herein or other substances now known or later developed. The kit may further include a material dispenser for providing the substance if not included in the device. The kit may optionally further include a tip plug or protective cover for the distal end of the device if not already included in the device. The system, device, or kit may be sterile or may be pre-sterilized. In some embodiments, the kit includes a pre-sterilized material dispenser as described herein.

[0080] The kit or system can further include any of the other components or devices disclosed herein, such as, for example, but not limited to, one or more of a hardening component and a device for applying the hardening component to the substance after the substance has been applied to the target tissue surface. Additionally, in any of the embodiments disclosed herein, the substance or one or more different substances can be provided in a capsule or self-contained syringe that can be coupled to an opening, port, or the like in a handle portion of the device.

[0081] Some embodiments relate to the use of a system, device, or kit for applying a substance (which may include any of the substances listed above, such as bioadhesives) to the eye or retina for purposes such as treating the eye, including the retina, sclera, conjunctiva, and cornea. In any such method, a cannula can optionally be advanced into the eye using any known or commonly used technique. The surgical procedures disclosed herein can include puncturing the surface of the eye or other tissue of the eye, or can include treating eye tissue without entering or puncturing any eye tissue.

[0082] The methods disclosed herein can include advancing a substance into an applicator portion of the applicator tip and from the applicator portion to a target tissue, which can be ocular tissue or optionally retinal tissue. Any of the embodiments disclosed herein can optionally be used for repair of retinal tears or other defects or tissues within the body, as well as other surgical applications beyond those disclosed herein, as disclosed elsewhere herein. Some embodiments can include the operation of a button, other manual control, or foot pedal on a handpiece of a device or system to control a valve, for example, to control the aspiration of a substance, the injection of a substance, or the injection or delivery of an activating solution or other sclerosing means, to allow a substance to flow through a passageway of the handpiece and / or a flow path of the device, etc.

[0083] Any of the embodiments disclosed herein can include a means for curing the material after it has been applied to the target surface, including a light emitting facility, a UV light emitting facility, application of elevated temperature (e.g., application of heat), application of lower temperature (e.g., application of cooling), and the like.

[0084] Additionally, any of the embodiments disclosed herein may be configured for use in non-ocular tissue, such as, but not limited to, applications in gastrointestinal tissue, colonic tissue, and the like.

[0085] In some embodiments, the material delivered by the device may be delivered transvitreally. For transvitreous use, the device delivery can use a cutting action to remove cohesive / adhesive material after delivery. In some embodiments, excess can be removed by a vitreous cutter and / or suction. Transvitreous delivery can be utilized in air-filled eyes to avoid floating adhesive material to non-target ocular structures such as the lens / IOL / ciliary processes / angle, corneal endothelium, etc., which may obscure vision through the lens / IOL or impair aqueous inflow / outflow.

[0086] During application of the substance, one or more portions of tissue can be covered with fluid to protect or mask such tissue and avoid contact with the substance. Additionally, air can be used to control the application of the substance and / or to avoid contact of some tissue surfaces with the substance. For example, but not limited to, an air disk can be generated to cover or protect the tissue surface, adhesive material can be precipitated on the fluid surface rather than on the underlying structure, and / or can be activated (made non-sticky) immediately to avoid adhesion to non-target tissue. Activation in any embodiment disclosed herein can include activation with water or similar liquid. If the substance is heat-responsive, any undesirable material can have its temperature adjusted by any embodiment of the device, and the material can be converted to a liquid form, after which such material can be aspirated from the eye.

[0087] Transscleral delivery is contemplated and may include delivery of material through the subretinal space to a retinal break. After the material adheres to the retina after delivery through the tapered end of the device or needle, the material may be severed as the needle is withdrawn from the sclera. The material may act as a buffer to prevent incarceration of the retina into the scleral defect left by the cannula, needle, or device utilized to traverse the scleral and choroidal tissues.

[0088] The delivery device may be single, double, or triple bore. In some embodiments, a double bore device includes one bore for delivery of material and a second bore for refluxing intraocular fluids outside the eye when IOP is elevated. In some embodiments, one of the bores includes an optical fiber that can be used for illumination. In some embodiments, one of the bores includes a fiber that delivers laser light. In some embodiments, one of the bores includes a fiber that delivers heat or some other energy source used to cure the injected material.

[0089] In some embodiments, the triple bore device includes one bore for delivery of material, one bore for the passage of gas used to create a bubble or film of adhesive material, and a third bore for refluxing intraocular fluids outside the eye when the IOP is elevated.

[0090] 12-17 illustrate one optional method of using an embodiment of the device 300. With reference to FIG. 12, a cannula 302 can be advanced into the eye. As shown in FIG. 12, an applicator portion 310 can be positioned within the cannula 302 as the cannula is advanced into the eye, or can be retracted into the cannula 302. In some embodiments, the applicator portion 310 can have a substance thereon when the applicator portion is positioned within the cannula 302. In some embodiments, a substance can be applied to the applicator portion 310 after the applicator portion 310 is advanced distally past the distal end of the cannula 302, as described below. Thereafter, the applicator portion 310 can be extended from the distal end of the cannula 302 and allowed to expand to a second or expanded state, as shown in FIG. A cannula 338 (also referred to herein as a delivery cannula) may be extended through the outer cannula 302. FIG. 14 shows the cannula 338 extended such that its distal end is generally aligned with the distal end of the outer cannula 302. The cannula 338 may be extended past the distal end of the outer cannula 302 toward the distal end 310a of the applicator portion 310 of the applicator tip, as shown in FIG. 15. The substance 101 may then be advanced through a passageway 340 of the cannula 338 and expelled onto the applicator portion 101, as shown in FIG. 16. The outer cannula 302 and applicator portion 310 may then be moved and manipulated by a user to apply the substance 101 to the target tissue, as shown in FIG. 17.

[0091] Some embodiments of the system and / or device further include an internal material supply chamber in the handpiece or in the cannula for cooling or heating fluid or other fluids or gases that can be used with device 100. The internal material supply chamber can optionally include an elongated body with a proximal end and a distal end that includes a material supply tip and / or an exit port. The internal material supply chamber can optionally be within or adjacent to at least a portion of passageway 105.

[0092] In some embodiments of the systems and / or devices, the internal material supply chamber, the elongate body of the internal material supply chamber, the material supply tip, and / or the material supply exit port have a cross-sectional diameter of 0.1-0.5 mm, 0.5-1 mm, 1-2 mm, 2-3 mm, 3-4 mm, 4-5 mm, 5-6 mm, 6-7 mm, 7-8 mm, 8-9 mm, 9-10 mm, 10-20 mm, 20-30 mm, 30-40 mm, or 40-50 mm. In some embodiments of the system or device, the internal material supply chamber, the elongate body of the internal material supply chamber, the material supply tip, and / or the material supply exit port have a length of 0.1-0.5 mm, 0.5-1 mm, 1-2 mm, 2-3 mm, 3-4 mm, 4-5 mm, 5-6 mm, 6-7 mm, 7-8 mm, 8-9 mm, 9-10 mm, 10-20 mm, 20-30 mm, 30-40 mm, 40-50 mm, 50-60 mm, 60-70 mm, 70-80 mm, 80-90 mm, 90-100 mm, 100-150 mm, or 150-200 mm.

[0093] Some embodiments of the system and / or device further comprise a second internal material supply chamber. In some embodiments of the system or device, the internal material supply chamber and the second internal material supply chamber each contain a separate bioadhesive material, such as a polyethylene glycol solution and a trilysine amine solution, a hydrogel, a bilayer hydrogel, or a polymeric hydrogel.

[0094] FIG. 18A is a perspective view of the end of an embodiment of a cannula 402 that can be used with any embodiment of the device disclosed herein. FIG. 18B is a cross-sectional view taken through line 18B-18B of FIG. 18A of the embodiment of the cannula 402 shown in FIG. 18A. FIG. 18C is a top view of the embodiment of the cannula 402 shown in FIG. 18A. As shown, the cannula 402 can have a notch or cutout 404 formed at the end of the cannula 402, which can aid in retracting or reducing in size (e.g., pinching or folding) for any embodiment of the applicator portion disclosed herein as the applicator portion is retracted into the distal end of the outer sleeve or cannula. With reference to FIG. 18C, in some embodiments, the cutout 404 can have an asymmetric shape, for example, but not limited to, about a plane that extends through the axial centerline C of the cannula 402, through a plane that is perpendicular to the plane of the figure (e.g., perpendicular to the plane of the paper). In some embodiments, the notch 404 can terminate in a curved end 406. In other embodiments, the notch 404 can have a triangular shape with one side of the notch parallel to the axial centerline of the cannula. In other embodiments, the notch can have a triangular shape with both sides of the notch tapered or angled or otherwise "v" shaped, such as notch 424 of cannula 422 shown in FIGS. 20A and 20B. In some embodiments, the apex or proximal end portion 424a of the v-shaped notch can be rounded or have a radius, as shown in FIG. 20B. In other embodiments, the notch can have rounded ends and parallel sides, as in FIG. 20C, or can otherwise have a generally "u" shape.

[0095] 18C , a notch in any embodiment disclosed herein (such as, but not limited to, notches 404, 414, and 424) can have a length L and a width W adjacent the end of cannula 402, and the cannula embodiments disclosed herein can have a diameter D. For example, but not limited to, the width W of a notch (or width W1 of notch 414) can be 30% (or about 30%) of the cannula diameter D, or from 20% (or about 20%, or less than 20%) to 100% (or about 100%, or more than 100%) of the cannula diameter D, or from 30% (or about 30%) to 50% (or about 50%) of the cannula diameter D, or any value or from any value to any value within these ranges. In some embodiments, the width W of the notch (or the width W1 of the notch 414) may be 0.25 mm (or about 0.25 mm), or 0.1 mm (or, in some embodiments, about 0.1 mm or less) to 1.5 mm (or, in some embodiments, about 1.5 mm or more), or 0.25 mm (or, in some embodiments, about 0.25 mm) to 0.75 mm (or, in some embodiments, about 0.75 mm), or any value within these ranges, or from any value to any value.

[0096] In any embodiment, the length L of the notch of any embodiment disclosed herein may be about 30% of the length of the applicator portion, or from 20% (or about 20% or less than 20%) to 100% (or about 100% or more) of the length of the applicator portion, or from 30% (or about 30%) to 60% (or about 60%) of the length of the applicator portion, or from 30% (or about 30%) to 50% (or about 50%) of the length of the applicator portion, or any value or from any value to any value within these ranges. In some embodiments, the length of the notch may be about 1 mm, or 0.5 mm (or, in some embodiments, about 0.5 mm or less) to 2 mm (or, in some embodiments, about 2 mm or more than 2 mm), or 0.75 mm (or, in some embodiments, about 0.75 mm) to 1 mm (or, in some embodiments, about 1 mm), or any value within these ranges, or from any value to any value.

[0097] 19A and 19C are perspective and top views of the end of another embodiment of a cannula 412 that can be used with any embodiment of the device disclosed herein. FIG. 19B is a cross-sectional view taken through line 19B-19B of FIG. 19A of the embodiment of the cannula 412 shown in FIG. 19A. As shown, the cannula 412 can have a notch or cutout 414 formed at the end of the cannula 412, which allows any embodiment of the applicator portion disclosed herein to be easily deployed and / or retracted or folded. With reference to FIG. 18C, in some embodiments, the cutout 414 can have an asymmetric shape around a plane that extends through the axial centerline C of the cannula 412, for example, but not limited to, through the axial centerline C and through a plane perpendicular to the plane of the figure (e.g., perpendicular to the plane of the paper).

[0098] Further, in any embodiment, the notch 414 may be a double notch having a first portion 414a and a second portion 414b that is narrower than the first portion 414a. For example, and without limitation, the first portion 414a may have a width W1 that may be approximately twice the width W2 of the second portion 414b, or may be 50% greater (or approximately 50% greater) to 100% greater (or approximately 100% greater) than the width W2 of the second portion 414b. In any embodiment, the first portion 414a of the notch 414 can have a length L1 that is 50% (or about 50%) of the total length L of the notch 414, or a length L1 that is 30% (or about 30% or less than 30%) to 80% (or about 80% or less than 80%) of the total length L of the notch 414, or a length L1 that is 40% (or about 40%) to 60% (or about 60% or less than 60%) of the total length L of the notch 414. In some embodiments, the notch 414 can terminate in a curved end 416.

[0099] 21 is a top view of another embodiment of device 450 having an applicator 456 that can be used with any of the device embodiments disclosed herein. Device 450 and / or applicator 456 can include any of the components, features, materials, and / or other details of any of the other embodiments of the device or applicator disclosed herein, such as, but not limited to, device 100 and / or applicator 106 described above, in combination with or in place of any of the features described below to form new embodiments. With reference to FIG. 21, applicator 456 can have an applicator portion 460 coupled to a core member or elongated body 454 that extends through at least a portion (or all) of device 450.

[0100] 25, which is a cross-sectional view taken through line 25-25 in FIG. 21 of an embodiment of an applicator portion 460 that can be used in any embodiment of the device disclosed herein, such that the cross-section is perpendicular to the axial centerline of the applicator 456. As shown, some embodiments of the applicator portion 460 can have a symmetrical shape about a central plane C and can have a substantially uniform thickness across the entire width of the applicator portion 460.

[0101] 26 is a cross-sectional view of another embodiment of an applicator portion 470 that can be used in any embodiment of the device disclosed herein, the cross-section being perpendicular to the axial centerline of the applicator. As shown, some embodiments of the applicator portion 470 can have a symmetric shape about a central plane C, and the applicator portion 470 can have a tapered thickness that tapers from a first thickness T1 at the center of the applicator portion 470 to a second, smaller thickness T2 at one or both of the sides of the applicator portion 470. In some embodiments, as shown in FIG. 26, the bottom surface 472 and / or the top surface 474 of the applicator portion 470 can be angled from the center of the applicator portion 470 toward the side edges of the applicator portion 470. In other embodiments, as shown in FIGS. 27 and 28, the bottom surface 472 and / or the top surface 474 of the applicator portion 470 may be generally flat from the center of the applicator portion 470 toward the side edges of the applicator portion 470.

[0102] In any embodiment disclosed herein, the bottom and / or top surface of the applicator portion may be concave or curved from the center of the applicator portion 470 toward the side edges of the applicator portion 470. For example, without limitation, the top surface 484 of the applicator portion 480 may be curved from the center of the applicator portion 470 toward the side edges of the applicator portion, as shown in FIG. 27. In any embodiment disclosed herein, the central portion having a greater thickness (such as thickness T1) may be narrow, such as the central portion 486 of the embodiment of the applicator portion 480 shown in FIG. 27, or may be wider, such as the central portion 496 of the embodiment of the applicator portion 490 shown in FIG. 28 or the central portion 664 of the embodiment of the applicator portion 650 shown in FIG. 24. For example, and without limitation, the central portion can have a width of 30% (or about 30%) of the overall width of the applicator portion, or from 10% (or about 10% or less than 10%) to 60% (or about 60% or more than 60%), or from 20% (or about 20%) to 40% (or about 40%) of the overall width of the applicator portion.

[0103] In some embodiments, the first thickness T1 may be 0.2 mm (or about 0.2 mm), or 0.1 mm (or about 0.1 mm or less) to about 1 mm (or about 1 mm or more), or 0.15 mm (or about 0.15 mm) to about 0.5 mm (or about 0.5 mm), or any value or any value to any value within these ranges. In any embodiment, the second thickness T2 may be 0.1 mm (or about 0.1 mm), or 0.05 mm (or about 0.05 mm or less) to about 0.5 mm (or about 0.5 mm or more), or 0.075 mm (or about 0.075 mm) to about 0.25 mm (or about 0.25 mm), or any value or any value to any value within these ranges.

[0104] In some embodiments, the first thickness T1 can be 50% (or about 50%), or 10% (or about 10% or less than 10%) to about 80% (or about 80% or more than 80%), or 20% (or about 20%) to about 60% (or about 60%), or 30% (or about 30%) to about 40% (or about 40%), or any value within these ranges or from any value to any value.

[0105] Further, in any embodiment disclosed herein, the applicator portion 470 can have an asymmetric cross-section such that a first side of the applicator portion 470 has a different shape and / or thickness compared to a shape and / or thickness of a second side of the applicator portion 470, where the first and second side portions can be defined as being divided by a centerline axis C. For example, as shown in FIG. 29, which is a cross-sectional view of another embodiment of an applicator portion 500 that can be used in any embodiment of the device disclosed herein, a first shape and thickness profile of the first side portion 502 can be different from a second shape and thickness profile of the second side portion 504 of the applicator portion 500. The thickness T1 at the center can be greater than the thickness T2 at the side edge or side of the first side portion 502, and the thickness T3 at the side edge or side of the second side portion 504 can be greater than the thickness T2 at the side edge or side of the first side portion 502. Further, in any embodiment disclosed herein, the shape of the bottom surface 506 may be different from the shape of the top surface 508, the shape of the bottom surface 506 at the first side portion 502 may be the same as or different from the shape of the bottom surface 506 at the second side portion 504, and / or the shape of the top surface 508 at the first side portion 502 may be the same as or different from the shape of the top surface 508 at the second side portion 504.

[0106] 22 is a top view of another embodiment of a device 550 having an applicator 552 that can be used with any of the device embodiments disclosed herein. The device 550 and / or applicator 556 can include any of the components, features, materials, and / or other details of any of the other embodiments of the device or applicator disclosed herein, including but not limited to the devices 100, 450 and / or applicators 106, 456 described above, in combination with or in place of any of the features described below to form new embodiments. With reference to FIG. 22, the applicator 552 can have an applicator portion 560 coupled to a core member or elongated body 554 that extends through at least a portion (or all) of the device 550. With reference to FIG. 22, the applicator portion 560 can have a first tapered transition portion 562 and a second tapered transition portion 564. The first and second tapered transition sections can aid in folding, bending, rolling, coiling, or otherwise contracting the applicator portion as it is retracted into the cannula. In some embodiments, the first and second tapered transition sections 562, 564 can be symmetrical about the centerline C of the applicator portion 460. In other embodiments, the applicator portion can have tapered transition sections on both sides of the applicator portion, but these tapered transition sections can be of different sizes and / or shapes, such as the first and second tapered transition sections 656, 658 of the embodiment of the applicator portion 650 shown in FIG. 24. For example, but not limited to, the first tapered transition section can be longer than the second tapered transition section. In other embodiments, the applicator portion can have only one tapered transition section, such as the applicator portion 610 of the embodiment of the device 600 shown in FIG. 23.

[0107] 24, in any embodiment, an applicator portion (such as applicator portion 650) can be configured such that a length L1 of a first sidewall portion (e.g., sidewall portion 652, also referred to herein as a first side portion) can be less than the overall length L of the applicator portion due to the presence of a first tapered transition portion (such as first tapered transition portion 656). For example, the length L1 of the first sidewall portion can be about 40% of the overall length L of the applicator portion, or 30% or from about 30% to about 50% of the overall length of the applicator portion.

[0108] Additionally, the length L2 of the second sidewall (e.g., sidewall portion 654, also referred to herein as the second side portion) may be less than the length L1 of the first sidewall. This may be due to a difference in length, angle, and / or other shape of the second tapered sidewall portion (e.g., second tapered sidewall portion 658) and / or a larger radius at the intersection of the second wall portion with the second tapered sidewall portion. The radius at the intersection of the second wall portion with the second tapered sidewall portion (e.g., radius R2 in FIG. 24) may be significantly greater (e.g., 2-20 times greater or more, or 5-10 times greater or more, or any value or range of values ​​within the aforementioned ranges) than the radius at the intersection of the first wall portion with the first tapered sidewall portion (e.g., radius R1 in FIG. 24). In any embodiment, the second side transition portion 658 may be less steep than the first side transition portion 656 to allow the applicator portion to be easily folded or contracted.

[0109] In some embodiments, the first side portion 652 can have a first transition portion having a first axial length and the second side portion 654 can have a second transition portion having a second axial length, the second length being greater than the first length of the first transition portion. In some embodiments, the short length of the first transition portion can allow the first side portion 652 of the applicator tip 650 to collapse before the second side portion 654 of the applicator portion 650 collapses when the applicator portion 650 is retracted into the outer sleeve of the device. This can allow the applicator portion 650 to collapse to a more compact size in some embodiments as compared to a symmetrical applicator portion.

[0110] FIG. 30 is an end perspective view of another embodiment of a delivery device 700, showing an applicator 702 coupled to an inner cannula 704 and retracted or folded inside an outer cannula body or sleeve 706, and a substance delivery cannula 710 retracted inside the outer cannula body 706. FIG. 31 is an end perspective view of the embodiment of the delivery device 700 shown in FIG. 30, showing the applicator 702 in a partially advanced position and in an unfolded state. Additionally, FIG. 31 illustrates that in some embodiments, the delivery cannula 710 can be axially extended to extend to a distal end portion of the applicator portion 702, and can be retracted while the substance is oozing from the substance delivery cannula 710. The device 700 can be configured to limit the extent of extension of the substance delivery cannula 710 such that the substance delivery cannula does not extend beyond the distal end of the applicator portion 702. Additionally, device 700 may be configured such that substance delivery cannula 710 is in a fixed position at or near the end of sleeve 706 to allow delivery of substance onto a surface of applicator 702 as applicator 702 advances past the end of outer cannula or sleeve 706. In some embodiments, the only movable or extendable component of the device or distal end portion of the device may be the applicator and applicator portion, which may be integrally connected.

[0111] Although specific embodiments of the present invention have been described, these embodiments are presented by way of example only and are not intended to limit the scope of the present disclosure. Indeed, the novel methods and systems described herein may be embodied in a variety of other forms. Furthermore, various omissions, substitutions, and modifications may be made in the systems and methods described herein without departing from the spirit of the present disclosure. The appended claims and their equivalents are intended to cover any form or modification believed to be within the scope and spirit of the present disclosure. Thus, the scope of the present invention is defined solely by reference to the appended claims.

[0112] Features, materials, properties, or groups described in connection with a particular aspect, embodiment, or example should be understood to be applicable to any other aspect, embodiment, or example described here or elsewhere in this specification, except to the extent not inconsistent therewith. All features disclosed herein (including the accompanying claims, abstract, and drawings) and / or all steps of any method or process so disclosed may be combined in any combination, except combinations in which at least some of such features and / or steps are mutually exclusive. Protection is not limited to the details of any of the embodiments described above. Protection extends to any novel feature or any novel combination of features disclosed herein (including the accompanying claims, abstract, and drawings) or any novel step or any novel combination of steps of any method or process so disclosed.

[0113] In addition, certain features described in the present disclosure in the context of separate embodiments can also be implemented in a single embodiment in combination. Conversely, various features described in the context of a single embodiment can also be implemented in multiple embodiments separately or in any suitable subcombination. Furthermore, although some features may be described above as acting in a particular combination, one or more features from the claimed combination can be deleted from the combination in some cases, and the combination can be claimed as a subcombination or a variation of the subcombination.

[0114] Furthermore, although some operations may be illustrated in the figures or described herein in a particular order, such operations need not necessarily be performed in the particular order or sequential order shown, or all operations need not be performed, to achieve the desired results. Other operations not illustrated or described may be incorporated into the exemplary methods and processes. For example, one or more additional operations may be performed before, after, simultaneously, or between any of the described operations. Furthermore, operations may be rearranged or reordered in other embodiments. Those skilled in the art will appreciate that in some embodiments, the actual steps performed in the illustrated and / or disclosed processes may differ from those shown in the figures. Depending on the embodiment, certain of the steps described above may be omitted, or other steps may be added. Furthermore, the features and attributes of certain embodiments disclosed above may be combined in various ways to form further embodiments, all of which are within the scope of the present disclosure. Also, the separation of various system components in the above embodiments should not be understood as requiring such separation in all embodiments, and it should be understood that the components and systems described may generally be integrated into a single product or packaged into multiple products.

[0115] For purposes of the present disclosure, certain aspects, advantages, and novel features have been described herein. Not necessarily all such advantages are achieved in accordance with any particular embodiment. Thus, for example, one skilled in the art will appreciate that the present disclosure may be embodied or carried out in a manner that achieves one advantage or advantages taught herein without necessarily achieving other advantages that may be taught or suggested herein.

[0116] Conditional language, such as "can," "could," "might," or "may," is intended to convey that a particular embodiment includes certain features, elements, and / or steps, but another embodiment does not include them, unless otherwise specified or understood in the context in which it is used. Thus, such conditional language does not generally imply that features, elements, and / or steps are in any way required with respect to one or more embodiments, or that one or more embodiments necessarily include logic for determining whether those features, elements, and / or steps should be included in or performed in any particular embodiment, with or without user input or prompting.

[0117] Conjunctions such as the phrase "at least one of X, Y, and Z," unless otherwise noted, are understood in the context in which they are generally used to convey that an item, term, etc. may be either X, Y, or Z. Thus, such conjunctives are generally not intended to imply that a particular embodiment requires the presence of at least one X, at least one Y, and at least one Z.

[0118] As used herein, language of degree, such as terms such as "approximately," "about," "generally," and "substantially," refers to a value, amount, or characteristic that is close to a stated value, amount, or characteristic and still performs a desired function or achieves a desired result. For example, the terms "approximately," "about," "generally," and "substantially" can refer to an amount within a range of less than 10%, less than 5%, less than 1%, less than 0.1%, and less than 0.01% of a stated amount. As another example, in certain embodiments, the terms "approximately parallel" and "substantially parallel" refer to a value, amount, or characteristic that deviates from exact parallelism by no more than 15 degrees, 10 degrees, 5 degrees, 3 degrees, 1 degree, or 0.1 degrees.

[0119] The scope of the present disclosure is not intended to be limited by the specific disclosure of preferred embodiments here or elsewhere herein, but may be defined by the claims as they are presented here or elsewhere herein, or as they may be presented in the future. The language of the claims should be interpreted broadly based on the language used in the claims, and not limited to the examples described herein or during prosecution of the application, which examples should be interpreted as non-exclusive.

Claims

1. A device (100) for applying a bioadhesive material (101) to the retina, comprising: an outer sleeve (102, 202, 302, 402, 412, 422, 452) having a proximal end, a distal end (102a), a passageway (103) extending along the length of said outer sleeve, and an opening at said distal end of said outer sleeve; an elongate body (104, 208, 454, 554, 704) having a proximal end and a distal end; an applicator portion (310, 460, 560, 610, 650, 702) coupled to the distal end of the elongate body; an applicator tip (106, 156, 206, 306) comprising: a substance delivery lumen (105, 203, 340, 710) extending along a length of the device and through which a bioadhesive substance can be passed so that the bioadhesive substance can be applied to at least the applicator portion of the applicator tip; the applicator tip is configured to move between a first position in which the applicator portion is contained within the outer sleeve and a second position in which the applicator tip is positioned past the opening in the distal end of the outer sleeve; the applicator portion has a first width when the applicator portion is in the first position and a second width when the applicator portion is in the second position, the second width being substantially greater than the first width; the applicator portion is transformable between a first shape receivable within the passage of the outer sleeve and a second shape larger than the passage of the outer sleeve; A device wherein in the second configuration, the surface of the applicator portion is generally broad and flat, having a width and length greater than a thickness of the applicator portion.

2. The device described in claim 1, wherein at least the substance supply lumen is provided with a fluid-connected source of the bioadhesive substance.

3. An apparatus as described in claim 1 or 2, wherein the substance supply lumen is a separate lumen from the outer sleeve.

4. The device of any one of claims 1 to 3, wherein the substance delivery lumen is a passageway extending through at least the elongate body of the applicator tip.

5. 2. Apparatus according to any one of the preceding claims, wherein the substance supply lumen comprises a separate cannula disposed inside the outer sleeve and which is extendable and retractable relative to the outer sleeve.

6. 10. The device of claim 1, wherein the substance supply lumen is axially fixed relative to the outer sleeve and has an opening adjacent an end of the outer sleeve such that the bioadhesive substance can seep onto the applicator portion along at least a portion of the length of the applicator portion when the applicator portion is advanced distally.

7. 2. The device of any one of the preceding claims, further comprising a handle coupled to a proximal end of the outer sleeve.

8. 10. The device of any one of the preceding claims, wherein the applicator portion is biased such that a first side portion of the applicator portion curls toward a second side portion when the applicator tip is pulled back proximally into the outer sleeve.

9. 2. A device according to any one of the preceding claims, wherein the elongate body of the applicator tip extends through the outer sleeve to a proximal end of the device.

10. 10. A device according to any one of the preceding claims, wherein the elongate body of the applicator tip is integrally formed with or non-removably connected to the applicator portion.

11. 4. The device of any one of the preceding claims, wherein the applicator portion is biased to collapse within the passageway of the outer sleeve when the applicator portion is pulled proximally back into the outer sleeve.

12. 10. The device of any one of the preceding claims, wherein the applicator portion is biased such that a first side portion of the applicator portion folds or folds toward a second side portion when the applicator tip is pulled back proximally into the outer sleeve.

13. The passageway through at least the elongate body of the applicator tip comprises: i. an opening at the proximal end of the applicator portion; or ii. a plurality of openings through a first surface of the applicator portion; or iii. A device according to any one of the preceding claims, in communication with the opening at the proximal end of the applicator portion and the plurality of openings passing through the first surface of the applicator portion.

14. 10. The device of claim 1, wherein the applicator portion has an asymmetric shape such that a first side portion located on one side of an axial centerline of the applicator portion has a different shape than a second side portion located on the other side of the applicator portion, the first and second sides being separated by the axial centerline of the applicator portion.

15. the applicator portion has an asymmetric shape with a first length of a first side portion located on one side of an axial centerline of the applicator portion being longer than a second length of a second side portion located on a second side of the axial centerline of the applicator portion.

10. The apparatus of any one of the preceding claims, optionally wherein the first side portion has a first transition portion having a first axial length and the second side portion has a second transition portion having a second axial length, the first length of the first transition portion being less than the second length of the second transition portion.

16. 10. A device according to any one of the preceding claims, wherein the applicator portion has an asymmetric width; optionally, the applicator portion also has an asymmetric thickness.

17. the applicator portion has an asymmetric thickness in a width direction such that a thickness profile of the applicator portion at a first side of the applicator portion is different from a thickness profile of the applicator portion at a second side of the applicator portion.

10. A device according to any one of the preceding claims, optionally wherein the first side portion of the applicator portion is softer than the second side portion.

18. 10. The device of any one of the preceding claims, wherein the applicator portion is configured such that a first side portion contracts before a second side portion contracts when the applicator portion is pulled back into the outer sleeve.

19. the outer sleeve having a notch at the distal end of the outer sleeve; 5. The device of any one of the preceding claims, optionally wherein a notch is configured to facilitate contraction or reduction in size of the applicator portion as the applicator portion is retracted into the distal end of the outer sleeve.

20. the notch is generally "v" shaped or has a proximally narrowing tapered shape; or 20. The device of claim 19, wherein the notch is generally "u" shaped or has a uniform width and a rounded end at a proximal end of the notch.

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