Devices and methods for targeted delivery of substances

Abstract

To provide a device, a system, and a method for applying (coating) a substance such as a biological adhesive to a surface of an object.SOLUTION: A device for applying a bubble of a substance to a tissue surface 153 includes: a cannula; a distal tip 130 located at a distal end portion of the cannula and having a bubble support surface and an exit port extending through the bubble support surface; an expansion fluid passage extending through the cannula to the exit port; a supply source of an expansion fluid 105; and an actuator therefor. In some arrangements, the distal tip can be configured to support a layer of the substance 150 thereon over the distal port and the device can be configured such that the advancement of the expansion fluid from the fluid source through the exit port causes at least one bubble 146 of the substance to form on the distal tip, wherein the at least a portion of the bubble can be transferred to the tissue surface to treat a defect 151 on the tissue surface.SELECTED DRAWING: Figure 4C

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority under U.S.C. § 119(e) to U.S. Provisional Patent Application No. 62 / 700,768, filed July 19, 2018, and U.S. Provisional Patent Application No. 62 / 796,338, filed January 24, 2019. The entirety of both provisional applications is expressly incorporated herein by reference as if fully set forth herein.

[0002] Technical Field The systems, devices, kits and methods provided herein relate to the production of thin membranes for targeted delivery of therapeutic substances, which may be formed as bubbles. [Background technology]

[0003] Existing methods for fixing macular holes and retinal detachments associated with retinal discontinuities such as tears and holes include the use of perfluorocarbons, lasers, cryotherapy, gas bubble injection, and silicone oil. The use of perfluorocarbons to displace fluid from the subretinal space can result in inadvertent migration of perfluorocarbon liquid into the subretinal space, which, if located in the central macula, can lead to vision loss. Incomplete removal of perfluorocarbon liquid from the vitreous cavity can result in associated visual phenomena that patients may find uncomfortable. The use of lasers and cryotherapy can result in permanent retinal scar tissue formation and contribute to the formation of epiretinal membranes and epiretinal scar tissue. The use of gas bubble injection can limit patient activity and lead to complications such as elevated intraocular pressure and cataracts. Similarly, silicone oil can be problematic because it sometimes causes complications such as elevated intraocular pressure, requires a second surgery for removal, and often leaves behind residual oil bubbles after attempted removal, which can be visually distracting to patients.

[0004] Existing methods for securing leaking eyewall discontinuities, such as incisions, sclerotomy, and lacerations, include sutures and commercially available bioadhesives. Sutured discontinuities can sometimes continue to leak. Sutures can cause ocular irritation, pain, and tearing, and sometimes cause local tissue reactions, including episcleral and conjunctival edema and inflammation.

[0005] One drawback of some bioadhesives is that they may induce toxicity. Another drawback is that applying bioadhesives to the affected ocular surface, both inside and outside the eye, can be difficult due to the effects of gravity on the bioadhesive as it leaves the tip of the bioadhesive delivery device and other factors. For example, in eyes with retinal breaks located on the lateral or superior surface of the eye, gravity can make applying bioadhesives to retinal breaks difficult because gravity can cause the bioadhesive to drip or sag as soon as it is released from the applicator device, preventing accurate application of the adhesive onto the retinal discontinuity. The same problem arises when attempting to apply liquid or highly viscous materials to the lateral and inferior-lateral ocular surfaces. Another problem with bioadhesives is that they can be difficult to apply to large discontinuities in the retina and other ocular surfaces, as well as tissue discontinuities with irregularly shaped margins or margins at different heights. The challenges of applying bioadhesives to retinal discontinuities can be even more difficult when attempting to do so using a transscleral, subretinal approach. Summary of the Invention [Means for solving the problem]

[0006] The configurations disclosed herein optionally include devices, systems, and methods for applying (applying) a substance, such as a bioadhesive, to the surface of an object. The tissue may be biological or non-biological (e.g., non-living) tissue and may include medical scaffolds, patches, covers, implants, or other objects used in medical and non-medical applications. The object can be tissue, and thus the devices and methods disclosed herein apply a substance to the tissue surface. The tissue may be damaged tissue of any type or application disclosed herein, including, but not limited to, retinal tissue or other ocular tissue. As used herein, any feature, component, or other detail described in connection with a component, device, system, method, or any configuration thereof, is meant to apply to any other similar or suitable component, device, system, method, and arrangement disclosed herein.

[0007] As described, the devices, systems, and methods disclosed herein are configured to apply a substance (which may optionally be a bioadhesive) to a target tissue as a bubble, thin film, or other similar shape or configuration. Some non-limiting examples of applications of any of the devices and methods disclosed herein include applying a biomaterial, such as a bioadhesive, to ocular tissue, such as retinal breaks, holes, or detached retina; applying a bioadhesive to the sclera, conjunctiva, and cornea; applying a biomaterial, such as a bioadhesive, to gastrointestinal tissue, colonic tissue, etc., to seal perforations or breaks therein, air-filled ocular cavities or spaces, or other methods. However, the configurations of the devices and methods disclosed herein are not limited to the delivery of therapeutic substances or to medical or biological applications related to the eye. Any of the devices and methods disclosed herein may be used for the delivery of any desired or suitable substance or material in any desired application—biological, non-biological, mechanical, or other.

[0008] Any configuration of a device for applying a substance to tissue can optionally include a handle portion, an elongate body including a proximal end, a distal end, and an intermediate region extending therebetween, an outlet port at the distal end, and at least one fluid passageway (also referred to herein as a first passageway) in fluid communication with the outlet port. The fluid passageway can extend from the handle toward the intermediate region or beyond the distal end. The elongate body can also include a tubular member or cannula, which can have a proximal portion, a distal tip, and a body portion extending therebetween.

[0009] In any configuration, the system can include, consist of, or consist of a unitary device in which all of the system's components are connected (e.g., fluidly coupled) to one another. Additionally, in any configuration, the system can include, consist of, or consist of a non-unitary device in which one or more components of the system can be detached, removable, or provided entirely separate from other components of the system. Some configurations of the device may be modular, replaceable components.

[0010] A variety of materials can be used to construct the system and / or device. The handpiece or cannula, or components thereof, can include plastic, metal, polyvinyl chloride, glass, acrylic, carbon fiber, and / or wood.

[0011] The distal tip and / or end face of the distal tip in any of the configurations disclosed herein can have a retention ridge, lip, or rim with a flat surface configured to hold and retain the foam material. The end face of any of the devices disclosed herein can face circumferentially inward toward the center of the distal tip or have an inward-facing member extending circumferentially into the cannula exit port. This inward-facing member can be configured to hold the bioadhesive material and aid in the formation of a bioadhesive bubble or spherical film of bioadhesive material. The distal tip can have multiple end faces. In some configurations, the distal tip can have only one (or less) end face. The distal tip can be blunt or rounded, or have a blunt or rounded end.

[0012] The distal tip of any configuration can optionally have a periphery and four or more, two to eight, or four to six flaps extending inward across the cannula exit port. One or more of the flaps can have a beveled edge. A variety of materials can be used to manufacture the flaps, including, but not limited to, rubber, silicone, plastic, or elastomeric materials.

[0013] Some configurations of the system further include a substance supply channel within the device, or the substance supply channel can be advanced into the device to assist in the generation of gas bubbles in the bioadhesive. The substance supply channel can be internal or external to the inflation fluid passage of the device (sometimes referred to herein as a handpiece) and / or the fluid passage of the cannula. The substance supply channel can have an elongate body with a proximal end and a distal end with a substance supply tip and / or an exit port. The substance supply channel can be internal to or surrounded by at least a portion of the inflation fluid passage of the cannula body and / or the fluid passage at the base or tip of the cannula. One or more cannulas can have an outer wall, an inner wall, and a space between the inner and outer walls, which can optionally provide a boundary to the substance supply channel, and the space between the inner and outer walls includes the inflation fluid passage of the device, the fluid passage of the cannula body, or the fluid passage at the base or tip of the cannula. The material delivery tip can have an inclined surface relative to the longitudinal axis of the material delivery channel body and the material delivery outlet port. The end face of the material delivery tip can have an angle relative to the longitudinal axis of the material delivery channel body of 1 to 15°, 15 to 30°, 30 to 45°, 45 to 60°, 60 to 75°, 75 to 89°, 91 to 105°, 105 to 120°, 120 to 135°, 135 to 150°, 150 to 165°, or 165 to 179°, or a range including one or more of the foregoing angle ranges. The material delivery channel can have a material delivery tip that can have one, one to ten or more, or four to eight, or any number therebetween, or more material delivery tip outlet ports. The substance delivery channel may have a proximal end that extends into the fluid passage of the cannula, the gas flowing around the substance delivery channel when the gas is insufflated through the fluid passage of the cannula.

[0014] Some configurations of the system further include circumferential or non-circumferential intermittent support structures connecting the outer and inner walls, such as 2 or more, 4-8, or 6-10 or more, or any number in between, or more circumferential and / or non-circumferential intermittent support structures, which can be used to provide connections between inner and outer tubes, chambers, or walls of the system.

[0015] The substance delivery channel can surround at least a portion of the inflation fluid passage of the device, the fluid passage of the cannula body, or the fluid passage of the cannula base or tip. The cannula can have outer and inner walls and a space between the inner and outer walls, the space between the inner and outer walls can comprise the substance delivery channel, and the inner wall includes the inflation fluid passage of the handpiece, the fluid passage of the cannula body, or the fluid passage of the cannula base or tip.

[0016] The substance delivery channel can be a tube within the inflation fluid passage of the device, the fluid passage of the cannula body, and / or the fluid passage of the cannula base or tip. The substance delivery channel tube can extend within the cannula and can be advanceable to the distal tip of the device. The substance delivery channel tube can have a distal end that reaches near the cannula exit port.

[0017] The material delivery channel, the elongate body of the material delivery channel, the material delivery tip, and / or the material delivery outlet port can have any suitable size. The material delivery channel, the elongate body of the material delivery channel, the material delivery tip, and / or the material delivery outlet port can have any suitable length.

[0018] Some configurations of the system further include a second substance supply channel. For example, multiple internal supply chambers can be separated by support structures connecting the outer and inner walls. The substance supply channel and the second substance supply channel can each be configured to provide a separate substance, such as a polyethylene glycol solution and a trilysine amine solution. The substance supply channel and the second substance supply channel can each have a separate substance. For example, one chamber can contain a bioadhesive substance, and the other chamber can contain an activating substance. Other substances can also be provided in one or more chambers. For example, in one configuration, the first chamber contains a bioadhesive, the second chamber contains a sclerosing agent, and the third chamber contains a drug (e.g., an anti-inflammatory, antibiotic, etc.). It is contemplated that struts or support structures can separate two or more chambers. For example, a series of discontinuous struts can provide support by connecting the outer wall to the inner wall, or by connecting the outer wall of the distal tip to the outer wall of a fluid passage or substance supply channel within the distal tip.

[0019] Any configuration of the system can include a substance dispenser. The substance dispenser can have a base with a well or a series of wells. The base can be made of plastic, metal, or glass. Each well or series of wells can hold a substance, such as a bioadhesive substance.

[0020] Any suitable material can be used. The bioadhesive material can include ReSure sealant, polyethylene glycol hydrogel, polymer gel, bilayer hydrogel, cyanoacrylate-based material, fibrin glue, polyethylene glycol solution, or trilysine amine solution, as appropriate. The bioadhesive material can include a resin. In any configuration, the bubbles of material or the approximately spherical film of material encapsulating the inflation fluid can have any suitable diameter or size. The diameter can vary, expand, and / or decrease within, between, or within any of the aforementioned ranges.

[0021] Some configurations relate to a handheld device for applying a bioadhesive bubble to a retina, the handheld device comprising: an elongate body including a first end and a second end, the first end including a handle and the second end including a cannula including an exit port; at least one inflation fluid passage extending from the first end toward the second end; and a distal tip of the second end configured to generate a bioadhesive bubble from the bioadhesive when gas or liquid flows through the inflation fluid passage, to maintain the bubble on the distal tip when gas stops flowing through the inflation fluid passage, and to release the bubble when it rubs against the retina or when gas flows again through the inflation fluid passage, or the bubble can be released by heating or cooling the tip of the cannula or using a second instrument to detach the bubble from the distal tip.

[0022] Some configurations relate to a handheld device for applying a bioadhesive bubble to the retina, configured to generate the bioadhesive bubble from the bioadhesive as gas or liquid flows through the internal fluid passage, maintain the bubble on the distal tip when the gas stops flowing through the internal fluid passage, and release the bubble as it rubs against the retina or when the gas resumes flowing through the internal fluid passage, or when heating or cooling the tip of the cannula or using a second instrument to detach the bubble from the distal tip.

[0023] Some configurations relate to kits that include the systems or devices described herein. Some configurations of the kits further include a second system or device, each of which is disposable after a single or limited number of uses. Some configurations of the kits further include an adhesive biomaterial, a substance dispenser, and / or a tip plug or protective cover.

[0024] Some configurations relate to the use of a system, device, or kit for applying a bioadhesive bubble to an eye or retina, such as for eye or retinal repair. Some configurations relate to a method of repairing a retinal break, comprising using a system, device, or kit to generate a bioadhesive bubble comprising a substantially spherical film of bioadhesive material that encapsulates an inflation fluid, and applying the bioadhesive bubble from the system, device, or kit to the eye or retina.

[0025] Some configurations relate to a system for applying a bioadhesive foam to a retina or other biological tissue. The system can include a handpiece and / or a cannula. The handpiece can have an elongate body with a proximal end, a distal end, and an intermediate region extending therebetween, at least a proximal portion of the intermediate region can have a handle, and the distal end can include an outlet port and / or at least one inflation fluid passage in fluid communication with the outlet port and extending proximally toward the intermediate region. The cannula can include a cannula base, a distal tip, and / or a cannula body extending therebetween. The cannula body can include an inflation fluid passage in fluid communication with the exit port and a fluid passage configured to receive inflation fluid passed through the exit port, and the distal tip can have a flat, unbeveled surface with the cannula exit port at a distal end of the distal tip that is configured to support bioadhesive bubbles that are generated as inflation fluid flows through the inflation fluid passage to the cannula exit port at the distal end of the distal tip and through a bioadhesive substance contained within the handpiece or cannula, thereby creating a substantially spherical film of bioadhesive substance that encapsulates the inflation fluid. There can be no beveled surface at the distal tip or in the cannula exit port.

[0026] In a first aspect, a device for applying a bubble of a substance to a tissue surface includes a cannula having a proximal end, a distal end, and an intermediate portion extending therebetween; a distal tip at the distal end of the cannula, the distal tip having a bubble support surface and an exit port extending through the bubble support surface; an inflation fluid passage extending through at least the intermediate and distal portions of the cannula, the inflation fluid passage being in fluid communication with the exit port; a source of inflation fluid; and an actuator coupled to the source of inflation fluid, the actuator configured to selectively advance inflation fluid through the inflation fluid passage and the exit port upon actuation of the actuator. In an operable state, the distal tip can be configured to support a layer of substance on the bubble support surface such that the layer of substance completely covers the distal port. Additionally, when the device is in an operable state, the device can be configured such that advancement of inflation fluid from the fluid source through the exit port causes at least one bubble of the substance to form from the layer of substance on the bubble support surface of the distal tip. Additionally, the device can be configured to transfer at least a portion of the gas bubbles from the distal tip to the tissue surface to treat a defect on the tissue surface. This can be accomplished in any of the configurations disclosed herein by moving the cannula, distal tip, applicator portion, loop, or device or component over the tissue surface and / or defect in the tissue surface, thereby spreading the substance around the tissue surface and / or defect to a desired amount, which can be done in multiple steps.

[0027] The device for applying a bubble of a substance to a tissue surface can optionally include one or more of the following features in any combination: (a) the substance can be a bioadhesive; (b) the bubble surface includes a retention ridge, lip, and / or rim configured to support the bubble; (c) the bubble support surface includes a concave, curved depression; (d) the device can be configured to support a plurality of bubbles on the bubble support surface; (e) the device has a handle portion at a proximal end configured to support at least an actuator and a source of inflation fluid; (f) the device can be configured to form a bubble comprising a spherical film of substance that at least partially encapsulates inflation fluid advanced through an exit port; (g) the device can be configured to form a bubble comprising a spherical film of substance that only partially encapsulates inflation fluid advanced through an exit port; (h) the actuator includes a compressible bladder configured to expel inflation fluid from a source of inflation fluid within the bladder through an inflation fluid passageway and an exit port; (i) the above. The inflation fluid actuator includes a roller wheel movable along a compressible bladder configured to expel inflation fluid from a source of inflation fluid within the bladder through an inflation fluid passage and an outlet port; (j) the inflation fluid actuator includes a syringe; (k) further includes a substance delivery channel configured to deliver a substance to the distal tip of the device; (l) the substance delivery channel can be in fluid communication with a substance delivery source; (m) the substance delivery channel can be integrated within a cannula; (n) the substance delivery channel can be , an elongate body having a proximal end and a distal end, the distal end having a distal tip with at least one opening, the elongate body advanceable through the inflation fluid passage to the distal tip of the distal end of the cannula; (o) the substance delivery channel may be within or surrounded by at least a portion of the inflation fluid passage of the cannula; (p) the cannula includes an outer wall, an inner wall, and a space between the inner and outer walls, the inner wall having a substance delivery channel and the space having an inflation fluid passage of the device; (q) further having a second substance delivery channel;(r) the substance delivery channel and the second substance delivery channel each contain a distinct bioadhesive substance and / or an activator; (s) the bubble support surface may be sloped; (t) further comprising a substance dispenser; and (u) further comprising an ablation component configured to increase the temperature of at least the distal tip of the device;

[0028] In another aspect, a system for treating defects on a tissue surface includes a first device for generating bubbles of a substance for treating defects on a tissue surface, the first device including a first sleeve having a proximal end, a distal end, and an intermediate portion extending therebetween, a distal tip at the distal end of the first sleeve having an exit port extending therethrough, a fluid passage extending through at least the intermediate and distal portions of the first sleeve, the fluid passage being in fluid communication with the exit port, and a source of the substance.

[0029] The system for treating defects on a tissue surface may optionally include one or more of the following features in any combination: (a) the device is configured to support a layer of substance on an outlet port at a distal tip when the first device is in an operable state; (b) the first device may be configured such that, when the first device is in an operable state, passing a fluid through the outlet port causes at least one bubble of the substance to be formed from the layer of substance on the bubble-supporting surface at the distal tip, the bubble having a spherical film surface; (c) further comprising a second device for applying the bioadhesive substance to the retina, the second device having a second sleeve and an applicator, the second sleeve having a proximal end, a distal end, and a passageway extending along the length of the sleeve from the proximal end to the distal end of the sleeve, the applicator having an elongate body and an upper surface movable within the second sleeve. (d) the system may be configured so that at least one gas bubble can be transferred from the first device to the applicator tip of the second device and from the applicator tip of the second device to a tissue surface having a defect; and (e) the system may further include a patch removably supported on the surface of the applicator tip, the patch being supported so that at least one gas bubble can be transferred from the first device to the patch supported by the applicator tip of the second device and so that the patch can be transferred from the applicator tip of the second device to a tissue surface having a defect.

[0030] In another aspect, a method of repairing a defect in retinal tissue includes advancing a substance delivery device having a cannula and a distal tip toward the defect; providing a layer of bioadhesive substance over an exit port at the distal tip of the device such that the layer of bioadhesive substance completely covers the exit port; advancing an inflation fluid through the exit port and through the layer of bioadhesive substance to form a bubble of bioadhesive substance on a support surface of the distal tip, the bubble having a generally spherical film that can at least partially adhere to the support surface of the distal tip and that extends away from the support surface of the distal tip; and moving the bubble into the retinal tissue so as to at least partially cover the defect in the retinal tissue.

[0031] The method for repairing a defect in retinal tissue may optionally include one or more of the following features in any combination: (a) transferring a plurality of gas bubbles of a bioadhesive material to the defect and / or retinal tissue adjacent to the defect; and (b) transferring the gas bubbles to the retinal tissue so as to at least partially cover the defect in the retinal tissue includes transferring at least one gas bubble of the bioadhesive material to a first surface of a patch and positioning the patch over the defect such that the first surface of the patch having the bioadhesive material thereon can contact at least the retinal tissue adjacent to the defect.

[0032] In another aspect, a handheld device for applying a bioadhesive gas bubble to a retina has a proximal end with a handle, a distal end with a distal tip, and an internal air-fluid passageway from the proximal end to the distal end. The handheld device for applying a bioadhesive gas bubble to a retina can optionally include one or more of the following features in any combination: (a) the device can be configured to generate a bioadhesive gas bubble from the bioadhesive when gas flows through the internal air-fluid passageway; (b) the device can be configured to maintain an air bubble on the distal tip when gas stops flowing through the internal air-fluid passageway; and (c) the device can be configured to release the air bubble into retinal tissue when the device can be advanced to contact at least the retinal tissue.

[0033] In another aspect, a handheld device for applying a bioadhesive substance to a retina includes: a tubular body having a first end and a second end, an exit port at the second end, and a first passageway extending from the first end to the exit port; an elongate body having a loop at a distal end, the elongate body being advanceable and retractable within the first passageway such that the loop can extend from the exit port and contact a tissue surface of the retina; and a source of bioadhesive substance configured to be applied to the loop, the device being configured to apply the bioadhesive substance to the loop and transfer the bioadhesive substance from the loop to the tissue surface of the retina by contacting the tissue surface of the retina with the bioadhesive substance on the loop.

[0034] In another aspect, the use of the system, device, or method of any of the above aspects. [Brief explanation of the drawings]

[0035] [Figure 1] FIG. 1 is a side view of a non-limiting example of an apparatus for providing a substance. [Figure 2] FIG. 2 is a side view of the distal portion of the device shown in FIG. [Figure 3]FIG. 3 is a top view of the distal portion of the device shown in FIG. [Figure 4A] FIG. 4A is a side view of an example of a distal tip and a bubble formed from a substance. [Figure 4B] FIG. 4B shows the distal tip and bubble advancing toward the desired treatment location. [Figure 4C] FIG. 4C shows the distal tip and bubble being pressed into contact with the target tissue or surface defect at the desired treatment location. [Figure 4D] FIG. 4D shows the distal tip being withdrawn after the bubbles have burst or dissipated, depositing material onto the defect at the desired treatment location. [Figure 5] FIG. 5 is a cross-sectional view of a distal portion of a non-limiting example of a substance delivery channel. [Figure 6] FIG. 6 is a top view of the distal portion of the material delivery channel shown in FIG. [Figure 7] FIG. 7 is a top view of another non-limiting example of a distal portion of a substance delivery channel. [Figure 8] FIG. 8 is a cross-sectional view of another non-limiting example of an apparatus for providing a substance. [Figure 9] FIG. 9 is a cross-sectional view of another non-limiting example of a distal portion of a device for providing a substance. [Figure 10] FIG. 10 is a cross-sectional view of another non-limiting example of a distal portion of a device for providing a substance, showing bubbles formed from the substance. [Figure 11] FIG. 11 is a side view of a non-limiting example of a cannula. [Figure 12] FIG. 12 is a cross-sectional view of a non-limiting example of a distal tip. [Figure 13] FIG. 13 is a cross-sectional view of a non-limiting example of the interior of a distal tip having grooves. [Figure 14] FIG. 14 is a side view of a non-limiting example of the exterior of a distal tip having grooves. [Figure 15] FIG. 15 is a cross-sectional view of another non-limiting example of a distal tip. [Figure 16A]FIG. 16A is a cross-sectional view of a non-limiting example of an apparatus for providing inflation fluid, the apparatus including a roller wheel and a compressible bladder. [Figure 16B] FIG. 16B is a top view of the apparatus for providing inflation fluid shown in FIG. 16A. [Figure 17] FIG. 17 is a cross-sectional view of a non-limiting example of an apparatus for providing inflation fluid that includes a compressible bladder. [Figure 18] FIG. 18 is a top view of another non-limiting example of an apparatus for providing inflation fluid that includes a compressible bladder. [Figure 19] FIG. 19 is a top view of a non-limiting example of an apparatus for providing inflation fluid that includes a movable slider. [Figure 20] FIG. 20 is a side view of an apparatus for providing inflation fluid including a movable slider. [Figure 21] FIG. 21 is a side view of a non-limiting example of a distal tip including a flap. [Figure 22] FIG. 22 is a top view of the distal tip shown in FIG. [Figure 23] FIG. 23 is a cross-sectional view of a non-limiting example of an apparatus for providing a substance. [Figure 24] FIG. 24 is a cross-sectional view of another non-limiting example of an apparatus for providing a substance. [Figure 25A] FIG. 25A is a cross-sectional view of another non-limiting example of a device for providing a substance, showing the loop in an extended position. [Figure 25B] FIG. 25B is a cross-sectional view of the device shown in FIG. 25A showing the loop in a retracted position within the cannula. [Figure 26] FIG. 26 is a top view of a non-limiting example of a system or device having a transscleral tip. [Figure 27] FIG. 27 is a cross-sectional view of a distal portion of a non-limiting example of an apparatus for providing a substance. [Figure 28] FIG. 28 is a cross-sectional view of a distal portion of another non-limiting example of an apparatus for providing a substance. [Figure 29]FIG. 29 is a side view of a distal portion of another non-limiting example of a tip cover. [Figure 30] FIG. 30 is a side view of a non-limiting example of a cannula with one or more fibers or wires for light or cauterization. [Figure 31] FIG. 31 is a first side view of a distal portion of a non-limiting example of a cannula. [Figure 32] FIG. 32 is a second side view of the cannula shown in FIG. [Figure 33] FIG. 33 is a top view of a non-limiting example of a material dispenser configuration. [Figure 34] FIG. 34 is a front view of the material dispenser configuration shown in FIG. [Figure 35] FIG. 35 is a cross-sectional view of a distal portion of another non-limiting example of a cannula. [Figure 36] FIG. 36 is a cross-sectional view of another non-limiting example of a cannula. [Figure 37] FIG. 37 is a cross-sectional view of another non-limiting example of a cannula. [Figure 38] FIG. 38 is a side view of a non-limiting example of a distal tip. [Figure 39] FIG. 39 is a side view of a non-limiting example of a distal tip with an air bubble. [Figure 40] FIG. 40 is a side view of a non-limiting example of a distal tip. [Figure 41] FIG. 41 is a side view of a non-limiting example of a distal tip with material within the distal tip. [Figure 42] FIG. 42 is an end view of a non-limiting example of a system or device described herein. [Figure 43] FIG. 43 shows a non-limiting example of a system having an applicator device and a substance delivery device. [Figure 44] FIG. 44 is a top view of a non-limiting example of an applicator device showing the applicator tip of the device in an open position. [Figure 45] FIG. 45 is an end view of the applicator device shown in FIG. 44, showing the applicator tip of the device in a closed position. [Figure 46] FIG. 46 is a side view of a non-limiting example of an applicator device and a substance delivery device, showing the substance delivery device depositing a bubble of substance against the surface of a patch supported by the applicator tip of the applicator device. [Figure 47] FIG. 47 is another illustration of a system having an applicator device and a substance delivery device. DETAILED DESCRIPTION OF THE INVENTION

[0036] In the following detailed description, reference may be made to the accompanying drawings, which form a part thereof. In the drawings, like numerals typically identify like components unless otherwise contradictory in context. The exemplary configurations described in the detailed description, drawings, and claims are not meant to be limiting. Other configurations 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 and illustrated in the figures herein, can be arranged, substituted, combined, separated, and designed in a wide variety of different configurations, all of which are expressly contemplated herein.

[0037] The compositions disclosed herein include devices, systems, and methods for applying a substance to a surface, including a tissue surface. In any of the compositions disclosed herein, the substance can be a therapeutic substance that can be applied to tissue. The tissue in any of the compositions can be ocular tissue. 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 treatment substances, bilayer hydrogels, non-solids, etc. As used herein, any use of the term substance is intended to include any of the types and examples of substances disclosed elsewhere in this disclosure.

[0038] Any of the configurations of the systems, devices, and methods disclosed herein can be configured to generate thin films of a substance for delivery to biological tissue, including, but not limited to, ocular tissue such as a retinal tear or detachment, or intraocular, intraperitoneal, intracranial, or epidermal bioadhesive delivery. However, the configurations of the devices, systems, and methods disclosed herein are not limited to delivery of substances to ophthalmic, medical, or biological applications. The devices, systems, and methods disclosed herein can be used for any desired or suitable delivery, in any desired or suitable biological, non-biological, mechanical, or other application.

[0039] Some configurations include creating a gas bubble from the adhesive, e.g., spraying the gas bubble. The gas bubble can include a thin film that can be applied to a surface, such as the retina, which can be attached to or detached from the back of the eye. In any configuration, the gas bubble can be applied to the surface of the retina in an air-filled eye or in a fluid-filled eye. Advantages of applying the bioadhesive in this manner include an improved ability of the adhesive to conform and adhere to the eye and retina, and reduced or improved drying, curing, or activation times for the adhesive.

[0040] The configurations of the devices and methods disclosed herein are configured to allow for the generation of a gas bubble(s) in a controlled manner, such that the release of the gas bubble(s) from the delivery device can be controlled so that they are not released until a desired time. Additionally, the devices and methods disclosed herein are optionally configured to allow for the reformation of gas bubbles or the new formation of gas bubbles after the formation of one or more gas bubbles during a previous operation of the device has removed and dissipated the film, preparing for the next operation. The devices disclosed herein may optionally be configured to be used in any orientation, including, but not limited to, horizontal, vertical, inverted (inverted), etc., to allow for use with any desired tissue, including ocular tissue, the oral wall or palate, the nose, vagina, or other tissue.

[0041] As used herein, the term "bubble" can mean a perfectly spherical membrane or body of material, a spherical or curved shape or film of a surface, including, but not limited to, a hemisphere of material, a single bubble, or multiple bubbles that are either separate or connected together such as as a foam. All uses of the term "bubble" herein are meant to include any one or all of these examples of bubbles described in this paragraph or elsewhere herein.

[0042] For example, but not by way of limitation, any of the devices disclosed herein can be configured to form bubbles, meaning that the device can be configured to form a spherical membrane or body of material, a spherical or curved shape or film of a surface, examples of bubbles including, but not limited to, a partial or hemispherical shape of material, a complete sphere of material, a single bubble, or multiple bubbles that are either separate or connected together such as a foam.

[0043] In any of the configurations disclosed herein, the bubbles or roughly spherical films of bioadhesive material may have diameters ranging from about 0.1 mm to about 15 mm or more (up to at least 100 mm), or from about 0.5 mm to about 5 mm, or from about 1 mm to about 3 mm, or any value within these ranges.

[0044] Some configurations relate to systems and / or devices for generating a bioadhesive bubble and / or applying the bioadhesive bubble to a surface. The surface can be a biological surface such as the retina. The system or device can optionally include an elongate body having a handle portion and a distal port. The elongate body can have a proximal end, a distal end, and an intermediate region extending therebetween. At least the proximal portion of the elongate body can include the handle portion. The distal end of the elongate body can have an exit port. In any configuration, the elongate body, which can be a cannula as described in more detail below, can include at least one inflation fluid passageway, or optionally multiple (e.g., two, three, or more) inflation fluid passageways extending partially or completely through the elongate body. The inflation fluid passageway(s) can be in fluid communication with the exit port and extend proximally toward the intermediate region of the elongate body.

[0045] In any configuration, the fluid passage can be configured to allow a fluid, which can be a gas or other inflation medium, to be supplied through the body of the device toward an outlet port. The fluid passage can be in fluid communication with the outlet port. In any configuration, the fluid, such as a gas or other inflation medium, can be advanced through the fluid passage to exert a positive pressure on the material, causing it to expand or form a curved or spherical film or one or more gas bubbles from the material.

[0046] The inflation medium can, for example, inflate or otherwise expand a film or membrane of material (optionally, a bioadhesive material) prior to applying the bioadhesive to the targeted tissue or tissue region. In some configurations, the surgeon can activate a source of inflation medium (which can be a gas) and supply inflation fluid through the inflation passage. The inflation fluid can pass through the device and exit through the material through an opening at the distal end of the device to create a gas bubble and / or spread a film of material over the desired surface.

[0047] 1 shows a non-limiting example of an applicator device 100 that can be used to provide a substance (e.g., including, but not limited to, a bioadhesive) to a target tissue. Device 100 can include a handle 102 that includes an inflation fluid source 104, which can optionally include a bladder, which can be coupled to a body member 106 having a fluid passageway 107 extending therethrough. It should be understood that other inflation fluid sources can be used, such as air / gas supply lines other than bladders, or other types of inflation fluid sources disclosed herein or used in the industry or now or later developed.

[0048] Inflation fluid source 104 can be filled with inflation fluid 105 that can be used to generate bubbles. Inflation fluid source 104 can be in fluid communication with fluid passageway 107 such that the inflation fluid can be selectively released or communicated from inflation fluid source 104 through fluid passageway 107. Body member 106 can optionally be formed from flexible, rigid, semi-rigid, or other suitable materials or components.

[0049] In any of the configurations disclosed herein, the inflation fluid can include a gas such as air, sulfur hexafluoride (SF), perfluoropropane (CF), and / or nitrogen or other inert gas, or any combination thereof. The inflation fluid can include a liquid such as water, a heavy liquid such as perfluoro-n-octane, a buffer, a solvent, and / or an oil such as silicone oil. The inflation fluid enters and / or fills the cells of the bioadhesive material and / or expands the cells as the inflation fluid enters and / or fills them. The inflation fluid can include 5-50%, 10-15%, 10-20%, 10-30%, 5-25%, 5-15%, 15-25%, 15-20%, 20-25%, 20%, about 20%, 12%, about 12%, 14%, about 14%, 12-14%, or 11-15% SF. The inflation fluid can include 5-50%, 10-15%, 10-20%, 10-30%, 5-25%, 5-15%, 15-25%, 15-20%, 20-25%, 20%, about 20%, 12%, about 12%, 14%, about 14%, 12-14%, or 11-15% C3F8. For example, the inflation fluid can include 20% SF6, 12% C3F8, and 68% air, or the inflation fluid can include 20% SF6, 14% C3F8, and 66% air. The inflation fluid can also include liquids such as water, heavy solvents or liquids such as perfluoro-n-octane, oil, or oil-water mixtures.

[0050] A connector 110 may be coupled to the end of body member 106 to allow for selective connection and disconnection of an end piece 114, which may be or may include a cannula. Connector 110 may include a connector portion 116, which may be optionally threaded, configured to reversibly couple with a proximal end 118 of cannula 114. In any configuration, connector portion 116 may have an opening 120 or passage therethrough, which may be threaded and configured for threaded engagement with the proximal portion 118 of cannula 114. In some configurations, opening 120 may have female threads arranged to engage with male threads on the proximal portion 118 of cannula 114. Optionally, connector 110 may have male threads thereon configured to engage with female threads inside the proximal portion 118 of cannula 114.

[0051] Connector 110 may optionally include a luer lock connector configured to reversibly connect with cannula 114. Cannula 114 may have a generally uniform or consistent cross-sectional size along its length. In some configurations, as shown, a proximal portion of cannula 114 may have an increased cross-sectional size or diameter compared to intermediate and distal portions of cannula 114. Cannula 114 may have a passageway 122 therethrough that may be in fluid communication with openings or passageways 120 in connector 110 and passageway 107 through body member 106. Cannula 114 may have an end 130 (also referred to herein as a distal tip) having an opening 132 therethrough that is in fluid communication with passageway 122 extending through cannula 114.

[0052] Additionally, device 100 may optionally include one or more valves 140, such as one-way valves or other flow restrictors, located anywhere along the length of passageway 107. Valves 140 may prevent leakage or inadvertent discharge of inflation fluid 105 within passageway 107 or inflation fluid source 104 and / or may be configured to prevent backflow into source 104. One or more such valves may also be located in cannula 114.

[0053] It should be noted that the components shown in Figure 1 and some other figures are not drawn to scale. For example, in other configurations, cannula 114 may be longer or shorter than that shown in Figure 1, or may have a larger or smaller cross-sectional size compared to the example shown in Figure 1.

[0054] In any configuration, connector 110 can be configured to engage with any of a variety of different cannulas 114. The various different cannulas 114 can have a variety of different cross-sectional sizes and / or shapes, a variety of different lengths, and a variety of other different features and characteristics. With reference to device 100 shown in FIG. 1, distal tip 130 of cannula 114 can be smaller or larger than shown in FIG. 1 relative to one or more of the other components, including connector 110 and body member 106.

[0055] Cannula 114 can include a proximal portion or base 118, a distal tip 130, and a body 119 extending therebetween. As described, cannula 114 can have an inflation fluid passage 122 extending through the cannula body. Fluid passage 122 can be configured to be in fluid communication with outlet port 130 and to conduct inflation fluid 105 via inflation fluid passage 122 and outlet port 132.

[0056] As inflation fluid flows through a material located in or on the distal tip 130 of the cannula 114, it can create a bubble or curved film or membrane of material that partially or completely encases or encapsulates the inflation fluid. In some configurations, the curved film or membrane of material can completely encase the inflation fluid and can have a spherical shape. The surface(s) of the distal tip 130 of the cannula 114 (which can be, but need not be, angled or sloped) allow the material (which may be in the form of a bubble) to be removed from the cannula 114 and deposited on the target tissue (e.g., a retinal break) with high precision and reduced risk of further tissue trauma. Additionally, any of the devices disclosed herein, including device 100, can be configured to maintain a bubble on the distal tip when gas stops flowing through the inflation fluid passage and / or release the bubble when the bubble can brush against the retina or when gas resumes flowing through the inflation fluid passage.

[0057] The distal tip can have at least one surface (referred to herein as a support surface or end face) 131 configured to support a film of material, followed by bubbles of material. The end face (or faces, in some configurations, there can be multiple end faces) 131 can optionally be angled relative to the longitudinal axis of the cannula body and / or at least one cannula exit port. The at least one end face 131 can be configured to support a film of material (which can be a bioadhesive in any embodiment disclosed herein). The film of material can be manipulated by fluid advancing through the fluid passage 122 to change from a first shape or configuration to a second shape or configuration having a spherical or curved shape, or in the form of one or more bubbles of material. For example, in some configurations, the second state of the film can be formed when inflation fluid is selectively advanced through the fluid passage 122 to the at least one cannula exit port 132 and / or through material contained within the handpiece or cannula, thereby generating a substantially spherical or curved film of material. In configurations where the material is in the form of gas bubbles in the second state, the gas bubbles can completely surround the volume of inflation fluid.

[0058] The end surface 131 may be substantially planar, as shown in FIG. 2. For example, FIG. 2 shows a side view of a distal tip 130 with a flat, angled bubble port, and FIG. 3 shows a top view thereof. The illustrated distal tip may also have a substance-retaining rim 133. The exit port 132 may be coplanar with the end surface 131 or may be at an angle of about 30°, about 40°, or from about 30° or less to about 45° or more relative to the longitudinal axis extending through the cannula 114. As shown in FIGS. 2 and 3, the entire rim of the cannula exit port 132 may be substantially coplanar with the end surface 131. The substance-retaining rim 133 of the end surface 131 may be configured to support the bubble as it forms, expands, and seats on the substance-retaining rim 133. The substance-retaining rim 133 may be configured to prevent material from escaping from the distal tip 130 as the device is maneuvered toward a target tissue surface or eye.

[0059] FIG. 4A shows an example of the formation of a bubble 146 containing a substance 150 filled with inflation fluid 105 on the distal tip 130 of the device. The substance 150 is shown on the rim of the distal tip 130. The bubble was formed by passing inflation fluid 105 through the distal opening 132 of the device, which was covered by a film or layer of substance 150. As the inflation fluid 105 continues to advance through the distal opening 132, the film or layer can stretch and move into a spherical or bubble-like shape, either drawing more of the substance 150 used to form the bubble 146 into the bubble, as shown in FIG. 4A, or stretching existing material as the bubble expands. The bubble 146 is formed as the inflation fluid 105 advances through the passageway 122 of the cannula 114 and through the distal port 132. The inflation fluid 105 fills the interior space within the bubble 146.

[0060] Once the bubble 146 has been formed or expanded to a desired size or thickness, the surgeon or user can then advance the distal tip 130 of the device containing the bubble to the desired treatment location, as shown in Figure 4B. The distal tip 130 of the device can be used to advance the substance-containing bubble 146 in a controlled manner toward a defect 151 in tissue or an object surface 153, as shown in Figure 4B. The bubble 146 may then be pressed into further contact with the defect 151 (which may be a retinal defect) or surface 153 of the object by further advancing the distal tip 130 toward the defect, causing the bubble to elongate and spread the substance over the defect 151 and target surface 153.

[0061] The gas bubble 146, and therefore the substance 150, can then be released from the distal tip in a number of different ways. For example, the gas bubble can be caused to burst against the target tissue surface by continuing to advance the distal tip 130 toward or against the target tissue surface and / or defect, or by continuing to expand the gas bubble. The distal tip can be made of a hydrophobic or other material configured to repel the substance against the distal tip or reduce the surface tension of the substance so that at least a portion, or most, or substantially all, of the substance used to form the gas bubble can be deposited on the defect or against the target tissue surface. Additionally, as described below with reference to FIG. 43 , the applicator device 1002 can be used to remove the gas bubble from the distal tip and / or to apply or burst the gas bubble against the defect or target surface. Furthermore, in some configurations, movement of the distal tip relative to the target surface can exert a shear force on the gas bubble, which can cause the bubble to burst or dissipate and be deposited against the target surface. In some configurations, a needle or other piercing element (both of which can optionally have blunt or sharp ends) or other suitable piercing device can be advanced through or away from the distal tip toward the bubble to burst the bubble against the target tissue surface. Additionally, any of the other devices or components described herein configured to facilitate release of bubbles from the distal tip can be used to facilitate release of bubbles from the distal tip.

[0062] Optionally, the distal tip 130 of the device can be moved proximate to the defect or target location before the bubble has fully, partially, or substantially expanded, so that the bubble can expand only against the defect or target surface. The distal tip 130 can then be retracted or withdrawn from the target location, leaving the material 150 deposited against the target surface 153 to cover the defect 151, as shown in FIG. 4D .

[0063] Any configuration of the device or method disclosed herein can include a liquid reservoir or chamber along with means for applying liquid from the reservoir to a film retaining member (such as a ring or loop, such as a flexible loop) or the distal end of the cannula to form a film thereon, so that each time the device is actuated and / or the film is removed by touching the retina, additional liquid to provide a new film can be applied to the ring, thereby preparing the device for the next use by retracting the ring.

[0064] In any configuration, the substance can be provided from a reservoir, which can be in the form of a cartridge, absorbent material, or chamber, which can be removably attached to, integral with, or otherwise in the device, or can be advanced into an internal passageway of the device, such as an inflation fluid passageway. The device can optionally be configured so that when the cartridge or chamber becomes emptied, it may be easily replaced with a full cartridge, absorbent material, or chamber in a dual configuration.

[0065] Any of the configurations disclosed herein can have a substance supply lumen or chamber within the handle portion and / or cannula, or can be advanceably positioned within the handle and / or cannula (such as, but not limited to, cannula 114). The substance supply channel can be configured to advance a substance to the distal tip of a cannula, such as cannula 114. In some configurations, as shown in FIGS. 5 and 6 , the substance supply channel can have a separate elongated body portion that can be advanced distally through the inflation fluid passage of the cannula to the distal tip of the cannula, such that the substance can be discharged from the end of the substance supply channel and onto an opening in the distal tip of the cannula to provide and / or replenish the substance on the distal tip for formation of a bubble element. Optionally, the substance supply channel can be advanceable and retractable within the inflation fluid passage of the cannula as needed. In some configurations, as shown in FIG. 7, one or more substance delivery channels may be formed in the wall portion of the cannula so that a steady supply of substance can be provided to the distal tip without the need for a separate device for providing the steady supply of substance.

[0066] 5 and 6, in some configurations, the substance supply channel or tube 158 can have a separate elongate body 160 that can be advanceable within the inflation fluid passage of the cannula (not shown in FIG. 5). The elongate body 160 can have a passage 162 extending through its length that can be in fluid communication with a distal opening or port 163. The distal port 163 can extend through the distal end 164 of the supply channel 158. Thus, the body portion 160 can be sized and configured to be unrestrictedly advanceable through the inflation fluid passage of the cannula with which the supply channel 158 is configured to function. For example, the elongate body 160 of the supply channel 158 can be about 20% smaller than the inner diameter of the inflation fluid passage of the cannula, or about 2% to about 20% or more, or about 5% to about 10% smaller than the inner diameter of the inflation fluid passage of the cannula. The distal end 164 of the supply channel 158 may have a shape and angle that generally matches the shape and angle of the inner surface of the inflation fluid passage and the end portion of the inner surface of the interior of the cannula, and may be slightly smaller in size than the inflation fluid passage.

[0067] The supply channel 158 can advance distally within the inflation fluid passageway within the bubble generator cannula so that its distal end 164 is adjacent to or contacts the end of the internal passageway. The substance can then advance through one or more openings 163, creating a film across the distal port of the bubble generator. In this manner, the substance can be spread across the distal port. The supply channel 158 can be used in this manner to fill the tip of any cannula or device disclosed herein with the substance. The end face may have multiple substance delivery holes (as shown in FIG. 7) or a single hole 163 as shown in FIGS. 5 and 6. Each hole may be large enough to occupy more than 50% of the end face 163 of the substance supply channel tip, for example, and not by way of limitation, or small enough to occupy 5-25% or less than 50% of the end face 164 of the angled tip of the substance supply channel. Some configurations may have five or more holes, or from four to about ten or more holes, at the distal end of the delivery channel.

[0068] Some configurations of the system, device, cannula, or distal tip include a space below the substance-retaining rim 133 and the substance delivery channel 158. This space can be configured to allow the bioadhesive substance to coalesce from the substance delivery channel 158.

[0069] As discussed above and shown in FIG. 7 , any configuration of delivery channels disclosed herein can include a material delivery tip with any desired number of openings 163 at its distal end, including one opening, two openings, three openings, four openings, five openings, six openings, seven openings, or up to 20 openings or more, or between five and ten openings, or any number between any of the aforementioned values. As discussed above, the material delivery channel can include a proximal end that extends into the fluid passage of the cannula. The material delivery channel can be sized to allow inflation fluid to flow around the outer surface of the material delivery channel when inflation fluid is insufflated through the fluid passage of the cannula.

[0070] In some configurations, the cannula can optionally include an outer wall, an inner wall, and a space between the inner and outer walls, where the inner wall includes the substance delivery channel and the space includes an inflation fluid passageway of the handpiece, a fluid passageway of the cannula body, or a fluid passageway at the base or tip of the cannula. The substance can be advanced through the innermost lumen or inside the inner wall, as needed. The substance delivery tip can include a surface that can be angled relative to the longitudinal axis of the substance delivery channel body and the substance delivery outlet port, depending on any of the other angled tip details disclosed herein, or otherwise.

[0071] Another example of a cannula 170 having an internal material supply passage 172 is shown in Figure 8. The cannula 170 can optionally have multiple material supply passages 172 extending through the cannula 170, which can be integrally formed with the cannula and configured to allow passage or advancement of material from a proximally located material source or reservoir to an opening 176 in the distal tip 178. The arrows through the material supply passages 172 in Figure 8 indicate the direction of material flow through the material supply passages 172 as the surgeon or user advances material through the material supply passages 172. The material supply passages 172 can optionally communicate with a manifold 180 that surrounds the opening 176 in the distal tip 178. Manifold 180 can be sized and configured to create a film or membrane of material across opening 180 at distal tip 178 as the material advances through passageway 172, such that bubbles 186 can form from the film or membrane of material as inflation fluid advances through inflation fluid passageway 184 of cannula 170. Manifold 180 can have a series of radially inwardly projecting openings, annulus, openings, or jets that can be configured to facilitate the formation of a film of material. Cannula 170 can be formed as a single piece or from multiple pieces connected together. Openings 176 can be sized and configured to ensure consistent formation of bubbles as inflation fluid passes through the material and / or consistent formation of a film of material delivered through passageway 172.

[0072] As mentioned above, any configuration of the devices disclosed herein can be configured so that the material delivery channel surrounds at least a portion of the handpiece inflation fluid passage, the cannula body fluid passage, and / or the cannula base or tip fluid passage. As shown in FIG. 9 , for example, the device 200 can have an elongated body portion 202 having an inflation fluid passage 204 extending therethrough. The inflation fluid passage 204 can be partially or completely surrounded by a material delivery channel or lumen 206 that can be used to advance material to the distal tip 210 of the device 200. The lumen 206 can be a single annular lumen or can include one or more openings at the proximal and distal ends or portions of the lumen 206 that are all in communication. In some configurations, deflector(s) 212 can be positioned at the distal end of lumen 206 and can be configured to direct the flow of material radially inward toward openings 216 at the distal end of device 200. The deflectors can optionally have an annular shape. The deflectors can be angled inward at an angle less than about 90° or can have angled surfaces to provide a more efficient flow path of material toward openings 216.

[0073] The device 200 can optionally include a continuous (360°) circumferential deflector member 212 or multiple discrete deflector members. The deflector member can be configured to allow for longer retention of the air bubble on the tip of the cannula. This configuration allows the fluid to flow around the inflation fluid (which in any configuration disclosed herein may be air, sterile air, or another inert gas, or other fluids described herein) to form a film of material at the cannula exit port 216. After the film is formed, inflation fluid can be advanced against the film to form an air bubble. FIG. 10 shows that an air bubble is formed from a film of material advancing through the material delivery channel or lumen 206. The air bubble may be supported by a flared opening.

[0074] In other configurations, the substance delivery channel can include a tube or cannula that can be advanced within the handpiece inflation fluid passage 362, the cannula body fluid passage, or the cannula base or tip fluid passage. The substance delivery channel tube can be advanced toward the cannula exit port to contact the distal tip or within the distal tip. The substance delivery channel tube can have a distal end that reaches near the cannula exit port.

[0075] Any configuration of the systems and / or devices disclosed herein can further include a second substance delivery channel, which can each contain a separate bioadhesive substance, such as a polyethylene glycol solution and a trilysine amine solution, a hydrogel, a bilayer hydrogel, or a polymer hydrogel.

[0076] At least one end surface can be configured to support a bioadhesive bubble. The end surface, retention ridge, lip, or rim can include a flat surface configured to hold and / or maintain the bioadhesive bubble. The distal tip and / or an end surface of the distal tip can include a retention ridge, lip, or rim with a flat surface configured to hold and maintain the bioadhesive bubble.

[0077] The end face of the distal tip can have an angle relative to the perpendicular end (in either direction) of 1-15°, 15-30°, 30-45°, 45-60°, 60-75°, or a range including two or more of the foregoing angle ranges relative to the longitudinal axis of the cannula body and / or at least one cannula exit port. The angle of the end face can be configured to enhance retention of the bioadhesive bubble so that the bubble can be prevented from escaping.

[0078] The distal tip in some configurations can be configured without a bevel. For example, the distal tip may comprise a flat or perpendicular surface with the cannula exit port at 90° relative to the longitudinal axis of the cannula body, or the distal tip may be rounded and / or blunt without a flat surface.

[0079] Any configuration of the distal tip and / or end face of the distal tip can include a retention ridge, lip, or rim for retaining or supporting a bubble. Additionally, the size, angle, and / or shape of the distal tip (such as distal tip 130 or any other distal tip disclosed herein) and its retention ridge, lip, or rim can be based on the application and other factors related to the substance, including, but not limited to, the viscosity of the substance. For example, the substance retention rim 133 may be thinner (e.g., 1 mm) for a viscous substance than for a non-viscous substance (e.g., 2.5 mm). In other configurations, the substance retention rim 133 can be thicker when configured for a lower viscosity substance than when configured for a higher viscosity substance. The cross-sectional shape of the port 132 can optionally be circular, square, oval, rectangular, triangular, pentagonal, hexagonal, star-shaped, or other shape. The shape can be selected based on the viscosity of the bioadhesive substance and the size or other parameters of the desired bubble(s) or foam to be formed.

[0080] The end surface 131 may be flat, curved, or otherwise configured and may have a depression (recess) formed therein that slopes toward the opening 132. The depression may be inwardly curved, have a flat cross-sectional profile, or may be curved. Any of the configurations disclosed herein may have multiple openings 132 formed in the distal end to allow for the simultaneous formation of multiple bubbles of material or to form a foam-like structure of the material. Any of the configurations may have two or more openings, or from 2 to about 20 or more openings, or from 4 to 12 openings, or any value within these ranges.

[0081] 11 and 12 illustrate another configuration of a cannula 250. An end surface 252 of a distal tip 254 of the cannula 250 can optionally be circular, oval, non-circular, or other shape. For example, the distal tip 254 can optionally be circular, square, or rectangular in shape. Additionally, the distal tip 254 can have a non-flat end surface 252, as shown in FIGS. 11 and 12. The end surface 252 can be angled inward toward the center of the cannula 258. The end surface 252 can have a bevel (chamfer) or angle formed around an opening 256. The opening 256 can be in fluid communication with an inflation fluid passageway 258 through the cannula 250. End face 252 may be at an angle A (as shown in FIG. 12) that is about 45° relative to longitudinal axis C (as shown in FIG. 12), or may be in the range of about 30° or less to about 90° or more relative to longitudinal axis C, or about 40° to about 70°, or about 50° to about 60°, or any value within these ranges.

[0082] Additionally, cannula 250 can have a hub or hub portion 260 and connector threads 262 on its exterior (as shown) or interior surface. The cannula can optionally include a solid cannula wall, a substance delivery channel or core or cannula fluid passageway 258 through which inflation fluid can be advanced, an opening or cannula exit port 256 at the tip of the cannula, and a space 264 configured to maintain a film of a substance, such as a bioadhesive substance. As with any configuration disclosed herein, cannula 250 can be dipped into a substance dispenser, as described below, to add substance to the distal tip of the cannula, and the bioadhesive substance can be retained as a film within space 264 at the tip.

[0083] Thus, in any configuration, the end of the cannula (whether beveled, right-angled, or otherwise) can have a concave or inwardly curved depression formed in its end surface. Alternatively, in any configuration, the end of the cannula (whether beveled, right-angled, or otherwise) can have a convex or outwardly curved depression formed in its end surface. The end surface may be flared or flanged at the end and / or may include spaces to hold or provide a larger surface area for the bioadhesive material. An advantage of a flared or flanged surface is that it can hold the film of bioadhesive material from forming bubbles when gases such as air are blown into and / or against the film.

[0084] Some configurations of the distal tip can have multiple end faces. Some configurations of the distal tip can have only one (or less) end face, while in other configurations, multiple end faces are used. The distal tip can be blunt or rounded, or can include a blunt or rounded end.

[0085] The tip can include, for example, one or more grooves at the distal tip. An advantage of having grooves at the distal tip is that the one or more grooves can help retain the bioadhesive material and aid in bubble formation in the bioadhesive material. The distal tip can include 1 to 10 grooves, or 3 to 6 grooves (e.g., 5), or any number within or greater than these ranges. The distal tip can include an inner surface that includes grooves. For example, FIG. 13 shows a side view of another configuration of a cannula 300 having multiple grooves 302 formed on the inner surface of the distal tip 304. The distal tip 304 can optionally include an outer surface 306 that also or alternatively has one or more grooves 310, as shown in FIG. 14, which is a side view of a distal tip having multiple grooves 310 on the outer surface of the distal tip. Any configuration can have ridges, grooves, or other patterns of protrusions and / or depressions on the inner or outer surface of the tip of the cannula, optionally including the end face, to help retain material in and / or on the tip of the cannula. The ridges, grooves, or other patterns may be configured to retain or hold air bubbles in place.

[0086] In any configuration, the cannula, cannula base, cannula body, and / or distal tip can have a cross-sectional diameter ranging from about 0.1 mm to about 10 mm or more, or from about 1 mm to about 4 mm, or from about 1.5 mm to about 2 mm, or any value therein. In some configurations, the cannula, cannula base, cannula body, and / or distal tip can have a cross-sectional diameter that is 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. The cannula, cannula base, cannula body, distal tip and / or cannula exit port can have a length of about 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. The cannula, cannula base, distal tip, and / or cannula exit port can include an outer diameter, an inner diameter, and a width between the inner and outer diameters, each of which is 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. Any of the components or features disclosed herein can have any suitable or typical size, including, but not limited to, any size within any of the ranges described herein.

[0087] The retaining edge, ridge, or lip can be 0.1-0.5 mm, 0.5-1 mm, 1-2 mm, 2-3 mm, 3-4 mm, 4-5 mm, or 5-10 mm thick. The retaining edge, ridge, or lip can be 0.1-0.5 mm, 0.5-1 mm, 1-2 mm, 2-3 mm, 3-4 mm, 4-5 mm, or 5-10 mm long. Some configurations include a retaining edge, ridge, or lip that can be set back a short distance from the most distal tip of the cannula. The distal tip may or may not have a central air tube.

[0088] In any configuration, the opening may be at the very tip of the distal tip. Optionally, the opening may be on a side of the tip of the distal tip. The opening may be on a side of the distal tip but proximal to the tip of the distal tip.

[0089] Some configurations of the present systems and / or devices include circumferential or non-circumferential intermittent support structures. The intermittent support structures can connect the outer wall to the inner wall. Some configurations can include 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 4-10, or any number of circumferential and / or non-circumferential intermittent support structures. Some configurations can include circumferential or non-circumferential intermittent support structures connecting the outer wall and the inner wall, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or any number therebetween, or more. 15 shows an example of a distal tip 350 that includes intermittent attachments or support structures 352 between a central tube 354 and an outer tube 356. The support structures can be configured to allow fluid to pass around such structures.

[0090] The handpiece or cannula may include an outer wall, an inner wall, and a space between the inner and outer walls, such as space 358 in cannula 350. The space between the inner and outer walls may include a substance delivery channel. The inner wall may bound an inflation fluid passage 362 in the handpiece, a fluid passage 362 in the cannula body, or a fluid passage 362 in the cannula base or tip.

[0091] In any configuration, inflation fluid can be provided from a source separate from the device, or from a reservoir, cartridge, or absorbent material within or incorporated into the device. As described, any configuration can have a fluid passageway through which gas can be advanced from the source. The device can optionally have a connector at its proximal end, such as a port to which a tube or other conduit can be attached, to allow pressurization of the contents within the device (e.g., inflation fluid), with or without a plunger or moveable plug. Any configuration of handpiece or device disclosed herein can include an inflation fluid actuator. The inflation fluid actuator can be coupled to the proximal end of the device so as to be in fluid communication with the inflation fluid passageway. The inflation fluid actuator can be configured to be actuated or moved by a user. The moving component can be configured such that actuation of the moving component by a user causes flow or movement of inflation fluid through the inflation fluid passageway, for example, from the proximal end to an outlet port at the distal end. The handpiece can include an inflation fluid actuator connected to the inflation fluid passage at the proximal end and configured to be engaged by a user, which engagement can cause movement of inflation fluid through the inflation fluid passage from the proximal end to an outlet port at the distal end.

[0092] The inflation fluid actuator can optionally include a roller wheel or roller ball that can be advanced and retracted to advance or retract fluid through the inflation fluid passage. In this configuration, the roller wheel device can include a plurality of movable ribs or spokes coupled with a cylindrical outer surface configured to rotate about a central axis. In any embodiment disclosed herein, the roller wheel can be configured to expel inflation fluid from the bladder through the inflation fluid passage from the proximal end to an outlet port at the distal end when the roller wheel is rotated or moved along the length of the tube or chamber by, for example, a person's finger, a small motor, a coil spring, or other means.

[0093] A non-limiting example of an inflation fluid actuator 500 that can be used with any of the device configurations disclosed herein is shown in FIGS. 16A and 16B. The actuator 500 can have a roller wheel 502 configured to travel along the length of the inflation fluid conduit 504 and squeeze the inflation fluid conduit 504 to flatten and / or collapse (crush) the inflation fluid conduit 504 as the roller wheel 502 travels along the length of the inflation fluid conduit 504. As this occurs, the roller wheel 502 can force fluid within the passageway 506 distally toward the distal tip of the cannula, where the fluid can come into contact with a film of material, such as a bioadhesive, and generate an air bubble. The conduit 504 can be made from elastic tubing that collapses as the roller wheel 502 advances along the length of the conduit 504, or even from inelastic, single-use tubing. In any configuration, the roller wheel 502 can roll in both a distal and proximal direction, drawing air back into the passageway 506 when the roller wheel is moved proximally. The actuator 500 can also optionally include a second roller coupled to the first roller wheel and coupled to roll with the first roller to apply an opposing force to the tube squeezing the tube between the first and second rollers. Some configurations include a roller ball that can be movable 360 ​​degrees around a point or axis, forward and backward, or in any bounded or unbounded manner.

[0094] Some configurations include a fixed device where the bladder moves relative to a ball, sphere, stopper, plunger, or other stop device. For example, some such configurations include a port in the handle configured to receive an adhesive substance within the handle, where the adhesive-containing bladder can be configured to be moved from a distal to a proximal direction, and the ball creates a barrier to the contents of the bladder, thus causing the expulsion of the bioadhesive through the distal end of the device. Some configurations include a bioadhesive packet that may be loaded into the device.

[0095] As described, the handpiece can further include a source of inflation fluid connected at its proximal end to the inflation fluid passage, which can include an inflation fluid actuator. The inflation fluid actuator can be configured to be engaged directly or indirectly by a user, and such engagement can cause movement of inflation fluid through the inflation fluid passage from the proximal end to an outlet port at the distal end. In some configurations, the inflation fluid actuator can include a compressible bladder, a syringe, a collapsible vial, or other reservoir, such as an accordion-type collapsible reservoir, or other similar device arranged to expel inflation fluid from the bladder through the inflation fluid passage from the proximal end to the outlet port at the distal end of the device. In some configurations, the inflation fluid actuator can include a roller wheel movable forward and backward and configured to expel inflation fluid from the bladder through the inflation fluid passage from the proximal end to the outlet port at the distal end.

[0096] In yet additional configurations, the inflation fluid actuator can have a sliding piece, such as a plunger. In some configurations, the inflation fluid actuator can include a syringe filled with inflation fluid, such as air. Optionally, the inflation fluid actuator can include a compressed fluid or gas cartridge, such as a compressed air cartridge, that can be fluidly coupled to the inflation fluid passage. A trigger, valve (bulb), stopcock, or other device or component can be used to control the flow of air from the compressed air cartridge to the inflation fluid passage.

[0097] The inflation fluid actuator can optionally include a compressible bladder. The compressible bladder can be configured to expel inflation fluid from the bladder through an inflation fluid passageway from the proximal end to an outlet port at the distal end. The inflation fluid actuator can include a compressible bladder configured to expel inflation fluid from the bladder through an inflation fluid passageway from the proximal end to an outlet port at the distal end. The compressible bladder can have a diameter extending out from the center of the handle on one or more sides of the handle or another portion of the handle (e.g., the elongated body) that is 1 to 1.5 times, 1.5 to 2 times, 2 to 3 times, 3 to 4 times, or 4 to 5 times the diameter of the other portion of the handle (e.g., the elongated body). For example, the compressible bladder can extend 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 10 to 15, 15 to 20, or more degrees from the side of the handle or the elongated body of the handle. The compressible bladder can include any flexible material, such as rubber, plastic, flexible metal, or elastic material.

[0098] FIG. 17 shows a side view of an embodiment of an inflation fluid actuator 520 that can be used with any of the device configurations disclosed herein to provide inflation fluid to the distal end or tip of a cannula and, therefore, to a substance for forming a bubble. The fluid actuator 520 configuration shown in FIG. 17 can include a compressible bladder 522 having an interior air space 523 in fluid communication with an inflation fluid passage 524 of an inflation fluid channel 526. The bladder 522 can extend or protrude from one side of the handle, such as from the top of the handle, so that a user can apply a generally unidirectional force F to collapse the bladder 522 and advance inflation fluid through the inflation fluid passage 524. The actuator 520 can have a support or support surface for the compressible bladder at the bottom of the compressible bladder. The support for the compressible bladder can include the handle or an intermediate support structure of the device or system, depending on the configuration. The bladder can be compressible, for example, with a person's finger, to force air out of the bladder.

[0099] Some configurations can include an actuator mechanism with a compression device that includes a normally expanded, resilient air reservoir valve, thus forcing air distally through the air tube, toward the distal tip of the cannula, or through a bubble-forming ring at the end of the device. Some configurations can include a trigger mechanism that compresses the air reservoir valve from one side. Some configurations can include a trigger mechanism that compresses the air reservoir valve from two or more sides simultaneously. The valve can be made of a material that can be sufficiently resilient to return the trigger to its normal position, although if desired, a small coil spring can be coupled to the trigger to maintain it in its normal, unactuated position and return it to such position after each actuation.

[0100] The device may include a cannula and associated distal tip that is separate from the bubble-generating portion of the device and allows for air to be blown onto the retina to create a drying effect prior to application of the bubbles. In some configurations, the device may be configured to allow the device to blow air through the distal tip of the cannula without the presence of a substance so that the air is blown onto the target tissue.

[0101] FIG. 18 illustrates another configuration of an actuator 540 that can be used to advance inflation fluid toward the distal end of the cannula of any of the device configurations disclosed herein. In any configuration, the actuator 540 can have a bladder 542 having a volume of space 543 therein that is in fluid communication with a passageway 544 through an inflation fluid conduit or channel 546. The bladder 542 can be arranged with flexible ribs or struts, corrugations, or otherwise to improve the flexibility and collapsibility (crushability) of the bladder. The ribs can be configured to help the bladder 540 retain its shape and resilience and / or to bias the bladder back to its expanded shape. The ribs can be made of the same material as another portion of the compressible bladder, or the same material as the remainder of the compressible bladder, or can be made of a different flexible material.

[0102] In any configuration, actuator 540 can have one or more one-way valves in fluid communication with the bladder to allow air to refill the bladder when it is released and inflates back to its original expanded state and to prevent air from being sucked back into bladder 542 from the distal portion of conduit 546. Bladder 542 can be sized to have any desired volume of inflation fluid contained therein. Bladder 542 can be squeezed or otherwise compressed in any direction to expel inflation fluid toward the distal tip.

[0103] In some configurations, the bladder 542 may be spherical or approximately spherical and may extend radially in all directions away from the centerline of the conduit 546. In other configurations, the bladder 542 may have a hemispherical shape or any other desired shape.

[0104] Any configuration of the systems and / or devices disclosed herein can include a separate or electrically driven means for advancing inflation fluid through the inflation fluid passage of the handpiece or through the inflation fluid passage of the cannula. For example, the inflation fluid passage can include a proximal end connected to a tube, channel, or other passage configured to connect to and receive inflation fluid from an inflation fluid receptacle. The receptacle can include a valve. The valve can be configured to open by operation of a button on the handpiece of the system or device or by operation of a foot pedal. The valve can be configured to open by manual operation, such as through operation of a screw handle.

[0105] In any configuration, the inflation fluid actuator may include a slider. The slider or other inflation fluid actuator can be configured to move a plunger, such as a plunger, toward the distal end of the device. Movement of the plunger can force inflation fluid through an inflation fluid passage and / or outlet port of the handpiece and / or through a cannula inflation fluid passage and / or cannula outlet port of the cannula to generate bubbles.

[0106] 19 and 20 illustrate a non-limiting example of an inflation fluid actuator 560 comprising a sliding piece 562. The sliding piece 562 may include a movable portion or slider 562 that may be coupled to a sealed diaphragm, piston, plunger, or other similar component disposed within a chamber 570 of the actuator 560 and capable of moving with the movement of the slider 562, thereby varying the volume of space within the chamber 570. The chamber 570 may optionally have a generally cylindrical shape, at least in its middle portion. The slider 562 may be configured to move along a channel or groove 564 from a proximal end 566 a to a distal end 566 b of the device, thereby expelling air or inflation fluid through an inflation fluid passageway of the device or system. It should be understood that the slider 562 may be movable in both directions, thus allowing for control of the amount of inflation fluid expelled from the device.

[0107] In some configurations, moving slider 560 toward the proximal end of the device can be configured to draw air from the passageway to which chamber 570 is connected, to reduce the volume of air bubbles or otherwise draw fluid from the cannula's fluid passageway. However, in some configurations, one or more one-way flow valves can be placed in fluid communication with the chamber to prevent air from being drawn from the cannula as slider 560 moves toward the proximal end of the device. The chamber can be refillable using a sterile or filtered ambient or another fluid source, or from a separate source, when the slider moves proximally or from a separate source.

[0108] The device 560 can be handheld. The distal end 566b can be tapered. As the slider 560 is moved from the proximal end 566a toward the distal end 566b, the fluid in the chamber 570 can be forced through the device to apply pressure to a film of material, which can be a liquid, gel, or some other non-solid composition, that can hang across the opening in the distal end 566b. This can form a bubble of material from the hole in the tapered distal end 566b. The film of material can be formed across a ring that can be positioned inside the distal end of the device. In other configurations, fluid (e.g., gas) can be forced from the chamber 570 toward the distal tip of a cannula of any other configuration disclosed herein by moving the slider 562 toward the distal end 566b of the device.

[0109] Some configurations may optionally include a mechanism for locking the trigger mechanism once a bubble is generated, allowing operation of the device within the eye without having to maintain pressure on the trigger to avoid bubble deflation. Additionally, in some configurations, a diaphragm, plunger, or piston within chamber 570, or any other chamber, such as a cylindrical chamber formed as part of or attachable to the handle portion, can be moved by a rotating or twisting action, for example, by turning a dial or other threaded component, to move the diaphragm, plunger, or piston within the chamber, thereby forcing inflation fluid out of the chamber and into the cannula. Due to the threaded nature of the actuator, a device of this configuration can resist inadvertent movement due to backpressure caused by an air bubble and can provide greater resolution and control by the user regarding the amount of air evacuated from the chamber.

[0110] In some configurations, both the proximal end or the distal end can optionally include an opening that may generate a gas bubble. Optionally, either the proximal end or the distal end (but not both) can include an opening for generating a gas bubble. Both the proximal end and / or the distal end can include multiple openings that may generate multiple gas bubbles simultaneously.

[0111] Any of the device configurations disclosed herein can include a one-way flow valve that can be configured to allow fluid, such as inflation fluid or a substance, to flow distally and prevent backflow (i.e., proximal flow) of the fluid or substance when the pressure on the proximal side of the valve is greater than the pressure on the distal side of the valve.

[0112] Some configurations include a mechanism for locking the actuator mechanism once a bubble is generated, or for preventing any backflow of fluid towards the proximal end of the device once a bubble is generated, in which state the device can be steered and manipulated by the surgeon (e.g., optionally within the eye) without having to maintain pressure on the trigger to avoid deflation of the bubble.

[0113] The distal tip of any configuration disclosed herein can include one or more flaps adjacent to or covering the distal port of the device. For example, the distal tip can include four flaps, or two to eight or more flaps, or three to six flaps. The flaps can be connected to the periphery at or adjacent to the distal tip of the device and / or can extend across the cannula exit port.

[0114] 21 and 22 show another configuration of a device 590 having an opening 592 extending through a distal surface 593 of the distal end of the device, the opening 592 being in fluid communication with a passageway 594 extending through the device. One or more bendable, resilient flaps 596 (four are shown) selectively cover the opening 592. The flaps 596 can be made of silicone and can form a diaphragm over the opening. The flaps 596 can act or function as a valve. As shown in FIG. 22, the flaps 596 can include a slit 595, a rounded or beveled edge, and / or a hole. One or more of the flaps can optionally each include a beveled edge.

[0115] A silicone diaphragm having one or more slits and / or a central hole may be used with any of the various cannula or applicator tips described herein. The silicone diaphragm can function as a valve to retain a substance inside and / or to control bubble formation. Any slit or hole in the center of the silicone diaphragm may be of any shape. The flap may comprise rubber, silicone, plastic, or an elastic material.

[0116] Any handle configuration disclosed herein can have an interface portion. The interface portion can include a mating end. The mating end can be configured to reversibly or irreversibly couple with a proximal portion of any cannula or elongate body configuration disclosed herein. The proximal portion of the cannula can be configured to reversibly couple with the mating end of the elongate body or the interface portion of the handle. When the handle has an elongate body, the elongate body can include an interface portion, which includes a mating end configured to interact with the proximal portion of the cannula.

[0117] The handle, cannula, or any component thereof, or other components of the device, may be made from or can include plastic, metal, polyvinyl chloride, glass, acrylic, carbon fiber, and / or wood. The distal tip plug or protective tip cover can include plastic, metal, polyvinyl chloride, glass, acrylic, carbon fiber, and / or combinations thereof, or any other suitable material. The handpiece or cannula, or components thereof, can be minimally, moderately, or maximally thermally conductive.

[0118] The elongate body, cannula, exit port, and / or inflation fluid passage of the handpiece can have a cross-sectional diameter, size, or width of about 20 mm to about 50 mm, or about 25 mm to about 40 mm, or 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. The handpiece or handle can have a length ranging from about 4 cm to about 12 cm or more, or from about 6 cm to about 9 cm, or any value within these ranges. The cannula can have a length ranging from about 0.5 cm or less to about 10 cm or more, or from about 2.5 cm to about 5 cm.

[0119] Additionally, in any configuration, injection and / or aspiration of the bioadhesive substance and / or activating solution can be controlled manually or with a foot pedal. Thus, any configuration disclosed herein can include a foot pedal. The foot pedal can be configured to release air or inflation fluid through a tube or channel into the inflation fluid passageway so that the air or inflation fluid can flow toward and through the distal portion of the device to form a bubble at the distal tip of the device.

[0120] A liquid retaining member in the form of an annular wire ring can be used with any of the cannula configurations disclosed herein. This ring can optionally be secured to the tip of the distal end of the device by angled arms. The liquid retaining member (also referred to herein as a ring) need not be an annular ring and can take any desired shape. The liquid retaining member can be adapted to retain a bubble-forming liquid thereover. When liquid is applied to the ring, a film of the liquid can form over the ring and be held in such position until displaced from the ring by air or other pressure.

[0121] In some configurations, the angled arms can be made integral with the ring. The arms can extend along a portion of the length of the body of the device. The angled arms of the ring can be attached to the device using any suitable component or means. The ring has an attachment, which can be button-like or any other suitable shape, that can extend outside the central core of the device so that it can be easily manipulated with a finger(s). The attachment can be used to move the angled arms and attached ring distally and proximally.

[0122] Some configurations include a ring or rings that provide a means for holding a film of material across the space within the ring that can form a bubble(s) when a stream of air or gas is directed at the film of material to form bubbles. In some configurations, the ring may be stationary or may be immersed in a liquid to form a film across the ring. Some configurations include a stationary ring where a liquid may be actively distributed across the central opening of the ring. The ring may be a hollow reservoir capable of holding a fluid and having one or more openings inside the ring that allow fluid to be injected through the hollow ring and then exit the ring through openings inside the ring, creating a film of liquid across the ring opening and allowing bubbles to form as gas passes through the ring.

[0123] An air tube can be mounted axially within the device to direct air flow against the film, which can be held across the ring. The distance between the ring and the end of the air reduction tube controls the effect of the bubble(s) that form. The volume and velocity of the air passing through the tube (which can be controlled by the diameter of the tube's outlet end) can also affect the results. If the tube end is too close to the ring, the force of the air flow may only displace the liquid film without forming a bubble(s). This can cause the film to rupture. On the other hand, if the distance between the ring and the end of the tube is too large, the air flow will dissipate before reaching the film, and no bubbles will form. By optimizing the distance between the air tube and the ring, a bubble or series of bubbles may form upon depression (squeezing) of the valve (the size of the bubble can be controlled by the size of the retaining ring), or a single large bubble may form with each operation of the valve. Therefore, the desired effect can be achieved by adjusting the distance between the ring and the tube and by controlling the size of the tube's diameter.

[0124] Some configurations of the system and / or device can include a loop. The loop can be retractable, e.g., the loop extends from an end of the device, such as the distal end, and can be partially or completely retracted proximally within the distal tip of the device to change the size and / or shape of the loop. The loop can be retracted within the handle, cannula, or distal tip, depending on the configuration. The loop can include a wire. The loop or wire can include a metal, such as iron, steel or stainless steel, titanium, nitinol, platinum, or another material, such as plastic. The ring can be configured so that a substance fills the wire loop or forms a film on the wire loop. The adhesive can fill or form a film on the wire loop when the wire loop is retracted and / or expanded, depending on the configuration. The film can extend or evacuate from the distal tip into the loop.

[0125] The system or device can be configured so that the wire loop can be applied to a retinal break or tear after the bioadhesive material forms a film on the flexible loop. Some configurations include methods of applying a flexible loop having a film of bioadhesive material to a retinal break or tear. When the wire with the film is placed on a surface, such as a retina or retinal break, the device and material can be configured so that the film adheres to the surface (to a greater extent than the film adheres to the loop) and can be displaced from the loop.

[0126] The loop can be non-flexible and / or non-retractable. The wire or loop can have a thickness ranging from about 0.02 mm to about 1 mm, or from 0.01 to 0.02 mm, 0.02 to 0.05 mm, 0.05 to 0.1 mm, 0.1 to 0.5 mm, 0.5 to 1 mm, 1 to 2 mm, 2 to 3 mm, 3 to 4 mm, or 4 to 5 mm, or any combination of the above thicknesses. For example, the loop can optionally comprise a flexible suture material, such as polypropylene or collagen suture, and can have one of the diameters described above. Suitable sutures include, but are not limited to, sutures having a USP designation of 11-0, 10-0, 9-0, 8-0, 7-0, 6-0, 5-0, 4-0, 3-0, 2-0, 0, 1, 2, 3, or 4. The loop can have a diameter of 1-2 mm, 2-4 mm, 4-6 mm, 6-10 mm, 10-20 mm, or 20-30 mm, or a range including any combination of the above diameters.

[0127] 23 shows an example of a system and / or device that may have a plunger 602, a handle 604, a cavity 606 for holding a bioadhesive material, an elongated knob 608, a rod 612, a locking connector 616, and a flexible loop 620 configured to accommodate a film of bioadhesive material. The loop 620 shown in FIG. 23 may optionally be configured to extend further than shown.

[0128] When plunger 602 is advanced distally by a user (e.g., using pressure from the user's finger or air pressure supplied by an external device connected to the handle), it may be used to expel bioadhesive material through the hollow cannula and / or into flexible loop 620. For example, extension knob 608 may be used to extend the rod, and thus flexible loop 620, from a retracted position as seen in FIG. 23 to a more extended position, or even to a more retracted position. Knob 608 and rod 612 may be interlocking such that rotation of the knob in a first direction engages teeth on the knob with teeth on the rod, advancing the rod distally. Rotation of the knob in a second direction engages teeth on the knob with teeth on the rod, retracting the rod proximally. For example, knob 608 may take the form of a roller wheel with teeth on its surface, or a roller wheel with a smooth surface, which, when rolled, can cause movement of the rod either distally or proximally. The teeth may optionally be oriented parallel to the axis of rotation of the knob / roller wheel (not shown).

[0129] Alternatively, the knob and rod may be smooth but may be in contact such that rotation of the knob in a first direction causes the rod and loop to advance distally, and rotation of the knob in a second direction causes the rod to retract or retract proximally. Any of the loop configurations disclosed herein can be used to support a film of a substance (e.g., a bioadhesive) that can be applied to ocular tissue. This can be used with or without the introduction of an inflation fluid, and thus with or without using the loop to form one or more bubbles. The loop can be placed in contact with or moved relative to a target tissue, for example, to deposit a substance carried by the loop on the target tissue.

[0130] Additionally, in any configuration, the loop can be temperature controlled (i.e., cooled or heated) to change the adhesive or cohesive properties of the film adhesion of the material to the loop, allowing for detachment from the film and / or allowing for stronger adhesion to the film. For example, but not by way of limitation, the wire can be heated or cooled to any desired temperature using a heating or cooling element in communication with the loop to facilitate release of the material from the loop.

[0131] In some configurations, a gas bubble can be formed from the material held by the loop. Additionally, in such configurations, release of the gas bubble can be achieved by tightening or closing the loop (by retracting the loop, advancing a clasp, cinch, or other fastening device to tighten the loop, or by other methods), narrowing the loop and drawing the gas bubble away, detaching it from the device. The gas bubble can be generated in a controlled manner (e.g., slowly) or of a controlled size. The gas bubbles can be generated one at a time. Once formed, the gas bubble can be removed from the device onto a surface, such as retinal tissue or other body tissue. The surface can be that of a biological object, including, but not limited to, the eye, retina, sclera, conjunctiva, hand, skin, or another body part.

[0132] FIG. 24 illustrates one example of a device 640 that can have a handle or housing 641, an elongated knob 648, a rod 650, a flexible loop 652 that can be configured to support a film of bioadhesive material 654, and two or more guide ridges 660 that can be used to guide the loop 652 through an opening 657 at the distal end of the device. The loop can be a retractable loop that can be advanced from the distal end of the device, as shown in FIG. 25. When the loop 652 is within the housing 641, a substance can be applied to the loop 652 through an injection port, via the distal end of the device, through a passageway in the housing, and / or using any of the other devices, components, or methods for advancing a substance through a cannula disclosed herein or known in the industry. Substances can also be added to the loop when it is positioned outside the cannula.

[0133] 25A illustrates another example configuration of a device 670 that can include a handle or housing 672, a rod 674, a cannula 676, and a flexible loop 678 that can be configured to support a film of bioadhesive substance 680 over the loop 678. The cannula may be removable or non-removable. Additionally, the loop 678 can optionally be detached from the rod 674, such that the loop can remain in place after applying the substance to the target tissue surface. Alternatively, the loop 678 can be retracted into the cannula 676, releasing the substance 680, which can be in the form of a bubble or a planar film, from the loop 678. It should be noted that rod 674 may optionally extend from or proximal to the handle portion, such that a user can grasp and manipulate proximal end 674a of rod 674 to advance and retract rod 674 distally and proximally, respectively, rotate rod 674 to manipulate rod and loop 678, etc. In some configurations, the rod may be roughened or indexed into the cannula to prevent rotation of the rod relative to the cannula. The loop material in any of the embodiments described herein may include nitinol, stainless steel, nylon, or any other desired polymeric or other acceptable material.

[0134] Additionally, in some configurations, a desired substance can be applied to the loop 678, and the loop can be retracted into the cannula 676, before the device is delivered to the surgeon or operating room. FIG. 25B shows the device 670 with the rod 674, and thus the flexible loop 678, retracted proximally relative to the handle 672, so that the flexible loop 678 is at least partially (or, as shown, completely) disposed within the cannula 676. For example, but not by way of limitation, as shown in FIG. 25B, the loop can be preloaded with any of a range of desired substances 680, and the loop 678 can be retracted into the cannula. A plug or seal may be placed on or within the cannula to prevent inadvertent release or leakage of the substance from the device. In this preloaded state, the device 670 is ready for use, and the surgeon or user does not need to load the desired substance onto the loop 678. The seal can be removed, and the rod 674 and loop 678 can be advanced beyond the distal end of the cannula once the device is advanced to the desired location, and the substance can be deposited from the loop onto the target tissue or surface.

[0135] Any configuration of rod disclosed herein (including, but not limited to, rod 612, rod 650, and / or rod 674) may be hollow or may be surrounded by an additional sleeve, thereby providing an additional lumen (hereinafter referred to as a supply lumen) through which a further or first supply of substance can be advanced into the loop. For example, without limitation, in some configurations, loop 678 (or any loop disclosed herein) can be drawn into a cannula, and the supply of substance can be advanced through the supply lumen and onto loop 678, past distal end 674b of rod 674 (or any rod disclosed herein), while the loop is positioned within the cannula. This can result in the loop being loaded and / or reloaded with the substance within the cannula, with the loop and the substance advanced through the supply lumen being confined within the cannula, preventing inadvertent contact of the substance with any unintended surfaces. Some configurations of the system and / or device may include a transscleral tip. For example, without limitation, FIG. 26 illustrates one example of a cannula tip portion 690 configuration for administering a substance, the device having, among other features, a cannula or body portion 691 and a transscleral tip 692. The device 690 can also have a first sharp, pointed distal tip 692, which may be beveled or otherwise configured. The tip 692 can be configured to facilitate penetration of the sclera. The device 690 can also have a distal port 696 that can be used to deliver the substance to a desired tissue surface. The port 696 can optionally include a rounded or smooth edge or bevel (chamfer) 698 around the distal port 696. The port 696 may include a silicone-based diaphragm having any of the components and / or characteristics of the diaphragm(s) disclosed above, or a diaphragm made from another material. The end face or tip portion 692 may be solid, may be tapered on both sides or only one side, and may have a conical or other shape.In some configurations, the distal tip 692 can be sharp and can be used to cut ocular tissue. The cannula tip 690 and its features can be used with any of the configurations of the devices disclosed herein.

[0136] Some configurations of the system and / or device can include a tip plug. Non-limiting examples of tip plugs are shown in FIGS. 27 and 28. Tip plugs 700, 720 shown in FIGS. 27 and 28 can include neck portions 702, 722, respectively. The neck portions 702, 722 can be shaped to fit the dimensions of the tip of the cannula. For example, the neck portions 702, 722 can be shaped to fit the dimensions of any material-retaining rim, lip, or ring at the end or tip of the cannula. The neck portions 702, 722 of the tip plugs 700, 720 can include a beveled portion configured to be flush with (overlap) the beveled portion of the distal tip. The tip plug can include a beveled portion configured to be flush with the beveled portion of the distal tip when the elongated member of the tip plug is positioned within the distal tip.

[0137] The tip plugs 700, 720 can include elongated portions 703, 723, respectively. The elongated portions 703, 723 of each plug can be connected to the necks 702, 722 of each plug. The elongated portions 703, 723 can include a proximal end and a distal end. The proximal ends of the elongated portions 703, 723 can be configured to fit within the distal tip of any of the configurations of cannulas or devices disclosed herein. For example, the elongated portions 703, 723 can fit inside a central tube of the system or device. The tip plug can include an elongated member with a proximal end and a distal end, where the proximal end of the elongated member can be configured to fit securely within the distal tip (e.g., to prevent leakage of inflation media). The elongated portion 703, 723 may optionally be 1-5 mm, 5-10 mm, 10-20 mm, 20-30 mm, 30-40 mm, or 40-50 mm in length. For example, the elongated portion may be formed in a range of lengths, as shown in Figure 28. The elongated member 1305, 1405 may include an elongated plug tip that fits inside a central tube of the device or system or at the distal tip of the system or device.

[0138] The tip plugs 700, 720 can include tip plug handles or pull tabs 704, 724. The tip plug handles 704, 724 can be connected to the distal ends of the elongated members 703, 723 or to the necks 702, 722. For example, the tip plugs 700, 720 can include fingertip tabs 704, 724 that are wider and easier to grip compared to the elongated members 703, 723. The fingertip tabs 704, 724 can include a textured surface on one or more sides, such as ridges, dots, and / or hashes, or some other non-smooth surface. The tip plugs can include tabs connected to the distal ends of the elongated members of the tip plugs.

[0139] Referring to FIG. 28 , the tip plug can include one or more support struts 726. The support struts 726 can be configured to prevent the tip plug 720 from breaking when the elongated member 723 is inserted into the distal tip. The support struts 726 are configured to fit around the distal tip and can have a continuous, annular shape or two or more separate struts. Some configurations include a single circumferential support strut. The circumferential support strut can be an outer tube that fits over or around a portion of the tip of the cannula. The tip plug can include an outer tube that fits over or around a portion of the tip of the cannula. The elongated member 723 can be configured to fit inside the cannula. The central core can be longer, shorter, or the same length as the outer tube or support struts 726. Some configurations include a continuous, annular strut. Some configurations include discontinuous struts.

[0140] As described above, some configurations of the system and / or device include a tip cover, such as a protective tip cover. A non-limiting example of another type of tip cover 730 that can be configured for use with any of the cannulas disclosed herein is shown in FIG. 29 . The tip cover 730 can include a first or proximal side and a second or distal side. The first side can optionally include an adhesive configured to engage the cannula. The protective tip cover can further include a non-adhesive tab, such as, for example, but not limited to, the non-adhesive tab 732 shown in FIG. 29 . The tab 732 can be configured to aid in removing the tip cover 730 from the distal tip of the cannula. The tip cover can be removable when the system or device, or the distal tip of the system or device, is ready for use. The cannula can be configured to be filled with or contacted with a bioadhesive substance through the hub of the cannula or through the tip of the cannula prior to securing any of the tip covers disclosed herein.

[0141] The tip plugs or tip covers disclosed herein can be configured to protect the distal tip, maintain the sterility of the distal tip, or prevent the distal tip from contaminating or cutting another object, such as a fingertip or other object, and / or prevent leakage of a substance contained within the cannula or device. For example, a tip plug or tip cover can be attached to the system or device during shipping of the device or system. The system or device can be pre-loaded with a substance, such as a bioadhesive substance. The pre-loaded system or device can include a tip plug or tip cover. The tip plug or tip cover retains the bioadhesive substance within the pre-loaded system or device.

[0142] Any device or configuration disclosed herein can include one or more features configured to disengage material from the device. Such features can include, for example, but are not limited to, cutting features or components such as a razor blade or sharp blade, a thin metal or polymer blade, a scraper, a spatula, or other similar device configured to slide the material off the device. Additionally, in some configurations, air bubbles can optionally be pinched or pinched off the device.

[0143] Any configuration of the systems and / or devices disclosed herein can include an internal ablation component. Some configurations can be configured to have a cannula with a fiber or wire that can be used for light or ablation. FIG. 30 shows an example of a cannula 750 configuration with a fiber or wire for light or ablation. The cannula 750 can include an optical fiber 752 within a lumen along the length of the cannula. The optical fiber 752 can include a curved end 754 in this example, although in other configurations, the end of the optical fiber 752 can be straight. The end 754 of the optical fiber 752 can be beveled at an angle that matches the angle of the bevel at the distal tip.

[0144] Cannula 750 can include light 756 emitted by cannula 758 or end 758 of optical fiber 752. Any configuration of a device disclosed herein can be configured to include one or more optical fibers 752 or any other feature of cannula 750, and cannula 750 can be configured to include any feature of any other cannula, device, or other component or system disclosed herein.

[0145] Additionally, an additional tube can be included that can be configured to pass an additional material (such as a liquid) that can be expressed as a spray or droplets from the distal tip. For example, the additional material may be used to activate the bioadhesive substance. The device or system, or a component thereof, such as a handle, cannula, distal tip, light, or optical fiber, can be configured to emit light at a wavelength that activates, thickens, or hardens the bioadhesive substance.

[0146] The system and / or device and / or components thereof may be actuated to increase the temperature of the distal tip (e.g., using an internal cauterizing component), which, in some configurations, may be advantageous in aiding in the detachment of bioadhesive gas bubbles from the distal tip, where the bioadhesive substance may be a temperature-responsive material that becomes more flowable and / or less cohesive at higher temperatures.

[0147] Some configurations include a cryotherapy arrangement element, such as a cryotherapy handpiece. The system or device can be activated (e.g., using a cryotherapy component) to reduce the temperature of the distal tip. This can be advantageous in some configurations in that the bioadhesive substance may be a temperature-responsive material that becomes more fluid, brittle, or peelable at lower temperatures, helping to dislodge air bubbles or other forms of matter from the distal tip.

[0148] Some configurations of the systems and / or devices disclosed herein can have specialized ends that can have an increased application area, for example, for applying heat or cold to a tissue surface or bioadhesive. Some configurations can have a distal end with a solid, circular shape, such as a button shape. FIG. 31 shows a first perspective view of an example of an end component 770 having a button-tip configuration, and FIG. 32 shows a second perspective view. The button-tip end component 770 can have an enlarged end face or portion 772 and an elongated arm portion 774 coupled to the end component 772, which can be straight or curved, as shown. The end component 772 can be solid or can have one or more passages therethrough for inflation fluids, substances, or other materials.

[0149] The button base can include a solid floor with an opening for the distal tip that terminates flush with the floor. The surface of the button can be open to form a reservoir configured to hold a substance, such as a bioadhesive substance. The surface of the button can be solid with a central opening. The distal surface 776 of the end 772 can be generally flat, curved, or otherwise configured.

[0150] The button tip cannula can be configured to be heated or cooled and can be used to liquefy viscous, solidified, or partially solidified bioadhesive by holding the cooled or heated button tip cannula over the bioadhesive material until it can be converted to a liquid state that allows it to be aspirated with the same or a different device. This button tip design provides a large area of ​​either heat or cold over a large area of ​​bioadhesive, resulting in more rapid liquefaction and removal of the bioadhesive than can be achieved with a cooling or heating tip having a smaller surface area.

[0151] Examples of substances that may 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 treatment substances, bilayer hydrogels, non-solids, etc. As used herein, any use of the term substance is intended to include any of the types and examples of substances disclosed anywhere in this disclosure.

[0152] Examples of substances that may be used with any of the devices, systems, and methods disclosed herein and are considered to be included within each use of the term "substance" herein include, but are not limited to, any of adhesives, bioadhesives, gels, hydrogels, thickened liquid or semi-liquid handling substances, bilayer hydrogels, non-solids, polyethylene glycol solutions, trilysine amine solutions, polymer hydrogels, thermoresponsive gels, polyvinyl acetate, glues, aliphatic, cyanoacrylate-based materials, epoxies, polyurethane adhesives, and contact cements, glycoproteins, elastomeric proteins, carbohydrates, mucopolysaccharides, hydrogels, bilayer hydrogels, polymer hydrogels, polyethylene glycol hydrogels and other hydrogels, biomimetic materials, ReSure™ sealant, polyethylene glycol hydrogels, fibrin glues, polyethylene glycol solutions, trilysine amine solutions, glycoproteins, polyethylene glycol solutions, trilysine amine solutions, elastomeric proteins, carbohydrates, mucopolysaccharides, temperature-activated bioadhesives, UV-activated or light-activated bioadhesives, and vaccines.

[0153] Any of the configurations disclosed herein can also be configured to use one or more substances that polymerize as the temperature of the substance reaches a threshold or range of values, such as, but not limited to, normal body temperature, or about 80°F (about 26.7°C) to about 100°F (about 37.8°C) or higher, or about 90°F (about 32.2°C) to about 100°F (about 37.8°C) or higher, or about 95°F (about 35°C) to about 100°F (about 37.8°C) or higher, or any value within these ranges. Additionally, any arrangement can be used to apply a cold-setting substance to the tissue surface, i.e., a substance that polymerizes as the temperature of the substance drops to a threshold or range of values, for example, but not limited to, 10°F (about -12.2°C) below body temperature, or from about 70°F (about 21.1°C) or below to about 90°F (about 32.2°C), or from about 80°F (about 26.7°C) to about 90°F (about 32.2°C), or any value within these ranges.

[0154] Any of the configurations disclosed herein can also be configured to use one or more substances that polymerize or are activated by light of any number of different wavelengths. The activating light may be provided by a specialized applicator within the substance delivery device or separate from the substance delivery device. Suitable substances that can be used include substances typically used or approved for use on the ocular surface, including the subretinal space, vitreous cavity, or epiconjunctival or subconjunctival spaces, as well as substances that may be used to close gaps in tissue.

[0155] The materials can be configured to be ophthalmically safe and non-toxic, injectable, and capable of bonding to retinal tissue when hydrated and / or hardened. The materials can also include materials with favorable bubble / foam forming properties, including, but not limited to, adhesive and non-adhesive materials for use both inside and outside the eye or any other human or animal tissue.

[0156] After creation of the bioadhesive bubble and dissociation of the bioadhesive bubble from the distal tip, the bioadhesive material may be activated with the application of a solution that may be delivered by a bioadhesive delivery device, which may be constructed so that it has separate tubes for delivery of the bioadhesive material and the activation solution.

[0157] The devices disclosed herein may be used for vaccine delivery, and the substance delivered by the device may include a vaccine. Vaccine delivery may include nasal delivery using air bubbles, which may be more efficient than spray delivery. The devices may deliver vaccines at higher concentrations over a larger surface area than existing vaccine delivery methods, potentially increasing the amount of vaccine absorbed by the subject to which the vaccine is administered.

[0158] Other substances that can be delivered using any of the configurations disclosed herein and are contemplated as part of the term substance as used herein include substances that polymerize as they approach body temperature, substances that are activated to polymerize by any number of different wavelengths of light, light-activated substances, and substances intended for use on the ocular surface, including the subretinal space, the vitreous cavity, or on or under the conjunctiva.

[0159] Any combination of the devices and / or components described herein can be provided together in a kit. Some configurations of the kit further include a second system or device, each disposable after a single or limited number of uses. Some configurations of the kit further include an adhesive biomaterial. Some configurations of the kit further include a substance dispenser. Some configurations of the kit further include a tip plug or protective cover. The described systems, devices, or kits may be sterilized or pre-sterilized. The kit may include a pre-sterilized substance dispenser described herein. The device can be used for delivery of non-medical substances, including, but not limited to, adhesives, lubricants, insulators, and sealants (e.g., gas fittings or pipe / plumbing fittings). This may be preferable to Teflon tape in hard-to-reach areas.

[0160] The system and / or device configuration can include a substance dispenser. The substance dispenser can include a base having a well or a series of wells or an open-ended reservoir. The dispenser can include a container made of plastic, metal, or glass. Each well or series of wells can contain a substance, such as a bioadhesive substance. Alternatively, the substance dispenser can include a series of distal tips pre-loaded with a substance configured to be selectively attached to a handpiece or cannula of any configuration disclosed herein. The cannula(s) can be configured for single or single use, or can be reusable. For example, the cannula can optionally be configured to be reusable within a period of time, such as 1 to 60 minutes, 1 to 24 hours, and / or 1 to 3 days.

[0161] An example of a substance dispenser 790 is shown in Figures 33 and 34. This example can include a base 792 having a series of wells or reservoirs 793, each containing or pre-loaded with a bioadhesive substance, or each containing a different cannula or tip portion. Each well can optionally contain a single dose of substance or multiple doses of substance. The diameter of each well can be such that a cannula can fit securely within the well so that the substance can be efficiently and cleanly drawn into the cannula. In some configurations, the substance dispenser 790 can have multiple cannulae that can be detached from the base 792 and attached to the device being used.

[0162] Some configurations of the system and / or device include a method of using a substance dispenser. The method can include placing a cannula into a well containing a dose of substance, and / or optionally applying a small amount of gentle suction to the cannula to engage the substance within the tip of the cannula, and withdrawing the cannula from the dispenser. Each well of the substance dispenser can include a tear-off cap or cover. The substance dispenser can be sterilized or pre-sterilized and / or contain a sterile liquid or substance, such as a sterile bioadhesive substance.

[0163] 35 is a cross-sectional view of a distal tip 800 having first and second material delivery channels through at least a portion of the distal tip. An attachment or coupling 801 can be formed between an inner tube or channel 802 and an outer tube or channel 804. This attachment can be along the entire length of the channels or can have intermittent attachments.

[0164] The distal tip 800 can have a space 808 between the inner tube 802 and the outer tube 804. The distal tip 800 can also have a material retention rim 810 extending radially inward adjacent a distal end port or opening 812 of the distal tip 800. The space provided inside the retention rim 810 can be filled with a material to aid in bubble formation. The example of FIG. 36 shows the attachment 30 between the inner tube 802 and the outer tube 804. In some configurations, a connector can be used to stabilize the inner tube 802 within the outer tube 804.

[0165] Another configuration of this device is shown in FIG. 37. A first reservoir 812 (or first substance delivery channel) and a second reservoir 814 (or second substance delivery channel) can be formed along the length of the distal tip 800. The first and second reservoirs can be divided and separated along their length. In the example shown in FIG. 37, the first reservoir can be configured to hold a first substance, and the second reservoir can be configured to remain empty and act as a receptacle for (or receive) a second substance or activation solution as it advances from the end of the first reservoir. A distal tip plug may be used to prevent spillage of the substance from the distal tip. The first and second reservoirs may each be configured to hold a separate bioadhesive substance or activating substance, and / or the two reservoirs may be configured to release both bioadhesive substances together, allowing the bioadhesive substances to mix and optionally react with each other before forming a film and bubbles.

[0166] Any of the devices disclosed herein can be used to apply a bioadhesive bubble to the retina and include a proximal end with a handle, a distal end, an internal fluid passageway from the proximal end to the distal end, and a cannula connected to the distal end, the distal end having a distal tip, the device configured to generate a bioadhesive bubble from the bioadhesive when gas flows through the internal fluid passageway, maintain the bubble on the distal tip when gas stops flowing through the internal fluid passageway, and release the bubble when it can rub against the retina or when gas flows again through the internal fluid passageway.

[0167] Some configurations relate to the use of a system, device, or kit for generating and / or applying a bioadhesive bubble to the eye or retina, such as for eye or retinal repair, which can include using a system, device, or kit described herein to generate a bioadhesive bubble and / or using a system, device, or kit described herein to apply a bioadhesive bubble from the tip of a cannula to the eye or retina.

[0168] Some configurations relate to methods of repairing retinal breaks. Some configurations of the methods or uses include using a system, device, or kit to generate a bioadhesive bubble comprising a substantially spherical film of bioadhesive material that encapsulates an inflation fluid. Some configurations of the methods or uses include applying the bioadhesive bubble to the eye or retina from the system, device, or kit. Some configurations relate to methods of repairing retinal breaks or holes, comprising using a system, device, or kit to generate a bioadhesive bubble comprising a substantially spherical film of bioadhesive material that encapsulates an inflation fluid, and applying the bioadhesive bubble to the eye or retina from the system, device, or kit. Some configurations involve operating a button on a handpiece of the device or system, or operating a foot pedal, for example, to open a valve to allow inflation fluid to flow through the inflation fluid passageway of the handpiece and / or through the fluid passageway of the cannula.

[0169] Some of the devices disclosed herein convert cohesive liquids into bubbles that have a much larger surface area and greater control and precision of placement than the original, bubble-free cohesive liquid, significantly improving their ability to close gaps in tissue and to reduce the incidence of PVR by blocking the release of RPE cells into the vitreous cavity when used for either function.

[0170] The devices and methods disclosed herein can be used to close a variety of discontinuous and continuous structures, including, but not limited to, retinal breaks and holes, macular holes, macular fossa, posterior lens capsule breaks, scleral tears, corneal lacerations, corneal abrasions, conjunctival tears, retinal pigment epithelial tears, and non-intraocular medical applications, including, but not limited to, skin lacerations, mucosal lacerations (regardless of location), and delivery of substances without other functions, including, but not limited to,

[0171] Any of the devices disclosed herein can be used to deliver substances transvitreally. For transvitreal use, delivery through the device may use a cutting action to sever cohesive / adhesive substances after the substance has advanced to the target location. Excess may be removable with a vitrectomy cutter and / or suction. Transvitreous delivery can be utilized in air-filled eyes to avoid spillage of adhesive substances onto non-target ocular structures, such as the lens / IOL / ciliary folds / angle, corneal endothelium, etc., which may obscure vision through the lens / IOL or impede aqueous humor inflow / outflow.

[0172] Any of the devices disclosed herein can also be delivered via transcleral delivery, which may include delivery of a substance to a retinal hole through the subretinal space. After the substance is delivered through the tapered end or needle of the device and applied to the retina, the substance may be released as the needle is withdrawn from the sclera. The substance may act as a buffer to prevent the retina from penetrating into the scleral defect left by the cannula, needle, or device utilized to traverse the scleral and choroidal tissues.

[0173] Any configuration of the delivery device disclosed herein can have a single, dual, or triple bore. A dual-bore device can include one bore for delivering a substance and a second bore for refluxing intraocular fluids outside the eye as IOP (intraocular pressure) increases. One of the bores can include an optical fiber, which may be used for illumination. One of the bores contains a fiber capable of delivering laser light. One of the bores contains a fiber for delivering heat or some other energy source used to harden the injected substance. A triple-bore device can include one bore for delivering a substance, one bore for passing gas used to create a bubble or film of adhesive substance, and a third bore for refluxing intraocular fluids outside the eye as IOP increases.

[0174] 38-42 show schematic diagrams of example distal ends or tips of various configurations 900, 910 of the device. In any configuration, a single-compartment syringe or a dual-compartment syringe can be attached to the distal tip, and the dual compartments fit together when connected. With reference to FIGS. 40 and 41, dual isolated columns of air can optionally compress the contents within the two distal tip sections 912, 914. Some configurations include a handle, such as a syringe-like handle.

[0175] As shown in Figures 38-42, there may be an internal aspect of the distal tip, which may be flared to provide support and stability to the tip bubble. The tip may contain an outer hollow wall, a material such as air or gas within the interior or interior surface. The tip may have one or more openings (e.g., passageways) that can communicate between the hollow wall of the cannula-containing material and the central core of the cannula through which a gas, such as air, nitrogen, oxygen, or another gas, can pass. A film of material can be created across the opening at the distal end or distal tip. The hollow wall of the cannula may be of various volumes, and the relative volumes of the hollow wall and central core may vary. Some configurations include dual plungers for the central core and / or the hollow-walled outer cannula. The dual plungers may operate and / or advance simultaneously with or independently of the cannula or other components of the device. The components may be of various lengths, widths, and volumes.

[0176] In any configuration disclosed herein, the device and / or method of use can be configured to have one or more of the following features, characteristics, capabilities, processes, or details: a handheld syringe-shaped device that generates gas bubbles in a controlled manner, one bubble at a time; the ability to generate gas bubbles from liquids of various compositions and viscosities; the ability to generate gas bubbles from gels of various compositions and viscosities; the ability to maintain a reservoir of the substance in which the bubbles are generated at a temperature within a specific range depending on the substance being used; a temperature-controllable chamber within the device that can be specifically calibrated locally for the substance being used in the procedure so that the temperature control can be turned on and off, although a temperature control mechanism could optionally be added to the device; a power source comprising one or more batteries, which may optionally be built into the handheld device; a power source comprising an electrical cord that connects to a vitrectomy machine power supply or an external power source; one or more color-coded devices, each color correlating with a specific substance composition, where different substance compositions can optionally have specific optimal temperatures or temperature ranges for optimizing gas bubble generation; For example, but not limited to, devices configured to allow control and variation of bubble wall thickness based on the temperature of the substance during bubble generation using one or more heaters and / or coolers; devices configured to allow control and variation of bubble wall thickness based on the viscosity of the substance during bubble generation; devices configured to vary bubble wall thickness with varying dimensions of the particular device opening and the amount of air or gas passed through the substance composition during the bubble generation process, such as, but not limited to, a kit or system having multiple different devices, each with a different distal tip opening that produces bubbles of a consistent size / diameter and wall thickness that differs from the other devices in the kit; and another configuration having a device with an adjustable opening and the ability to control the volume of air injected to form bubbles, providing the ability to customize bubble size and bubble wall thickness depending on the clinical setting, for example, in retinal detachment applications with multiple retinal breaks of various sizes, where it may be desirable to use bubbles of various sizes but each with approximately the same bubble wall thickness.

[0177] In any configuration disclosed herein, the device may also be configured to have one or more of the following features, characteristics, capabilities, or details: using one device to close a retinal break and then close a cannulated external scleral opening (i.e., sclerotomy) at the end of the case (in which case the surgeon may wish to obtain a larger bubble wall thickness due to the greater tension associated with a scleral wound compared to a retinal hole); for example, in the range of 0.5 mm to 15 mm (other ranges of bubble diameters are variations in the device to generate bubbles of various sizes having diameters of various sizes (e.g., 0.1 mm to 0.5 mm, 0.5 mm to 1 mm, 1 mm to 2 mm, 2 mm to 5 mm, 5 mm to 10 mm, 10 mm to 25 mm, 25 mm to 50 mm, and 50 mm to 100 mm, or any value therebetween); the ability to release bubbles and generate additional bubbles that can be released in a manner that avoids clogging of the cannula / device tip; a mechanism for releasing bubbles from the cannula / device tip that a mechanism for releasing bubbles, which may include one or more of a heating tip to melt or heat the substance, a cooling tip to break up the substance, and a device having a cutting or wiping mechanism at the tip; a device including an optical fiber used to transmit light used to harden the substance used in the balloon, which may be fixed or movable so as to advance from the tip of the device, which optical fiber may be advanced into the interior of the bubble and be proximate to the portion of the bubble that contacts the retina, sclera, or other target human tissue, and / or the optical fiber may be housed in a different bore of a cannula and used to harden the substance from the outside of the balloon; and a device which may include a cannula and associated distal tip separate from the bubble generating portion, which allows for dripping or spraying of a liquid, gel, or other substance onto the surface of the retina prior to application of the bubbles, the purpose of which may be to deposit a substance of a specific composition that reacts with the bubble substance, causing a change in the consistency of both substances, for example from liquid to solid.

[0178] Any of the configurations of the devices and systems disclosed herein can be used to apply adhesive to biological or non-biological surfaces or objects, including medical scaffolds, patches, covers, implants, or other objects or devices used in medical and non-medical applications. For example, without limitation, FIG. 43 shows a non-limiting example of a system 1000 having a substance delivery device 1001 and an applicator device 1002. The substance delivery device 1001 can include any of the devices, configurations, and / or components disclosed elsewhere herein, including but not limited to devices 100, 200, 250, 350, etc., in any combination, to provide a substance to a surface or object. The substance delivery device 1001 can be advanced through a first introducer cannula or sheath to a desired space or location (e.g., without limitation, an air-filled ocular cavity), and the applicator device 1002 can be advanced through a second introducer cannula or sheath to the ocular cavity. The substance delivery device 1001 can be used to apply a substance, which may include a bioadhesive, to a desired surface of the applicator device 1002 .

[0179] 44 and 45 show top and side views, respectively, of one example of an applicator device 1002 that can be used with any of the devices disclosed herein to deliver a substance to a surface or object. As described, in any configuration, the applicator device can be used to receive a substance on an applicator portion for application to a tissue surface or object, to support an object (such as a patch) by itself, and to deliver the object to a desired location, or for other purposes. For example, without limitation, the applicator device can be configured to support a patch, tissue covering, tissue graft, tissue scaffold, or the like (collectively referred to herein as a patch), and a surgeon or user can use the applicator device 1002 to position and apply the patch to a desired target location. The patch can optionally be pre-loaded with an adhesive (which can be a bioadhesive) or other substance, or the adhesive can be loaded at the surgical site or space using the substance delivery device 1001. Thereafter, once the patch is loaded with a desired amount of adhesive, it can be applied to the desired object or tissue surface. Additionally, without limitation, the applicator device 1002 can be used to hold the patch in a desired application position to allow the adhesive to sufficiently harden or cure and thus bond to the target tissue.

[0180] 43 and 44 , applicator device 1002 can include a cannula or outer sleeve 1003 (also referred to herein as an elongate body or outer sheath), an inner sleeve or rod 1005, which can optionally have a solid cross-section or a lumen or passageway 1007 extending therethrough, and an applicator tip 1006 coupled to inner rod 1005. Outer sleeve 1003 can optionally be configured to provide additional rigidity and maneuverability to at least a portion of inner rod 1005 and applicator tip 1006 to facilitate or improve user control of applicator device 1002 during application of substance 1001.

[0181] The inner rod 1005 can have a proximal end 1005a (not shown) and a distal end 1005b. The passageway 1007, if present, can extend from the proximal end 1005a to the distal end 1005b of the inner rod 1005. As shown, the applicator tip 1006 can be coupled to the distal end 1005b of the inner rod 1005. The proximal end of the inner rod 1005 can be manipulable by a surgeon or device user to advance, retract, rotate, and otherwise move the applicator tip 1006.

[0182] The cannula may optionally be flexible, semi-rigid, or rigid and may be formed from any suitable material, including metal alloys, polymeric materials, or others. The system may optionally be configured without the outer sleeve 1003, in which case the inner rod 1005 and applicator tip 1006 are sufficiently rigid and maneuverable so that the outer sleeve 1003 is not required.

[0183] In any of the configurations disclosed herein, the applicator tip 1006 and / or other positioning elements may be pre-loaded into the cannula or outer sleeve 1003 so that the applicator tip 1006 does not need to be advanced into the proximal end of the cannula 1003 after the cannula 1003 has been advanced to the target location, and so that the size of the applicator device 1002 advanced to the target location is dictated by the size of the cannula 1003 rather than the larger applicator tip 1006, thereby improving maneuverability of the device and reducing the risk of injury to the patient. Optionally, the applicator device 1002 may be configured so that the applicator tip 1006 is advanced into the proximal end of the cannula 1003 after the cannula 1003 has been advanced to the target location. The proximal end of the cannula 1003 may be flared or tapered to facilitate insertion of the applicator portion 1010 of the applicator tip 1006 into the cannula 1003 and / or to facilitate folding (crushing) and / or rolling or rolling up of the applicator portion 1010 for insertion into the cannula 1003.

[0184] As mentioned above, when the applicator tip 1006 is in the first or retracted state (i.e., within the cannula 1005), the distal portion of the applicator device 1002 can have a smaller profile or cross-sectional size that can be defined by the outer sleeve 1003 so that it can be advanced through an opening in a tissue surface with less force required and, consequently, less risk of trauma to the tissue. Some configurations of the applicator device 1002 can be configured so that when the applicator portion 1010 is retracted or deployed within the outer sleeve 1003, the applicator portion 1010 can be biased to assume a curved, curled, folded, or rolled shape to fit within the interior space of the outer sleeve 1003, as best shown in FIG.

[0185] 45, the applicator portion 1010 can be configured such that when the inner rod 1005 and the applicator tip 1006 are all retracted within the outer sleeve 1003 from the second condition to the first or retracted condition, the applicator portion 1010 can be biased or otherwise configured to fold into the more compact or narrower shape or condition described above and shown in FIG. 45 so that the applicator device 1002 can be withdrawn through an opening in tissue with the applicator tip 1006 retracted within the outer sleeve 1003. As shown and described, the applicator portion 1010 can have a width W that is greater than the width of the outer sleeve 1003. Because applicator portion 1010 is configured or biased to move to a more compact profile when retracted into cannula 1003, retracting applicator portion 1010 into outer sleeve 1003 can reduce the size of the distal portion of applicator device 1002 to the size of outer sleeve 1003, thereby reducing trauma to the patient during withdrawal of the device, as shown in FIGURE 45. In any configuration, applicator portion 1010 can be arranged to have any feature or made from any material that allows it to be folded, rolled, compressed, squeezed (crushed), narrowed, or otherwise reduced in width W or size to fit within the outer sleeve when retracted into the outer sleeve.

[0186] The applicator portion 1010 can have or define a first width when the applicator portion 1010 is in a first position (the applicator portion 1010 is contained within the outer sleeve 1003) and a second width when the applicator portion 1010 is in a second position (the applicator tip extends beyond the opening in the distal end 1003a of the outer sleeve 1003). The second width of the applicator portion 1010 can be substantially larger than the first width of the applicator portion 1010. In any configuration disclosed herein, the second width of the applicator portion 1010 can be about 5 times larger than the first width of the applicator portion 1010, or about 2 times (or optionally, about 2 times or less) to about 8 times (or optionally, about 8 times or more) the first width of the applicator portion 1010, or about 3 times to about 6 times larger than the first width of the applicator portion 1010.

[0187] The inner rod 1005 can be advanced relative to the outer sleeve 1003 so that the distal end 1006a of the applicator tip 1006 can extend from the distal end 1003a of the cannula 1003. In any configuration, the applicator tip 1006 can have an elongated portion 1008 and an applicator portion 1010. The elongated portion 1008 of the applicator tip 1006 can optionally have a passageway 1012 extending therethrough from the proximal end 1008a to the distal end 1008b of the elongated portion 1008. The passageway 1012 can be operably in fluid communication with the passageway 1007 (if present) of the inner rod 1005 at the proximal end 1008a of the elongated portion 1008. One or optionally multiple openings 1014 can be optionally formed through the first surface 1011 of the applicator portion 1010, with the openings or orifices 1014 being in fluid communication with the passages 1012. The openings 1014 can be used to communicate a source of suction or negative pressure or positive pressure or airflow to any object proximate to or in contact with the applicator portion 1010. A suction source can be communicated to the openings 1014 via the passages 1007 and 1012, for example, from the proximal end of the device, for example, via a handle coupled to the outer sleeve of the device. For example, suction can be applied through the openings to selectively attract and secure any desired object to the first surface 1011 of the applicator portion 1010, including, but not limited to, air bubbles containing a substance (optionally with gentle suction to avoid bursting the air bubbles), a patch, a tissue covering, a scaffold, or other object. For example, but not by way of limitation, a gentle suction force may be applied through opening 1014 to attract and secure the substance-containing bubble against first surface 1011 of applicator portion 1010 .

[0188] The applicator portion 1010 can then move the gas bubbles to a desired location, for example, a tissue defect within a surgical air space within the eye. The material can be released from the applicator portion 1010 by reducing the suction or negative pressure provided through the openings 1014, by pressing and / or manipulating the applicator portion 1010 against the target surface, and / or optionally by exerting positive pressure, such as a short burst or short positive pressure, through the openings. The supply of positive pressure (e.g., by supplying a positive air flow through one or more openings 1014) can be used to facilitate the release of the gas bubbles.

[0189] In another non-limiting example, negative pressure can be used to selectively secure a patch or any other device against the first surface 1011 of the applicator portion 1010. For example, as shown in FIG. 46 , a suction source can be applied to a patch or other medical device 1025 through the opening 1014 to selectively and releasably hold the patch 1025 against the first surface 1011 of the applicator portion 1010. The patch 1025 can then be delivered to the desired location by advancing the applicator device 1002 to the target location and can be advanced into contact with the target tissue surface. When the desired position of the patch 1025 is achieved and the patch has optionally been held in place long enough to secure it to the target tissue surface, the negative pressure can be reduced and the patch can be released from the applicator portion 1010. Positive pressure or airflow can optionally be provided through the opening to facilitate patch release.

[0190] 46 , a suction source can be applied to a patch or other medical device 1025 through opening 1014 to selectively and releasably hold patch 1025 against first surface 1011 of applicator portion 1010. Thereafter, substance delivery device 1001 (which may be or include any component or detail of a bubble, loop, or other substance delivery device disclosed herein) can provide a layer of bubble 146 or substance 105 on the surface of patch 1025. The substance 105 can be a bioadhesive. The bubble 146 and / or substance 105 can be applied to the patch as described above for device 130 of FIGS. 4A-4D . After substance 105 has been applied to the patch, patch 1025 can be delivered to a desired location, and the adhesive-coated surface of patch 1025 can be advanced into contact with a target tissue surface by advancing applicator device 1002 to the target location, as shown in FIG. 47 . When the desired position of the patch 1025 is achieved and the patch has optionally been held in place long enough to secure it to the target tissue surface, the negative pressure can be reduced, releasing the patch from the applicator portion 1010. In any configuration, the applicator portion 1010 may be biased and configured such that as the applicator portion 1010 is retracted into the cannula 1003, interaction with the distal end of the cannula 1003 causes the applicator portion 1010 to assume a folded or rolled-up shape, thereby allowing the applicator portion 1010 to be fully retracted into the cannula.

[0191] In other configurations, the applicator portion 1010 may be solid and may have no openings or orifices therein. Additionally, the applicator tip 1006 may have a planar shape, a curved shape as shown in FIG. 46 , or other shapes. In other configurations, clips, tabs, indentations, ridges, protrusions, or other features may be used to selectively and releasably retain a patch or other medical device on the first surface 1011 of the applicator portion 1010. In other configurations, the applicator portion 1010 and applicator device 1002 may be configured to allow a patch, cover, or other medical device to rest freely on the first surface 1011 of the applicator portion 1010. In any configuration, the patch can be pre-loaded into the cannula 1002 and can be rolled up against the surface 1011 of the applicator portion 1010, so that as the applicator portion 1010 advances from the distal end of the cannula 1003, the applicator portion 1010 can self-expand or open to an open shape, with the patch 1025 still being held against the first surface 1011 of the applicator portion 1010.

[0192] In an optional configuration, the patch can be secured to the proximal end of the patch using end-grasping forceps extendable from the cannula. The forceps can be self-expanding so that the forceps open and release their grip on the patch as the cannula is retracted relative to the forceps or the forceps are advanced distally relative to the distal end of the cannula. In this configuration, the patch can be pre-loaded inside the distal end of the cannula with at least a portion of the patch grasped by the forceps. Because the forceps are constrained by the cannula, the forceps maintain their grip on the patch until the forceps are advanced distally from the cannula or the cannula is retracted proximally relative to the forceps. For example, as the forceps are advanced distally relative to the cannula, the patch can be moved beyond the distal end of the cannula, allowing it to unfold, unravel, or unfurl into a relaxed, expanded state while still being sufficiently constrained by the cannula in a closed position so that the forceps continue to grip the patch. In this state and position, a substance, such as a bioadhesive, can be applied to the desired surface of the open or relaxed patch using any of the substance applicator devices disclosed herein (e.g., and without limitation, device 130). The substance can be applied as a bubble, multiple bubbles, or otherwise. The substance applicator can also optionally be used to spread the substance over the surface of the patch. After the adhesive has been sufficiently applied to the surface of the patch, the patch can be placed in contact with the desired tissue surface until the substance creates a sufficient bond between the patch and the tissue surface. The forceps can then be further expanded to release their grip on the patch by button or slide operation or otherwise advancing the forceps distally relative to the cannula and / or retracting the cannula to allow the forceps to expand, after which the forceps can be withdrawn back into the cannula and removed from the surgical site.

[0193] The forceps or other grasping means disclosed in any of the configurations herein can be or can include ALCON Revolution DSP forceps or GRIESHABER DSP forceps, for example, such forceps can be used to grasp and / or manipulate patches used in any of the configurations disclosed herein.

[0194] The patch can also be released from the applicator portion by the surgeon or user using any mechanical components, including end-grasping forceps and a button that allows the attached patch and / or patch material to be advanced. If the forceps are loaded in a passive open position, they can be biased or configured to open or return to their open or relaxed state when the forceps are extended beyond the distal tip of the cannula.

[0195] Alternatively, the same inner end-grasping forceps can pinch the patch with its tip, but use the button in the opposite manner to retract the cannula from around the end-grasping forceps and attached patch. This allows the surgeon to hold the tip of the cannula near the target tissue and slowly expose the patch without actually advancing it forward, thereby avoiding impinging the patch on the retina, which can occur if the surgeon does not compensate by gradually pulling the cannula back from the retina as the tip advances. Once the cannula is fully retracted proximal to the tip of the end-grasping forceps, the forceps are biased to passively open and release the patch or spatula, or both.

[0196] Additionally, some configurations can include a selectively severable connector 1022 coupling the proximal end 1008a of the elongate body 1008 to the distal end 1005b of the inner rod 1005. Thus, in some configurations, the applicator tip 1006, including at least the applicator portion 1010, can be released from the inner rod 1005 by disengaging the connector 1022. This allows the applicator tip 1006 to be removed from the device and left in place within the patient. In this configuration, the applicator portion 1010 can essentially be a patch or cover for a defect. The applicator tip 1006 can be made from any suitable material, including any suitable bioabsorbable or biocompatible material.

[0197] In any configuration of the applicator device 1002 or any substance delivery device embodiment disclosed herein, the handle, cannula or outer sheath 1003, inner sheath 1005, or other rigid or semi-rigid components can be made from or include any suitable plastic material, patch material, metal, polyvinyl chloride, glass, acrylic material, carbon fiber, and / or any combination thereof. In some configurations, the cannula tip plug or protective tip cover can include plastic, metal, polyvinyl chloride, glass, acrylic material, carbon fiber, rubber (such as, but not limited to, silicone), and / or any combination thereof.

[0198] While 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 such forms or modifications that fall within the scope and spirit of the present disclosure. Accordingly, the scope of the present invention is defined solely by reference to the appended claims.

[0199] It should be understood that features, materials, properties, or groups described in connection with a particular aspect, embodiment, or example may also be applied to any other aspect, embodiment, or example described in this section or elsewhere in this specification, to the extent compatible. All features disclosed in this specification (including any 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 the foregoing embodiments. Protection extends to any novel one or any novel combination of features disclosed in this specification (including any accompanying claims, abstract, and drawings), or any novel one or any novel combination of steps of any method or process so disclosed.

[0200] Furthermore, certain features that are described in this disclosure in the context of separate embodiments can also be implemented in combination in a single embodiment. Conversely, various features that are described in the context of a single embodiment can also be implemented in multiple embodiments separately or in any suitable subcombination. Furthermore, while features may be described above as acting in a particular combination, one or more features from a claimed combination may, in some cases, be deleted from that combination, and the combination may be claimed as a subcombination or a variation of the subcombination.

[0201] Furthermore, while operations may be depicted in the figures or described in the specification in a particular order, such operations need not be performed in the particular order shown, or in any sequential order, or even all of the operations need to be performed to achieve desired results. Other operations not shown or described may be incorporated into the example methods and processes. For example, one or more additional operations may be performed before, after, simultaneously with, or during any of the described operations. Furthermore, operations may be rearranged or resequenced in other embodiments. Those skilled in the art will appreciate that in some embodiments, the actual steps taken in the illustrated and / or disclosed processes may differ from those shown in the figures. Depending on the embodiment, some of the above-described steps may be removed, and other steps may be added. Furthermore, the features and attributes of the specific embodiments disclosed above may be combined in different ways to form additional embodiments, all of which are within the scope of the present disclosure. Also, the separation of various system components in the above-described embodiments should not be construed as requiring such separation in all embodiments, and it should be understood that the described components and systems may generally be integrated together in a single entity or packaged in multiple entities.

[0202] For purposes of this disclosure, certain aspects, advantages, and novel features have been described herein. Not necessarily all such advantages may be achieved in accordance with any particular embodiment. Thus, for example, one skilled in the art will recognize that the present disclosure may be embodied or carried out in a manner that achieves one advantage or group of advantages as taught herein, without necessarily achieving other advantages that may be taught or suggested herein.

[0203] Conditional terms such as "can," "could," or "may," unless otherwise specified or understood otherwise in the context in which they are used, are generally intended to convey that certain embodiments include certain features, elements, and / or steps, while other embodiments do not. Thus, such conditional terms are generally not intended to imply that features, elements, and / or steps are somehow required in one or more embodiments, or that one or more embodiments necessarily include logic for determining whether those features, elements, and / or steps are included in or should be performed in any particular embodiment, with or without user input or prompting.

[0204] Connected language such as the phrase "at least one of X, Y, and Z" is generally understood to convey that, unless otherwise indicated, apart from the context in which it is used, an item, term, etc. may be either X, Y, or Z. Thus, such connective language is generally not intended to imply that a particular embodiment requires the presence of at least one of X, at least one of Y, and at least one of Z.

[0205] As used herein, terms of degree, such as "approximately," "about," "generally," and "substantially," refer to a value, amount, or characteristic that is close to a stated value, amount, or characteristic that still performs a desired function or achieves a desired result. For example, the terms "approximately," "about," "generally," and "substantially" can refer to an amount that is within less than 10%, less than 5%, less than 1%, less than 0.1%, and less than 0.01% of the 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 exactly parallel by 15 degrees or less, 10 degrees or less, 5 degrees or less, 3 degrees or less, 1 degree or less, or 0.1 degrees or less.

[0206] The scope of the present disclosure is not intended to be limited by the specific disclosure of preferred embodiments in this section or elsewhere herein, but may be defined by the claims presented in this section or elsewhere herein or presented in the future. Claim language is to be interpreted broadly based on the language employed therein and not limited to the examples described herein or during the prosecution of this application, which examples are to be construed as non-exclusive.

Claims

1. 1. An applicator device (1002) for applying a bioadhesive substance to a retina, comprising: The applicator device comprises a sleeve having a proximal end, a distal end, and a passageway extending along the length of the sleeve (1003) from the proximal end to the distal end of the sleeve (1003), an elongate body (1005), and an applicator tip (1006) coupled to the distal end of the elongate body (1005) movable within the sleeve (1003); an applicator portion (1010) of the applicator tip (1006) curves along the inner circumference of the sleeve (1003) so as to fit into the internal space of the sleeve (1003) in a first folded state retracted into the sleeve (1003); the applicator portion (1010) of the applicator tip (1006) is self-expandable from the first collapsed state to a second expanded state upon exiting the distal end of the sleeve, the applicator portion (1010) having a width (w) in the second expanded state that is greater than the width in the first collapsed state; The applicator device (1002) is configured so that the bioadhesive substance is transferred from a substance source to the applicator tip (1006) of the applicator device (1002) and from the applicator tip (1006) of the applicator device to a tissue surface having a defect.

2. 2. The applicator device of claim 1, further comprising a patch (1025) removably supported on the surface of the applicator tip (1006), the patch (1025) being supported so that the bioadhesive substance can be transferred from the substance source to the patch (1025) supported by the applicator tip (1006) of the applicator device, and so that the patch (1025) can be transferred from the applicator tip (1006) of the applicator device to the tissue surface having the defect.

3. The applicator device of claim 1 or 2, wherein the applicator device (1002) is configured to transfer the substance as a bubble or a thin film.

4. An applicator device according to any preceding claim, wherein the inner sleeve (1005) has a lumen or passageway (1007) extending therethrough.

5. 5. The applicator device of claim 4, wherein the applicator tip (1006) comprises an elongated portion (1008) and the applicator portion (1010), the elongated portion (1008) of the applicator tip (1006) having an applicator tip passage (1012) extending through the elongated portion (1008) from its proximal end to its distal end, and the applicator tip passage (1012), when in an operable state, is fluidly connected to the passage (1007) of the inner sleeve (1005) at the proximal end of the elongated portion (1008).

6. 6. The applicator device of claim 5, wherein one or more openings (1014) are formed through a first surface (1011) of the applicator portion (1010), the openings (1014) being in fluid communication with the applicator tip passage (1012).

7. An applicator device according to any one of claims 4 to 6, wherein the applicator portion (1010) is configured to fold into a more compact or narrower shape when the inner sleeve (1005) and the applicator tip (1006) are retracted within the sleeve (1003) from the second expanded state to the first folded state, thereby allowing the applicator portion (1010) to be withdrawn through an opening in tissue with the applicator tip (1006) retracted within the sleeve (1003).

8. 8. An applicator device according to any one of claims 1 to 7, wherein the applicator portion (1010) has a first width when the applicator portion (1010) is in the first folded state and a larger width (w) when the applicator portion (1010) is in the second expanded state, the larger width being from about 2 to about 8 times the first width, or from about 3 to about 6 times the first width.

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