Devices and methods for targeted delivery of substances

Abstract

Devices, systems, and methods for applying a bioadhesive material to the inner surface of an eye, such as the retina, can include an outer sleeve having a proximal end, a distal end, a passage extending along the length of an elongated body, and an opening at the distal end of the elongated body, an applicator tip including an elongated body having a proximal end and a distal end, an applicator portion coupled to the distal end of the elongated body, and a material supply conduit extending along the length of the device through which the bioadhesive material can pass such that the bioadhesive material can be applied to at least the applicator portion of the applicator tip. Some embodiments of the device can also have a source of bioadhesive material in fluid communication with at least the material supply conduit.

Description

Background Art

[0001] This application claims the benefit and priority of U.S. Provisional Patent Application No. 17 / 946,644, filed Sep. 16, 2022, which claims priority as a continuation-in-part of U.S. Non-Provisional Patent Application No. 17 / 866,111, filed Jul. 15, 2022. The entire contents of each of these priority applications are incorporated herein by reference as if fully set forth herein for all purposes.

[0002] Existing methods for fixing macular holes and retinal detachments associated with discontinuities in the retina, such as tears and holes, include the use of perfluorocarbons, lasers, cryotherapy, bubble injection, and silicone oil. Using perfluorocarbons for the movement of fluid from the subretinal space can result in inadvertent movement of the perfluorocarbon liquid into the subretinal space, which can cause vision loss if it is located in the central macula. Incomplete removal of the perfluorocarbon liquid from the vitreous cavity can result in related visual phenomena that the patient may find uncomfortable. The use of lasers and cryotherapy results in the formation of permanent retinal scar tissue and can contribute to the formation of epiretinal membranes and supraretinal scar tissue. The use of bubble injection results in restrictions on the patient's activities and can cause complications such as increased intraocular pressure and cataracts. Similarly, silicone oil can cause complications such as increased eye pressure, requires a second surgery for removal, and the oil bubbles frequently remain after attempted removal, which can be problematic as the patient may become visually confused.

[0003] Existing methods for fixing leaky ocular wall discontinuities, such as incisions, sclerotomies, and lacerations, include sutures and commercially available bioadhesives. Leakage may continue from the sutured discontinuity. Sutures cause a local tissue reaction including irritation, pain, tearing, and sometimes, edema and inflammation of the episclera and conjunctiva.

Summary of the Invention

Problems to be Solved by the Invention

[0004] One drawback of some bioadhesives is that they can induce toxicity. Another drawback is that it can be difficult to apply a bioadhesive to the non-dependent ocular surface both inside and outside the eye due to the influence of gravity on the bioadhesive and other factors when the bioadhesive leaves the tip of the bioadhesive delivery device. For example, in an eye with a retinal tear on the side or top of the eye, gravity can cause the bioadhesive to drip or sag as soon as it is discharged from the applicator device, which may prevent accurate application of the bioadhesive onto the discontinuity of the retina, so gravity can make it difficult to apply the bioadhesive to the retinal tear. The same problem occurs when attempting to apply a liquid or viscous material to the lateral and inferior outer ocular surface. Another drawback of bioadhesives is that they can be difficult to apply to large discontinuities of the retina and other ocular surfaces, as well as to tissue discontinuities with irregularly shaped edges and edges at different heights from each other. The challenge of applying a bioadhesive to a retinal discontinuity can be even more difficult when attempting using a transscleral subretinal approach.

Means for Solving the Problem

[0005] The configurations disclosed herein optionally include devices, systems, and methods for applying a substance, such as a bioadhesive, to the surface of an object. The tissue can be biological or non-biological (e.g., non-viable) tissue and can include medical scaffolds, patches, covers, grafts, or other objects used for medical and non-medical applications. The object can be a tissue such that the devices and methods disclosed herein apply the substance to the tissue surface. The tissue can be damaged tissue of any of the types or uses disclosed herein, including but not limited to retinal tissue or other ocular tissue. As used herein, any feature, component, or other detail described with respect to a component, device, system, method, or any configuration thereof is meant to apply to any of the other similar or suitable components, devices, systems, methods, and their configurations disclosed herein.

[0006] As described below, the devices, systems, and methods disclosed herein are configured to optionally apply a substance that can be a bioadhesive to a target tissue as a bubble, thin film, or other similar shape or configuration. Some non-limiting examples of any use of any of the devices and methods disclosed herein include applying a biological substance, such as a bioadhesive, to eye tissue (e.g., retinal tears, retinal holes, retinal detachments, etc.), applying a bioadhesive to the sclera, conjunctiva, and cornea, applying a biological substance, such as a bioadhesive, to gastrointestinal tissue, colon tissue, etc. to seal perforations or tears therein, air-filled eye cavities or spaces, etc. However, the configurations of the devices and methods disclosed herein are not limited to the delivery of therapeutic substances or to ophthalmic, medical, or biological uses. Any of the devices and methods disclosed herein can be used for the delivery of any desired or suitable substance or material in any biological, non-biological, mechanical, or other desired use.

[0007] Any configuration of a device for applying a substance to a tissue can optionally comprise 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 passage (also referred to herein as a first passage) in fluid communication with the outlet port. The fluid passage can extend from the handle towards the intermediate region or beyond the distal end. The elongate body can also include a tube member or cannula that can have a proximal portion, a distal tip, and a body portion extending therebetween.

[0008] In any configuration, the system can include, comprise, or be constituted from a single device in which all components of the system are connected (e.g., fluidly coupled) to each other. Further, in any configuration, the system can include, comprise, or be constituted from non-single devices in which one or more components of the system can be removed from or made removable from another component of the system, or can be provided completely separately from other components. Some configurations of the devices can be modular and interchangeable components.

[0009] Various materials can be used to fabricate 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.

[0010] The distal tip and / or the end face of the distal tip in any configuration disclosed herein can have a retaining ridge, lip, or rim with a flat surface configured to hold and maintain a foamy substance. The end face of any device disclosed herein can have an inner member that faces circumferentially inward toward the center of the distal tip or extends circumferentially within the cannula outlet port. The inner member can be configured to hold a bioadhesive substance and assist in the formation of a bioadhesive foam or a spherical film of the bioadhesive substance. The distal tip can have a plurality of end faces. In some configurations, the distal tip can have only one end face. The distal tip can be obtuse or rounded, or can have an obtuse or rounded end.

[0011] The distal tip of any configuration can optionally have a peripheral portion and four or more, or two to eight, or four to six flaps that extend inwardly across the cannula exit port. One or more flaps can have an angled edge. The flaps can be manufactured using a variety of materials including, but not limited to, rubber, silicone, plastic, or elastomeric materials.

[0012] Some configurations of the system further comprise a substance supply channel within the device or advanced into the device to assist in the generation of bioadhesive bubbles. The substance supply channel may be inside or outside the inflation fluid passage of the device (sometimes referred to herein as the handpiece) and / or the fluid passage of the cannula. The substance supply channel can have an elongated body with a proximal end and a distal end including a substance supply tip and / or an outlet port. The substance supply channel can be inside or surrounded by at least a portion of the inflation fluid passage of the cannula body and / or the fluid passage of the cannula base or tip. The cannula can have an outer wall and an inner wall, the inner wall can optionally provide a boundary to the substance supply channel, and the space between the inner wall and the outer wall comprises 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 substance supply tip can have a surface inclined compared to the longitudinal axis of the substance supply channel body and the substance supply outlet port. The end face of the substance supply tip can have an angle 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° compared to the longitudinal axis of the substance supply channel body, or an angle within a range including two or more of the aforementioned angle ranges. The substance supply channel can have a substance supply tip having one, 1 to 10 or more, or 4 to 8, or any number between or more than those, of substance supply tip outlet ports. The substance supply channel can have a proximal end extending into the fluid passage of the cannula, and when gas is blown through the fluid passage of the cannula, the gas flows around the substance supply channel.

[0013] Some configurations of the system further include circumferential or non - circumferential intermittent support structures that connect the outer wall and the inner wall, for example, two or more, from four to eight, or from six to ten or more, or any number in between, or more circumferential and / or non - circumferential intermittent support structures. These support structures can be used to provide a connection between the inner tube, chamber or wall of the system and the outer tube, chamber or wall.

[0014] The substance supply channel can surround at least a part of the expansion 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 an outer wall and an inner wall, and a space between the inner wall and the outer wall, and the space between the inner wall and the outer wall can include a substance supply channel, and the inner wall can include the expansion fluid passage of the handpiece, the fluid passage of the cannula body, or the fluid passage of the cannula base or tip.

[0015] The substance supply channel can be the tube within the expansion 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 supply channel tube can extend within the cannula and be capable of advancing to the distal tip of the device. The substance supply channel tube can have a distal end that reaches near the cannula outlet port.

[0016] The substance supply channel, the elongated body of the substance supply channel, the substance supply tip and / or the substance supply outlet port can have any suitable size. The substance supply channel, the elongated body of the substance supply channel, the substance supply tip and / or the substance supply outlet port can have any suitable length.

[0017] Some configurations of the system further comprise a second material supply channel. For example, a plurality of internal supply chambers can be separated by a support structure that connects an outer wall and an inner wall. The material supply channel and the second material supply channel can each be configured to provide a separate material, such as a polyethylene glycol solution and a triethylamine solution. The material supply channel and the second material supply channel may each have a separate material. For example, one chamber can contain one bioadhesive material and the other chamber can contain an activating substance. Other materials may also be provided within one or more chambers. For example, in one configuration, the first chamber can contain a bioadhesive, the second chamber can contain a curing agent, and the third chamber can contain a drug (e.g., an anti-inflammatory agent, an antibiotic, etc.), and the struts or support structures can be considered to 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 material supply channel within the distal tip.

[0018] Any configuration of the system can have a material dispenser. The material dispenser can have a base having a well or a series of wells. The base can be made of plastic, metal, or glass. Each of the well or series of wells can hold a material such as a bioadhesive material.

[0019] Any suitable material may be used. The bioadhesive material can optionally include a ReSure™ sealant, a polyethylene glycol hydrogel, a polymer gel, a bilayer hydrogel, a cyanoacrylate, a fibrin glue, a polyethylene glycol solution, or a triethylamine solution. The bioadhesive material can include a resin. In any configuration, a substantially spherical film of a material encapsulating a material bubble or an inflatable fluid can have any suitable diameter or size. The diameter can vary, expand, and / or decrease within, between, or among the aforementioned ranges.

[0020] Some configurations relate to a handheld device for applying bioadhesive bubbles to the retina. The device includes an elongated body having a first end and a second end, where the first end includes a handle and the second end includes a cannula having an exit port, and at least one inflation fluid passage extending from the first end toward the second end; an elongated body; and a distal tip at the second end configured to generate bioadhesive bubbles from a bioadhesive when gas or liquid flows through the inflation fluid passage, maintain the bubbles at the distal tip when the flow of gas through the inflation fluid passage is stopped, and release the bubbles when the bubbles touch the retina, or when gas flows through the inflation fluid passage again, or when the tip of the cannula is heated or cooled, or when the bubbles are disengaged from the distal tip using a second instrument.

[0021] Some configurations relate to a handheld device for applying bioadhesive bubbles to the retina. The device is configured to generate bioadhesive bubbles from a bioadhesive when gas or liquid flows through an internal fluid passage, maintain the bubbles at the distal tip when the flow of gas through the internal fluid passage is stopped, and release the bubbles when the bubbles touch the retina, or when gas flows through the internal fluid passage again, or when the tip of the cannula is heated or cooled, or when a second instrument is used to disengage the bubbles from the distal tip.

[0022] Some configurations relate to a kit including the systems or devices described herein. Some configurations of the kit further include a second system or device, where the systems or devices are each disposable after single or limited use. Some configurations of the kit further include an adhesive biomaterial, a substance dispenser, and / or a tip plug or protective cover.

[0023] 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 the repair of the eye or retina. Some configurations relate to a method of repairing a retinal tear, the method comprising generating a bioadhesive bubble comprising a substantially spherical film of a bioadhesive material encapsulating an inflation fluid using a system, device, or kit, and applying the bioadhesive bubble from the system, device, or kit to the eye or retina.

[0024] Some configurations relate to a system for applying a bioadhesive bubble to the retina or other biological tissue. The system can have a handpiece and / or a cannula. The handpiece can have an elongated body including 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 comprises 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 a fluid passage in fluid communication with the outlet port, configured to receive the inflation fluid that has passed through the inflation fluid passage and exit the outlet port, and the distal tip can have a flat, non-inclined surface including a cannula outlet port at the distal end of the distal tip, the surface being configured to support a bioadhesive bubble generated when the inflation fluid flows through the inflation fluid passage to the cannula outlet port at the distal end of the distal tip and through the bioadhesive material contained within the handpiece or cannula, thereby generating a substantially spherical film of a bioadhesive material encapsulating the inflation fluid. There can be no inclination within the distal tip or the cannula outlet port.

[0025] In a first aspect, a device for applying bubbles of a substance to a tissue surface, the device comprising: a cannula having a proximal end portion, a distal end portion, and an intermediate portion extending therebetween; a distal tip at the distal end of the distal end portion of the cannula, the distal tip having a bubble support surface and an outlet port extending through the bubble support surface; an inflation fluid passage extending through at least the intermediate and distal portions of the cannula and in fluid communication with the outlet port; a source of inflation fluid; and an actuator coupled to the source of inflation fluid and configured to selectively advance inflation fluid through the inflation fluid passage and the outlet port upon actuation of the actuator. In an operative state, the distal tip can be configured to support a layer of the substance on the bubble support surface such that the layer of the substance completely covers the distal port. Further, when the device is in an operative state, the device can be configured to form at least one bubble of the substance from the layer of the substance on the bubble support surface of the distal tip by advancing inflation fluid from a fluid source through the outlet port. Further, the device can be configured to move at least a portion of the bubble from the distal tip to the tissue surface to treat a defect on the tissue surface. This can be achieved, in any configuration disclosed herein, by moving the cannula, distal tip, applicator portion, loop, or device or component so that the bubble, substance, loop, applicator portion, or other means covers the tissue surface and / or the defect in the tissue surface such that the substance spreads to a desired amount around the tissue surface and / or the defect, which can be performed in multiple steps.

[0026] A device for applying bubbles of a substance to the 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 retention ridges, lips, and / or rims configured to support the bubble; (c) A curved recess is formed in the bubble support surface; (d) The device can be configured to support a plurality of bubbles on the bubble support surface; (e) The proximal end of the device has a handle portion, and the handle portion is configured to support at least an actuator and a source of inflation fluid; (f) The device can be configured to form bubbles that include a spherical film of a substance that at least partially encloses the inflation fluid advanced through the outlet port; (g) The device can be configured to form bubbles that include a spherical film of a substance that only partially encloses the inflation fluid advanced through the outlet port; (h) The actuator includes a compressible bladder configured to discharge the inflation fluid from a source of inflation fluid within the bladder through an inflation fluid passage and an outlet port; (i) The inflation fluid actuator includes a roller wheel movable along a compressible bladder configured to discharge the 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) The device further has a substance supply channel for supplying the substance to the distal tip; (l) The substance supply channel can be in fluid communication with a substance source; (m) The substance supply channel can be integrated within a cannula; (n) The substance supply channel has an elongated body having a proximal end and a distal end having at least one opening therein, and the elongated body is advanceable through an inflation fluid passage to the distal tip at the distal end portion of the cannula; (o) The substance supply channel can be inside the inflation fluid passage of the cannula or surrounded by at least a portion of the inflation fluid passage of the cannula; (p) The cannula has an outer wall and an inner wall, the inner wall has the substance supply channel, and the space between the inner wall and the outer wall has the inflation fluid passage of the device; (q) It further has a second substance supply channel;(r) The substance supply channel and the second substance supply channel each contain a separate bioadhesive substance and / or activator; (s) The bubble support surface may be inclined; (t) Further having a substance dispenser; (u) Further having a cauterization component configured to raise the temperature of at least the distal tip of the device.;

[0027] In another aspect, a system for treating a defect on a tissue surface, the system having a first device for generating bubbles of a substance for treating a defect on a tissue surface, the first device having a first sleeve having a proximal end portion, a distal end portion, and an intermediate portion extending therebetween, a distal tip at the distal end portion of the first sleeve, the distal tip having an outlet port extending through the distal tip, a fluid passage extending through at least the intermediate portion and the distal portion of the first sleeve and in fluid communication with the outlet port, and a supply portion of the substance.;

[0028] A system for treating a defect on a tissue surface can optionally include one or more of the following features in any combination. (a) The device is configured to support a layer of material over the distal tip outlet port when the first device is in an operable state; (b) When the first device is in an operable state, the first device can be configured to form at least one bubble of material from the layer of material on the bubble support surface at the distal tip by passing fluid through the outlet port, the bubble having a spherical film surface; (c) Further comprising a second device for applying a bioadhesive material to the retina, the second device having a second sleeve having a proximal end, a distal end, and a passage extending along the length of the sleeve from the proximal end of the sleeve to the distal end, an applicator having an elongate body and an applicator tip coupled to the distal end of the elongate body movable within the second sleeve, the applicator portion being self-expandable from a first crimped state to a second expanded state upon exiting the distal end of the second sleeve, the applicator tip having a greater width in the second expanded state, the applicator; (d) The system can be configured such that at least one bubble can be moved from the first device to the applicator tip of the second device and from the applicator tip of the second device to the tissue surface having the defect; (e) Further comprising a patch removably supported on the surface of the applicator tip, the patch being supported such that at least one bubble can be moved from the first device to the patch supported by the applicator tip of the second device and such that the patch can be moved from the applicator tip of the second device to the tissue surface having the defect.

[0029] In another aspect, a method of repairing a retinal tissue defect, the method comprising advancing a substance delivery device having a cannula and a distal tip toward the defect; providing a layer of a bioadhesive substance over an outlet port of the distal tip of the device such that the layer of the bioadhesive substance completely covers the outlet port; forming a bubble of the bioadhesive substance on a support surface of the distal tip by advancing an inflation fluid through the outlet port and the layer of the bioadhesive substance, the bubble having a generally spherical film that can at least partially adhere to the support surface of the distal tip and extends away from the support surface of the distal tip; and moving the bubble to the retinal tissue so as to at least partially cover the defect of the retinal tissue.

[0030] The method of repairing a retinal tissue defect can optionally include one or more of the following features in any combination. (a) Moving a plurality of bubbles of the bioadhesive substance to the defect and / or the retinal tissue adjacent to the defect; (b) Moving the bubble to the retinal tissue so as to at least partially cover the defect in the retinal tissue includes moving at least one bubble of the bioadhesive substance to a first surface of a patch and placing the patch over the defect such that the first surface of the patch having the bioadhesive substance thereon can contact at least the retinal tissue adjacent to the defect.

[0031] In another aspect, there is a handheld device for applying a bioadhesive bubble to the retina. The device has a proximal end with a handle, a distal end with a distal tip, and an internal air passage from the proximal end to the distal end. The handheld device for applying a bioadhesive bubble to the retina can optionally include one or more of the following features in any combination. (a) The device can be configured to generate a bioadhesive bubble from a bioadhesive when gas flows through the internal air passage; (b) The device can be configured to maintain a bubble on the distal tip when gas flow through the internal air passage is stopped; (c) The device can be configured to release the bubble to the retinal tissue at least when the bubble can be advanced to contact the retinal tissue.

[0032] In another aspect, there is a handheld device for applying a bioadhesive substance to the retina. The device has a tubular body having a first end and a second end, an outlet port at the second end, a first passage extending from the first end to the outlet port, an elongated body having a loop at its distal end, the elongated body being movable forward and storable within the first passage such that the loop extends from the outlet port and can contact the surface of the retinal tissue, and a source of bioadhesive substance configured to be applied to the loop. The device can apply the bioadhesive substance to the loop and can be configured to move the bioadhesive substance from the loop to the surface of the retinal tissue by contacting the surface of the retinal tissue with the bioadhesive substance on the loop.

[0033] In another aspect, use of a system, device, or method of any of the foregoing aspects. In the art, there is a need for user-friendly devices and methods for applying therapeutic substances to the eye or other biological tissues. Disclosed herein are, for example, but not limited to, systems, devices, and methods for applying substances to tissue surfaces for applying biological substances. Some non-limiting examples of the use of any of the devices and methods disclosed herein include applying a biological substance, such as a bioadhesive, to eye tissue (e.g., retinal tears, holes, or detachments), as well as applying a bioadhesive to the sclera, conjunctiva, and cornea, and applying a biological substance, such as a bioadhesive, to gastrointestinal tissue, colon tissue, etc. to seal perforations or tears therein. However, embodiments of the devices and methods disclosed herein are not limited to the delivery of therapeutic substances or to ophthalmic, medical, or biological uses. The devices and methods disclosed herein can be used for the delivery of any desired or suitable material in any biological, non-biological, mechanical, or other desired use.

[0034] Embodiments of devices and systems for applying a bioadhesive substance to the retina include an outer sleeve having a proximal end, a distal end, a passage extending along the length of the elongated body, and an opening at the distal end of the elongated body, an applicator tip including an elongated body having a proximal end and a distal end, an applicator portion coupled to the distal end of the elongated body, and a substance supply conduit extending along the length of the device through which the bioadhesive substance can pass such that the bioadhesive substance can be applied to at least the applicator portion of the applicator tip. Some embodiments of the device can also have a source of bioadhesive substance in fluid communication with at least the substance supply conduit.

[0035] Any embodiment of the devices, systems, and methods disclosed herein can, in additional embodiments, include any combination of one or more of the following features, components, and / or details with any other features, components, and / or details of any other embodiment disclosed herein. The applicator tip is configured to move between a first position where the applicator portion is received within the outer sleeve and a second position where the applicator tip is disposed beyond the opening at the distal end of the outer sleeve; the applicator portion can have a first width when the applicator portion is in the first position and a second width when the applicator portion is in the second position, and the second width is substantially greater than the first width; the material supply conduit is a passage extending through at least the elongate body of the applicator tip; the material supply conduit can include a separate cannula disposed within the outer sleeve and telescoping and retractable relative to the outer sleeve; the material supply conduit can be axially fixed relative to the outer sleeve and can have an opening adjacent an end of the outer sleeve, whereby a bioadhesive material can be exuded onto the applicator portion along at least a portion of the length of the applicator portion as the applicator portion advances distally; the device includes a handle coupled to the proximal end of the outer sleeve; the applicator portion can be biased to curl a first side toward a second side of the applicator portion when the applicator tip is retracted proximally within the outer sleeve; the elongate body of the applicator tip extends through the outer sleeve to at least the proximal end of the device, and the elongate body of the applicator tip can be integrally formed with the applicator portion; the applicator portion can be non-removably coupled to the elongate body of the applicator tip; the applicator portion can be configured to be removed from the patient's body using the device; the applicator portion can be configured to move to the first position before the device is removed from the patient's body; the applicator portion can be biased to fold within the passage of the outer sleeve when the applicator portion is retracted proximally within the outer sleeve;The applicator portion can be biased such that when the applicator tip is retracted proximally within the outer sleeve, the first side of the applicator portion is folded toward the second side of the applicator portion; the applicator portion can be biased such that when the applicator tip is retracted proximally within the outer sleeve, the first side of the applicator portion is crushed toward the second side of the applicator portion; and / or the passage through at least the elongate body of the applicator tip communicates with an opening at the proximal end of the applicator portion.;

[0036] Any embodiment of the devices, systems, and methods disclosed herein can, in additional embodiments, include any one or more of the following features, components, and / or details in any combination with any other features, components, and / or details of any other embodiment disclosed herein. A passage through at least an elongate body of the applicator tip communicates with a plurality of apertures passing through a first surface of the applicator portion; the applicator portion can have an asymmetric shape such that a first side of the applicator portion on one side of an axial centerline of the applicator portion has a different shape than a second side of the applicator portion on the opposite side of the applicator portion, and the first and second sides are divided by the axial centerline of the applicator portion; the applicator portion can have an asymmetric shape, the asymmetric shape can have a first length of a first side of the applicator portion on one side of the axial centerline of the applicator portion that can be longer than a second length of a second side of the applicator portion on a second side of the axial centerline of the applicator portion; the first side can have a first transition portion having a first length in the axial direction, the second side can have a second transition portion having a second length in the axial direction, and the first length of the first transition portion can be shorter than the second length of the second transition portion; the applicator portion can have an asymmetric width, and the applicator portion can have an asymmetric thickness in the width direction such that a thickness profile of an applicator portion on a first side of the applicator portion can be different from a thickness profile of an applicator portion on a second side of the applicator portion; the first side can be more flexible than a second side of the applicator portion; and / or the applicator portion can be configured such that when the applicator portion is drawn into an outer sleeve, the first side contracts before the second side contracts; the applicator portion can have an asymmetric width and an asymmetric thickness.

[0037] Any embodiment of the devices, systems, and methods disclosed herein can, in additional embodiments, include one or more of the following features, components, and / or details in any combination with any other features, components, and / or details of any other embodiment disclosed herein. The outer sleeve can have a notch at its distal end. The outer sleeve can have a notch at its distal end configured to facilitate contraction or size reduction of the applicator portion when the applicator portion is stored at the distal end of the outer sleeve. The notch can be generally "V" shaped, or can have a tapered shape that narrows in the proximal direction, and / or the notch can be generally "U" shaped, or can have a uniform width and a rounded end at the proximal end of the notch.

[0038] Embodiments of devices and systems are disclosed herein for applying a substance to a tissue surface that include a cannula having a proximal end, a distal end, and a passage extending along the length of the cannula and through the applicator tip. In some embodiments, the applicator tip can include an elongate body having a proximal end and a distal end, an applicator portion coupled to the distal end of the elongate body, a passage through at least the elongate body of the applicator tip, a handle coupled to the proximal end of the cannula, and a source of substance in fluid communication with at least the passage extending along the length of the elongate body of the applicator tip.

[0039] Any embodiment of the devices, systems, and methods disclosed herein can, in additional embodiments, include one or more of the following features, components, and / or details in combination with any other features, components, and / or details of any other embodiment disclosed herein. The applicator tip can be configured to move along the length of the cannula passage between a first position where the applicator portion is received within the cannula and a second position where the applicator tip extends beyond the distal end of the cannula; the applicator portion can have a first width when the applicator portion is in the first position and a second width when the applicator portion is in the second position, and the second width can be substantially greater than the first width; the applicator portion can be biased to crush within the cannula passage when the applicator tip is retracted proximally within the cannula; the substance can be a bioadhesive; the tissue can include ocular tissue; the applicator portion can be biased such that when the applicator tip is retracted proximally within the cannula, a first side of the applicator portion rolls toward a second side of the applicator portion; the applicator portion can be biased such that when the applicator tip is retracted proximally within the cannula, a first side of the applicator portion folds toward a second side of the applicator portion; the applicator portion can be biased such that when the applicator tip is retracted proximally within the cannula, a first side of the applicator portion crushes toward a second side of the applicator portion; a passage through at least the elongate body of the applicator tip communicates with an opening at the proximal end of the applicator portion; and / or a passage through at least the elongate body of the applicator tip can communicate with a plurality of openings passing through a first surface of the applicator portion.

[0040] Embodiments of a method for repairing retinal tissue defects are disclosed herein. The method can include advancing a device for applying a bioadhesive material toward the defect, covering at least a portion of the applicator tip of the device with the bioadhesive material, advancing the applicator tip beyond the distal end of the outer sleeve of the device, and moving the bioadhesive material from the applicator tip of the device to the defect. In some embodiments, the method can also include rounding or compressing the applicator tip to a smaller size by retracting the applicator tip into the outer sleeve.

Brief Description of the Drawings

[0041]

Figure 1

Figure 2

Figure 3

Figure 4A

Figure 4B

Figure 4C

Figure 4D

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

Figure 11

Figure 12

Figure 13

Figure 14

Figure 15

Figure 16A

Figure 16B

Figure 17

Figure 18

Figure 19

Figure 20

Figure 21

Figure 22

Figure 23

Figure 24

Figure 25A

Figure 25B

Figure 26

Figure 27

Figure 28

Figure 29

Figure 30

Figure 31

Figure 32

Figure 33

Figure 34

Figure 35

Figure 36

Figure 37

Figure 38

Figure 39

Figure 40

Figure 41

Figure 42

Figure 43

Figure 44

Figure 45

Figure 46

Figure 47

Figure 48

Figure 49

Figure 50

Figure 51

Figure 52

Figure 53

Figure 54A

Figure 54B

Figure 55A

Figure 55B

Figure 55C

Figure 56

Figure 57

Figure 58

Figure 59

Figure 60

Figure 61

Figure 62

Figure 63

Figure 64

Figure 65A

Figure 65B

Figure 65C

Figure 66A

Figure 66B

Figure 66C

Figure 67A

Figure 67B

Figure 67C

Figure 68

Figure 69

Figure 70

Figure 71

Figure 72

Figure 73

Figure 74

Figure 75

Figure 76

Figure 77

Figure 78

Figure 79

Figure 80A

Figure 80B

DETAILED DESCRIPTION OF THE INVENTION

[0042] In the following detailed description, reference may be made to the accompanying drawings that form a part hereof. In the drawings, like symbols typically identify like components unless context dictates otherwise. 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. The aspects of the present disclosure generally described and illustrated in the figures can be arranged, substituted, combined, separated, and designed in a variety of different configurations, all of which are explicitly contemplated herein and will be readily understood.

[0043] The configurations disclosed herein include devices, systems, and methods for applying a substance to a surface including a tissue surface. In any of the configurations disclosed herein, the substance can be a therapeutic substance that can be applied to tissue. The tissue of any configuration 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 or semi-liquid therapeutic substances, bilayer hydrogels, non-solids, and the like. 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.

[0044] Any of the configurations of the systems, devices, and methods disclosed herein can be configured to generate a thin film of a substance for delivery to ocular tissue such as, but not limited to, retinal tears or detachments, or to other living tissues including intravitreal, intraperitoneal, intracranial, and epidermal bioadhesive delivery. However, the configurations of the devices, systems, and methods disclosed herein are not limited to the delivery of substances to ocular, medical, or biological applications. The devices, systems, and methods disclosed herein can be used for the delivery of any desired or appropriate substance in any desired or optimal biological, non-biological, mechanical, or other application.

[0045] Some configurations include generating bubbles from an adhesive, for example, blowing bubbles. The bubbles can include a thin film that can be applied to a surface such as the retina and can be attached or detached from the back of the eye. In any configuration, the bubbles can be applied to the surface of the retina filled with air or to the surface of the retina filled with fluid. Advantages of applying a bioadhesive in this way include improved ability of the adhesive to conform and adhere to the eye and retina, as well as a reduction or improvement in the drying, curing, or activation time of the adhesive.

[0046] The configurations of the devices and methods disclosed herein are configured to enable the generation of one or more bubbles in a controlled manner such that the release of one or more bubbles from the delivery device can be controlled so that they are not released until a desired time. Further, the devices and methods disclosed herein optionally enable the reformation or new formation of bubbles after a film has been removed and dissipated by the formation of one or more bubbles during a previous operation of the device, in preparation for a next operation. The devices disclosed herein can optionally be configured for use in any desired tissue, including eye tissue, the walls of the mouth or palate, the nose, the vagina, or other tissues, in any orientation including horizontal, vertical, inverted, or otherwise, without limitation.

[0047] As used herein, the term "bubble" can mean a complete spherical membrane or body of a substance, a film of spherical or curved shape or surface (including, but not limited to, a hemispherical shape of a substance), a single bubble or multiple bubbles (either separate or connected together like a foam). All uses of the term "bubble" in this specification are meant to include any one or all of these examples of bubbles described elsewhere in this specification or description.

[0048] For example, without limitation, any of the devices disclosed herein can be configured to form bubbles, which means that the device can form a spherical membrane or body of a substance, a spherical or curved shape or film on the surface, without limitation, a partial sphere or hemisphere shape of a substance, a complete sphere of a substance, a single bubble or a plurality of bubbles, which can be separate or connected to each other such as in a foam.

[0049] In any configuration disclosed herein, a substantially spherical film of bubbles or a bioadhesive substance can have a diameter in the range of about 0.1 mm to about 15 mm or more (up to at least 100 mm), or about 0.5 mm to about 5 mm, or about 1 mm to about 3 mm, or any value within these ranges to a value within these ranges.

[0050] Some configurations relate to systems and / or devices for generating and / or applying bioadhesive bubbles to a surface. The surface can be a biological surface such as the retina. The system or device can optionally include an elongated body having a handle portion and a distal port. The elongated body can have a proximal end, a distal end, and an intermediate region extending therebetween. At least the proximal portion of the elongated body can include the handle portion. The distal end of the elongated body can have an outlet port. In any configuration, the elongated body, which can be a cannula as described in more detail below, can include at least one inflation fluid passage, or optionally, a plurality (e.g., two, three, four or more) of inflation fluid passages extending partially or completely therethrough. The inflation fluid passage can be in fluid communication with the outlet port and can extend proximally towards the intermediate region of the elongated body.

[0051] In any configuration, the fluid passageway can be configured to enable the supply of a fluid, which can be a gas or other inflation medium, through the body of the device towards an outlet port. The fluid passageway can be in fluid communication with the outlet port. In any configuration, a fluid such as a gas or other inflation medium can be advanced through the fluid passageway to apply a positive pressure to a substance to expand the substance, or to form one or more bubbles from a curved or spherical film or substance.

[0052] The inflation medium can, for example, expand or otherwise expand a film or membrane of a substance (optionally a bioadhesive substance) before applying a bioadhesive to a target tissue or tissue region. In some configurations, a surgeon can activate a source of inflation medium (which can be a gas) and supply inflation fluid through an inflation passageway. The inflation fluid can pass through the device, through the substance, and out through an opening at the distal end of the device to generate bubbles and / or spread a film of the substance over a desired surface.

[0053] FIG. 1 shows a non-limiting example of an application device 100 that can be used to provide a substance (e.g., but not limited to, including a bioadhesive) to a target tissue. The device 100 can include a handle 102 having an inflation fluid source 104, which can optionally include an air bladder, and the air bladder can be coupled to a body member 106 having a fluid passageway 107 extending therethrough. It should be understood that any other inflation fluid source, such as an air / gas supply line instead of an air bladder, or any other type of inflation fluid source disclosed herein or used in the industry currently or in the future, can be used.

[0054] The expansion fluid source 104 can be filled with an expansion fluid 105 that can be used to generate bubbles. The expansion fluid source 104 can be in fluid communication with a fluid passage 107 such that the expansion fluid can selectively discharge or communicate from the expansion fluid source 104 through the fluid passage 107. The body member 106 can optionally be formed from a flexible, rigid, semi-rigid, or other suitable material or component.

[0055] In any configuration disclosed herein, the expansion fluid can include gases such as air, sulfur hexafluoride (SF6), perfluoropropane (C3F8), and / or nitrogen or other inert gases, or any combination thereof. The expansion fluid can include liquids such as water, heavy liquids such as perfluoro-n-octane, buffers, solvents and / or oils such as silicone oil. The expansion fluid enters and / or fills the bubbles of the bioadhesive substance and expands the bubbles when the expansion fluid enters and / or fills the bubbles. The expansion 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% of SF6. The expansion 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% of C3F8. For example, the expansion fluid can include 20% SF6, 12% C3F8, and 68% air, or the expansion fluid can include 20% SF6, 14% C3F8, and 66% air. The expansion fluid can also include liquids such as water, heavy solvents or liquids such as perfluoro-n-octane, oils, or oil-water mixtures.

[0056] Connector 110 can be connected to the end of the body member 106 to enable selective connection and disconnection of an end piece 114 that can be or include a cannula. The connector 110 can include an optionally screwable connector portion 116 configured to reversibly couple with the proximal end portion 118 of the cannula 114. In any configuration, the connector portion 116 can have an opening 120 or a passage therethrough configured to be threaded to engage in a threaded engagement with the proximal portion 118 of the cannula 114. In some configurations, the opening 120 can have an internal thread configured to engage with an external thread of the proximal portion 118 of the cannula 114. Optionally, the connector 110 can have an external thread thereon configured to engage with an internal thread inside the proximal portion 118 of the cannula 114.

[0057] The connector 110 can optionally include a luer lock connector configured to reversibly connect with the cannula 114. The cannula 114 can have a generally uniform or consistent cross-sectional size along the length of the cannula 114. In some configurations, as shown, the proximal portion of the cannula 114 can have a larger cross-sectional size or diameter compared to the middle and distal portions of the cannula 114. The cannula 114 can have therein a passage 122 that can be in fluid communication with the opening or passage 120 of the connector 110 and the passage 107 through the body member 106. The cannula 114 can have an end 130 (also referred to herein as the distal tip) having an opening 132 in fluid communication with the passage 122 extending therethrough.

[0058] Furthermore, device 100 can optionally include one or more valves 140, such as a one-way valve or other flow restrictor, at any position along the length of passageway 107. The valve 140 can prevent leakage or inadvertent discharge of the expansion fluid 105 within passageway 107 or expansion fluid source 104, and / or can be configured to prevent backflow into source 104. One or more such valves can also be disposed within cannula 114.

[0059] Note that the components shown in FIG. 1 and several other figures are not drawn to scale. For example, in other configurations, cannula 114 can be longer or shorter than that shown in FIG. 1, or can have a larger or smaller cross-sectional size compared to the example shown in FIG. 1.

[0060] In any configuration, connector 110 can be configured to engage with any of a variety of different cannulas 114. The variety of different cannulas 114 can have a variety of different cross-sectional sizes and / or shapes, a variety of different lengths, as well as a variety of other different features and characteristics. Referring to device 100 shown in FIG. 1, the distal tip 130 of cannula 114 can be smaller or larger than that shown in FIG. 1 relative to one or more of the other components, including connector 110 and body member 106.

[0061] 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 expansion fluid passageway 122 extending through the cannula body. The fluid passageway 122 can be in fluid communication with an outlet port 130 and can be configured to communicate expansion fluid 105 via expansion fluid passageway 122 and outlet port 132.

[0062] When the inflation fluid flows through the material located within or on the distal tip 130 of the cannula 114, it is possible to generate bubbles or a curved film or membrane of the material that partially or completely surrounds or encapsulates the inflation fluid. In some configurations, the curved film or membrane of the material can completely surround the inflation fluid and can have a spherical shape. The surface of the distal tip 130 of the cannula 114 (which can be angled or inclined, but not necessarily so) can remove the material (which can be in the form of bubbles) from the cannula 114 and allow it to be deposited on the target tissue (e.g., a retinal tear) accurately and with a reduced risk of further tissue trauma. Additionally, any of the devices disclosed herein that include the device 100 can be configured to maintain the bubble at the distal tip when gas flow through the inflation fluid passageway is stopped and / or to release the bubble when the bubble can contact the retina or when gas again flows through the inflation fluid passageway.

[0063] 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 and subsequently generate bubbles of the material. The end face 131, if plural as in some configurations, may be inclined with respect to the longitudinal axis of the cannula body and / or at least one cannula outlet port. At least one end face 131 can be configured to support a film of material (which can be a bioadhesive in any of the embodiments 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 the material. For example, in some configurations, when an inflation fluid selectively advances through the fluid passage 122 to at least one cannula outlet port 132 and / or through the material housed within the handpiece or cannula, a second state of the film can be formed when generating a generally spherical or curved film of the material. In configurations where the material is in the form of bubbles in the second state, the bubbles can completely enclose around the volume of the inflation fluid.

[0064] As shown in FIG. 2, the end face 131 can be substantially planar. For example, FIG. 2 shows a side view and FIG. 3 shows a top view of the distal tip 130 with a flat inclined bubble port. The illustrated distal tip can also have a material retention rim 133. The outlet port 132 can be in the same plane as the end face 131 and can be at an angle of about 30 degrees, or about 40 degrees, or from about 30 degrees or less to about 45 degrees or more with respect to the longitudinal axis extending through the cannula 114. As shown in FIGS. 2 and 3, the entire rim of the cannula outlet port 132 can be in substantially the same plane as the end face 131. The material retention rim 133 of the end face 131 can be configured to support the bubble when the bubble is formed, expands, and is located on the material retention rim 133. The material retention rim 133 can be configured to prevent the material from falling from the distal tip 130 when the device is being navigated towards the target tissue surface or the eye.

[0065] Figure 4A shows an example of the formation of a bubble 146 containing a substance 150 filled with an expansion fluid 105 on the distal tip 130 of the device. The substance 150 is shown at the rim of the distal tip 130. The bubble is formed by passing the expansion fluid 105 through the distal opening 132 of the device covered by a film or layer of the substance 150. As the expansion fluid 105 continues to advance through the distal opening 132, the film or layer can stretch into a spherical or bubbly shape, and as the bubble expands as shown in Figure 4A, more of the substance 150 is drawn into the bubble or the existing substance stretches, and the substance 150 is used to form the bubble 146. The bubble 146 is formed when the expansion fluid 105 advances through the distal port 132 through the passage 122 of the cannula 114. The expansion fluid 105 fills the internal space within the bubble 146.

[0066] When the bubble 146 is formed or expanded to the desired size or wall thickness, the surgeon or user can advance the distal tip 130 of the device having the bubble thereon to the desired treatment position as shown in Figure 4B. The distal tip 130 of the device can be used to advance the bubble 146 containing the substance in a controlled manner toward a defect 151 in the tissue or object surface 153 as shown in Figure 4B. Thereafter, the distal tip 130 can be further advanced toward the defect to extend the bubble and spread the substance over the defect 151 and the target surface 153, thereby bringing the bubble 146 into further contact with and pressing against the defect 151 (which can be a retinal defect) or the surface 153 of the object.

[0067] The bubble 146, and thus the substance 150, can then be released from the distal tip in a plurality of different ways. For example, by continuing to advance the distal tip 130 toward and / or against the target tissue surface and / or defect, or by continuing to expand the bubble, the bubble can be ruptured against the target tissue surface. The distal tip can be made from a hydrophobic or other material configured to eliminate or reduce the surface tension of the substance against the distal tip, such that at least a portion, or most or substantially all of the substance used to form the bubble can be deposited over the defect or against the target tissue surface. Further, as described below with reference to FIG. 43, the applicator device 1002 can be used to remove the bubble from the distal tip and / or apply or rupture the bubble against the defect or target surface. Further, in some configurations, the movement of the distal tip against the target surface can apply a shear force to the bubble that can rupture or dissipate the bubble and cause it to adhere to the target surface. In some configurations, a needle or other piercing element (both of which can optionally have a blunt or sharp end face) or other suitable piercing instrument can be advanced through the distal tip or separated from the distal tip toward the bubble to rupture the bubble against the target tissue surface. Further, any of the other devices or components described herein configured to facilitate the release of the bubble from the distal tip can be used to facilitate the release of the bubble from the distal tip.

[0068] Optionally, the distal tip 130 of the device can be moved proximate to the defect or target location before the bubble is fully or partially or substantially inflated, such that the bubble can simply inflate against the defect or target surface. Thereafter, as shown in FIG. 4D, the distal tip 130 can be retracted or withdrawn from the target location, leaving the substance 150 deposited against the target surface 153 to cover the defect 151.

[0069] Any configuration of the devices or methods disclosed herein can include a liquid reservoir or chamber, along with means for applying liquid from said reservoir to the distal end of a film holding member (such as a ring or loop like a flexible loop) or cannula to form a film thereon, such that each time the device is actuated and / or brought into contact with the retina to remove the film, additional liquid for providing a new film can be applied to said ring by storing the ring, preparing the device for a next use.

[0070] In any configuration, the substance can be provided from a reservoir, which may be in the form of a cartridge, absorbent material, or chamber, the reservoir may be removably attached to the device, integrated into the device, or otherwise advanced into an internal passageway of the device, such as an inflation fluid passageway. The device can optionally be configured such that when said cartridge or chamber is emptied, it can be easily exchanged with a full cartridge, absorbent material, or double-structured chamber.

[0071] Any configuration disclosed herein can be configured to have a substance supply conduit or chamber within the handle portion and / or cannula, or can be configured to be advanceable within a cannula such as, but not limited to, handle and / or 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 elongate 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 is discharged from the end of the substance supply channel to the opening at the distal tip of the cannula to provide and / or replenish the substance at the distal tip to form a bubble element. The substance supply channel can optionally be advanceable and stowable within the inflation fluid passage of the cannula. In some configurations, as shown in FIG. 7, one or more substance supply channels can be formed in the wall portion of the cannula, thereby providing a stable supply of substance to the distal tip without the need for a separate device therefor.

[0072] Referring to FIGS. 5 and 6, in some configurations, the material supply channel or tube 158 can have a separate elongated body 160 that can be advanced within the inflation fluid passage of a cannula (not shown in FIG. 5). The elongated body 160 can have a passage 162 that extends through the length of the elongated body 160 and 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 advanced without restriction through the inflation fluid passage of the cannula in which the supply channel 158 is configured to cooperate. For example, the elongated 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 can be 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 can have a shape and angle that generally conforms to the shape and angle of the end of the inner surface inside the inflation fluid passage and the inner surface inside the cannula, and a size that is slightly smaller than the inflation fluid passage.

[0073] The supply channel 158 can be advanced distally within the expansion fluid passageway inside the cannula of the bubble generating device such that the distal end 164 is adjacent to or in contact with the end of the internal passageway. Thereafter, the substance can be advanced through one or more apertures 163 to form a film spanning the distal port within the bubble generating device. In this way, the substance can be spread across the entire distal port. The supply channel 158 can thus be used to fill the tip of any cannula or device disclosed herein with the substance. The end face can have a plurality of substance delivery holes (shown in FIG. 7), or a single hole 163, as shown in FIGS. 5 and 6. Each hole can be large, for example, but not limited to, encompassing more than 50% of the end face 163 of the tip of the substance supply channel, or small, for example, but not limited to, encompassing 5 - 25% or less than 50% of the end face 164 of the angled tip of the substance supply channel. Some configurations can have five or more holes, or four to about ten or more holes, at the distal end of the supply channel.

[0074] Some configurations of the system, device, cannula, or distal tip include the space under the substance retention rim 133 and the substance supply channel 158. The space can be configured to allow the bioadhesive substance to aggregate from the substance supply channel 158.

[0075] As described above and as shown in FIG. 7, any configuration of the supply channel disclosed herein can include a substance supply tip having any desired number of openings 163 at its distal end portion, and the openings can include one opening, two openings, three openings, four openings, five openings, six openings, seven openings, or up to twenty or more openings, or five to ten openings, or any number of openings between any of the foregoing values. As described above, the substance supply channel can include a proximal end that extends within the fluid passage of the cannula. The substance supply channel can be sized such that when inflation fluid is blown through the fluid passage of the cannula, the inflation fluid can flow around the outer surface of the substance supply channel.

[0076] In some configurations, the cannula can optionally include an outer wall and an inner wall, the inner wall including the substance supply channel, and the space between the inner wall and the outer wall comprising the inflation fluid passage of the handpiece, the fluid passage of the cannula body, or the fluid passage of the cannula base or tip. The substance can optionally be advanced through the innermost conduit or inside the inner wall. The substance supply tip can include a surface that is angled relative to the longitudinal axes of the substance supply channel body and the substance supply outlet port, by any of the other angled tips or other methods of detail disclosed herein.

[0077] Another example of a cannula 170 having an internal substance supply passage 172 is shown in FIG. 8. The cannula 170 can optionally be integrally formed with the cannula and has a plurality of substance supply passages 172 extending through the cannula 170 configured to allow passage or advancement of a substance from a proximally located substance source or reservoir to the opening 176 of the distal dip 178. The arrows within the substance supply passage 172 of FIG. 8 indicate the direction of flow of the substance within the substance supply passage 172 when a surgeon or user advances the substance through the substance supply passage 172. The substance supply passage 172 can optionally communicate with a manifold 180 surrounding the opening 176 of the distal tip 178. The manifold 180 is sized and configured such that a film or membrane of the substance spanning the opening 180 of the distal tip 178 is formed as the substance advances through the passage 172, such that air bubbles 186 can be formed from the film or membrane of the substance when the inflation fluid advances through the inflation fluid passage 184 of the cannula 170. The manifold 180 can have a series of radially inwardly projecting openings, open annular portions, openings or jets configured to facilitate the formation of the film of the substance. The cannula 170 can be formed as a single piece or from a plurality of parts coupled to each other. The opening 176 can be sized and configured to ensure consistent formation of air bubbles when the inflation fluid passes through the substance, and / or consistent formation of a film of the substance supplied through the passage 172.

[0078] As described, any configuration of the devices disclosed herein can be configured such that the material supply channel surrounds at least a portion of the inflation fluid passageway of the handpiece, the fluid passageway of the cannula body, and / or the fluid passageway of the cannula base or tip. As shown in FIG. 9, for example, device 200 can have an elongated body portion 202 having an inflation fluid passageway 204 extending therethrough. The inflation fluid passageway 204 can be partially or completely surrounded by a material supply channel or conduit 206 that can be used to advance material to the distal tip 210 of device 200. The conduit 206 can be a single annular conduit or can comprise one or more openings that communicate at the proximal and distal ends or portions of the conduit 206. In some configurations, deflector 212 can be disposed at the distal end of conduit 206 and configured to direct the flow of material radially inwardly toward opening 216 at the distal end of device 200. The deflector can optionally have an annular shape. The deflector can be angled inwardly at an angle of less than about 90 degrees or can have an inclined surface to provide a more efficient flow path for the material toward opening 216.

[0079] Device 200 can optionally include a continuous (360 degree) circumferential deflector member 212 or a plurality of individual deflector members. The deflector members can be configured to hold air bubbles longer at the tip of the cannula. This configuration allows fluid to flow around an inflation fluid (which can be air, sterile air, or another inert gas, or another fluid described herein in any of the configurations disclosed herein) and form a film of material at cannula exit port 216. After the film is formed, the inflation fluid can be advanced against the film to form air bubbles. FIG. 10 shows air bubbles formed from a film of material advanced through material supply channel or conduit 206. The air bubbles can be supported by a flared opening.

[0080] In other configurations, the substance delivery channel may include a tube or cannula that may be advanced through the handpiece inflation fluid passage 362, the fluid passage of the cannula body, or the fluid passage of the cannula base or tip. The substance delivery channel tube may be advanced toward the cannula exit port to contact the distal tip or to be within the distal tip. The substance delivery channel tube may have a distal end that reaches near the cannula exit port.

[0081] Any configuration of the systems and / or devices disclosed herein can further include a second substance supply channel. The substance supply channel and the second substance supply channel can each contain a separate bioadhesive material, such as a polyethylene glycol solution and a trilysine amine solution, a hydrogel, a bilayer hydrogel, or a polymer hydrogel.

[0082] 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.

[0083] The end face of the distal tip can have an angle of 1-15°, 15-30°, 30-45°, 45-60°, 60-75° relative to the square end (in either direction), or a range including two or more of the aforementioned 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 bubbles such that the bubbles can be prevented from falling off.

[0084] The distal tips of some configurations can be configured not to have an inclined surface. For example, the distal tip may include a flat or square surface having a cannula outlet port at 90° to the longitudinal axis of the cannula body, or the distal tip may be rounded without a flat surface, and / or may have an obtuse angle.

[0085] Any configuration of the distal tip and / or the end face of the distal tip can include a retaining ridge, lip, or rim for holding or supporting air bubbles thereon. Further, the size, angle, and / or shape of the distal tip (such as distal tip 130 or any other distal tip disclosed herein) and its retaining ridge, lip, or rim can be based on other factors related to the substance, including but not limited to the use and the viscosity of the substance. For example, the substance retaining 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 retaining rim 133 can be made thicker when configured for a low-viscosity substance than for a high-viscosity substance. The cross-sectional shape of the port 132 can optionally be circular, square, oval, rectangular, triangular, pentagonal, hexagonal, star-shaped, etc. The shape can be selected based on the viscosity of the bioadhesive substance and the size or other parameters of the one or more air bubbles or foams desired to be formed.

[0086] The end face 131 may be flat, curved, or in other configurations, and a recess may be formed that slopes towards the opening 132. The recess can be angled on the inside, can have a flat cross-sectional profile, or can be curved. Any configuration disclosed herein can have a plurality of openings 132 formed in the distal end portion to enable the simultaneous formation of a plurality of air bubbles of the substance or to form a foam-like structure of the substance. Any configuration can have two or more openings, or from two to about twenty or more openings, or from four to twelve openings, or any value within these ranges.

[0087] Figures 11 and 12 show another configuration of the cannula 250. The end face 252 of the distal tip 254 of the cannula 250 may optionally be circular, oval, non-circular, or otherwise. For example, the distal tip 254 may optionally be circular, square, or rectangular. Further, the distal tip 254 can have a non-planar end face 252 as shown in FIGS. 11 and 12. The end face 252 can be inclined inwardly toward the center of the cannula 258. The end face 252 can have an inclination or angle formed around the opening 256. The opening 256 can be in fluid communication with the inflation fluid passage 258 passing through the cannula 250. The end face 252 can be at an angle A (as shown in FIG. 12) of about 45 degrees with respect to the longitudinal axis C (as shown in FIG. 12), or from about 30 degrees or less to about 90 degrees or more with respect to the longitudinal axis C, or from about 40 degrees to about 70 degrees, or from about 50 degrees to about 60 degrees, or any value within these ranges.

[0088] Further, the cannula 250 can have a hub or hub portion 260 and a connector thread 262 on its outer surface (as shown) or inner surface. The cannula can optionally include a solid cannula wall, a substance supply channel or a core or cannula fluid passage 258 through which the inflation fluid can proceed, an opening at the tip of the cannula or a cannula outlet port 256, and a space 264 configured to hold a film of a substance such as a bioadhesive substance. Similar to any configuration disclosed herein, the cannula 250 can be immersed in a substance dispenser as described below to add a substance to the distal tip of the cannula and can hold a bioadhesive substance as a film in the tip space 264.

[0089] Accordingly, in any configuration, the end of the cannula (whether angled, square, or otherwise) can have a concave or inwardly curved recess formed in its end face. Alternatively, in any configuration, the end of the cannula (whether angled, square, or otherwise) can have a convex or outwardly curved recess formed in its end face. The end face can be flared or flanged at the end and / or can include a space that holds a bioadhesive substance or provides a large surface area by means of a bioadhesive substance. The advantage of a flared or flanged face is that it can hold a film of a bioadhesive substance that forms air bubbles when a gas such as air hits the film and / or enters the film.

[0090] Some configurations of the distal tip can have multiple end faces. Some configurations of the distal tip can have only one 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.

[0091] The distal tip can, for example, include one or more grooves at the distal end. The advantage of having grooves at the distal end is that one or more grooves can assist in retaining the bioadhesive material and assist in bubble formation of the bioadhesive material. The distal tip can include from 1 to 10, or 3 to 6 (e.g., 5) grooves, or any number of grooves within or above that range in a similar number. The distal tip can include an inner surface that includes grooves. For example, FIG. 13 shows a side view of another configuration of cannula 300 having a plurality of grooves 302 formed on the inner surface of distal tip 304. The distal tip 304 can, optionally, further or alternatively include an outer surface 306 having one or more grooves 310, as shown in FIG. 14, which is a side view of the distal tip having a plurality of grooves 310 on the outer surface of the distal tip. Any configuration can optionally include an end face and can have ridges, grooves, or other patterned protrusions and / or recesses on the inner or outer surface of the distal tip of the cannula to assist in retaining material within and / or on the tip of the cannula. The ridges, grooves, or other patterns can be configured to hold or hold bubbles in place.

[0092] In any configuration, the cannula, cannula base, cannula body, and / or distal tip can have a cross-sectional diameter of 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 within these ranges. In some configurations, the cannula, cannula base, cannula body, and / or distal tip can have a cross-sectional diameter of 0.1 - 0.5 mm, 0.5 - 1 mm, 1 - 2 mm, 2 - 3 mm, 3 - 4 mm, 4 - 5 mm, 5 - 6 mm, 6 - 7 mm, 7 - 8 mm, 8 - 9 mm, or 9 - 10 mm. The cannula, cannula base, cannula body, distal tip and / or cannula exit port can have a length of from 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, cannula body, distal tip and / or cannula exit port can each include an outer diameter, an inner diameter, and a width between the inner and outer diameters that is one of 0.01 - 0.05 mm, 0.05 - 0.1 mm, 0.1 - 0.5 mm, 0.5 - 1 mm, 1 - 2 mm, 2 - 3 mm, 3 - 4 mm, 4 - 5 mm, 5 - 6 mm, 6 - 7 mm, 7 - 8 mm, 8 - 9 mm, 9 - 10 mm, 10 - 20 mm, 20 - 30 mm, 30 - 40 mm or 40 - 50 mm, and any component or feature disclosed herein can have any suitable or typical size that includes any size within any of the ranges described herein but is not limited thereto.

[0093] The retaining edge, ridge, or lip can be from 0.1 - 0.5, 0.5 - 1, 1 - 2, 2 - 3, 3 - 4, 4 - 5, or 5 - 10 mm thick. The retaining edge, ridge, or lip can be from 0.1 - 0.5, 0.5 - 1, 1 - 2, 2 - 3, 3 - 4, 4 - 5, or 5 - 10 mm in length. Some configurations include a retaining edge, ridge, or lip that can be recessed a short distance from just the tip of the cannula. The distal tip may or may not have a central air tube.

[0094] In any configuration, the opening may be exactly at the tip of the distal end. Optionally, the opening may be on the side of the tip of the distal end. The opening is on the side of the distal end, but can be proximal to the tip of the distal end.

[0095] Some configurations of the system and / or device include a circumferential or non-circumferential intermittent support structure. The intermittent support structure 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 from 4 to 10, or any number of circumferential and / or non-circumferential intermittent support structures. Some configurations include a circumferential or non-circumferential intermittent support structure 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, any number between them, or more circumferential and / or non-circumferential intermittent support structures. FIG. 15 shows an example of a distal tip 350 having an intermittent attachment or support structure 352 between a central tube 354 and an outer tube 356. The support structure can be configured to allow the passage of fluid around such a structure.

[0096] The handpiece or cannula can include an outer wall and an inner wall, and a space such as the space 358 of the cannula 350 between the inner wall and the outer wall. The space between the inner wall and the outer wall can include a substance supply channel. The inner wall can connect to the inflation fluid passage 362 of the handpiece, the fluid passage 362 of the cannula body, or the fluid passage 362 of the cannula base or tip.

[0097] In any configuration, the inflation fluid can be supplied from a source separate from the device, or from a reservoir or cartridge or absorbent material within the device, or incorporated into the device. As described, any configuration can have a fluid passageway capable of advancing a gas from a source. The device can optionally have a connector, such as a port at the proximal end, to which a tube or other conduit can be attached to enable pressurization of the contents (such as the inflation fluid) within the device, in the presence or absence of a plunger or movable plug. Any handpiece or device of any configuration 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 the user causes a flow or movement of the inflation fluid through the inflation fluid passageway, such as from the proximal end to the distal end outlet port. The handpiece can include an inflation fluid actuator connected to the inflation fluid passageway at the proximal end and configured to be engaged by a user, and the engagement can cause the inflation fluid to move through the inflation fluid passageway from the proximal end to the distal end outlet port.

[0098] The inflation fluid actuator can optionally include a roller wheel or roller ball that can be moved forward and backward to advance or retract fluid through the inflation fluid passageway, respectively. In this configuration, the roller wheel device can include a plurality of movable ribs or spokes coupled to a cylindrical outer surface configured to rotate about a central axis. In any embodiment disclosed herein, the roller wheel can be configured to discharge the inflation fluid from the bladder through the inflation fluid passageway from the proximal end to the distal end outlet port when the roller wheel is rotated or moved along the length of the tube or chamber, for example, by a person's finger, a small motor, a coil spring, or the like.

[0099] Non-limiting examples of an inflatable fluid actuator 500 that can be used with any of the device configurations disclosed herein are shown in FIGS. 16A and 16B. Actuator 500 can have a roller wheel 502 configured to move along the length of an inflatable fluid conduit 504 and compress the inflatable fluid conduit 504 to flatten and / or crush the inflatable fluid conduit 504 as the roller wheel 502 moves along the length of the inflatable fluid conduit 504. When this occurs, roller wheel 502 can press the fluid within passageway 506 distally toward the distal tip of the cannula, and the fluid can contact a film of a substance such as a bioadhesive to create bubbles. Conduit 504 can be made of an elastic tube material or a non-elastic disposable tube material that crushes as roller wheel 502 advances along the length of conduit 504. In any configuration, roller wheel 502 can roll in both the distal and proximal directions, drawing air into passageway 506 as the roller wheel moves in the proximal direction. Actuator 500 can optionally also include a second roller wheel coupled to the first roller wheel that can be joined to roll with the first roller to apply opposing forces to compress the tube between the first roller and the second roller. Some configurations can include a roller ball that can move 360 degrees forward and backward or around a point or axis in any restricted or unrestricted manner.

[0100] Some configurations include a fixed device against which the bladder moves relative to a ball, sphere, stopper, plunger, or other stop device. For example, some such configurations include a port within a handle configured to receive an adhesive substance, and the bladder containing the adhesive can be configured to move in a distal-to-proximal direction, with the ball forming a barrier against the contents of the bladder and thus discharging the bioadhesive through the distal end of the device. Some configurations include a bioadhesive packet that can be loaded into the device.

[0101] As described, the handpiece can further have a source of inflation fluid that can include an inflation fluid actuator connected to the inflation fluid passage at the proximal end. The inflation fluid actuator can be configured to be engaged directly or indirectly by the user, and such engagement can move inflation fluid from the proximal end through the inflation fluid passage to the distal end outlet port. In some configurations, the inflation fluid actuator can include other reservoirs such as a compressible bladder, a syringe, a crushable vial, or an accordion-type crushable reservoir, or other similar devices configured to expel inflation fluid from the bladder through the inflation fluid passage from the proximal end to the distal end outlet port. In some configurations, the inflation fluid actuator can have a roller wheel that is movable back and forth and can be configured to expel inflation fluid from the bladder through the inflation fluid passage from the proximal end to the distal end outlet port.

[0102] In further 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 an inflation fluid such as air. Optionally, the inflation fluid actuator can comprise 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, 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.

[0103] The expandable fluid actuator can optionally include a compressible bladder. The compressible bladder can be configured to discharge the expandable fluid from the bladder through an expandable fluid passageway to a distal end outlet port from a proximal end. The expandable fluid actuator can include a compressible bladder configured to discharge the expandable fluid from the bladder through an expandable fluid passageway to a distal end outlet port from a proximal end. The compressible bladder can have a diameter that extends from the center of the handle to 1 to 1.5, 1.5 to 2, 2 to 3, 3 to 4, or 4 to 5 times the diameter of another portion of the handle, such as an elongated body, on one or more sides of the handle or 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 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.

[0104] FIG. 17 shows a side view of an embodiment of an expandable fluid actuator 520 that can be used with any of the device configurations disclosed herein to provide an expandable fluid to the distal end or tip of a cannula and thus to a substance that forms bubbles. The configuration of the fluid actuator 520 shown in FIG. 17 can include a compressible bladder 522 having an internal air space 523 in fluid communication with an expandable fluid passageway 524 of an expandable fluid channel 526. The air bladder 522 can extend or project away from one side of the handle, such as the upper part of the handle, so that a user can apply a force F substantially in one direction to compress the air bladder 522 and advance the expandable fluid through the expandable fluid passageway 524. The actuator 520 can have a support or support surface for the compressible bladder at the bottom of the compressible bladder. The support of the compressible bladder can include a handle of the device or system, or an intermediate support structure, depending on the configuration. The air bladder can be compressible, for example, with a human finger, and air can be pushed out of the bladder.

[0105] Some configurations can include an actuator mechanism with a compression device having a normally inflated elastic air storage valve, and thus air is pushed distally through an 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 storage valve from one side. Some configurations include a trigger mechanism that compresses the air storage valve simultaneously from two or more sides. The valve may be made of a material that has sufficient elasticity to return the trigger to its normal position, but optionally, a small coiled spring may be associated with the trigger to maintain the trigger in its normal non-active position and return it to such a position after each operation.

[0106] The device can include a cannula and an associated distal tip separate from the bubble generating portion of the device, allowing air to be blown onto the retina to create a drying effect prior to the application of bubbles. In some configurations, the device can 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 device can blow air onto the target tissue.

[0107] FIG. 18 shows another configuration of an actuator 540 that can be used to advance an inflation fluid toward the distal end of a cannula of any of the configurations of the devices disclosed herein. In any configuration, the actuator 540 can have a bladder 542 having an internal space volume 543 that is in fluid communication with a passage 544 via an inflation fluid conduit or channel 546. The bladder 542 can be arranged with flexible ribs or struts, pleats, or other means to improve the flexibility and crushability of the bladder. The ribs can be configured to help the bladder 540 maintain its shape and elasticity and / or to bias the bladder back to an expanded shape. The ribs can be made of the same material as another portion of the compressible bladder, or the same material as the remaining portion of the compressible bladder, or made of another flexible material.

[0108] In any configuration, the actuator 540 can have one or more one-way valves in fluid communication with the bladder, such that air can refill the bladder when the bladder is released and expands back to its original expanded state, and prevent air from being drawn into the bladder 542 from the distal portion of the conduit 546. The bladder 542 can be sized to have any desired volume of expansion fluid contained within the bladder 542. The bladder 542 may be compressed or squeezed in any direction to discharge the expansion fluid toward the distal tip.

[0109] In some configurations, the bladder 542 may be spherical or substantially spherical and can extend in all directions radially away from the centerline of the conduit 546. In other configurations, the bladder 542 can have a hemispherical shape, or any other desired shape.

[0110] Any configuration of the systems and / or devices disclosed herein can include separate or powered means for advancing the expansion fluid through the expansion fluid passageway of the handpiece or through the expansion fluid passageway of the cannula. For example, the expansion fluid passageway can include a proximal end connected to a tube, a channel, or other passageway configured to receive the expansion fluid from an expansion fluid receptacle connected to the expansion 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 operation of a screw handle.

[0111] In any configuration, the inflation fluid actuator can include a sliding piece. The sliding piece or other inflation fluid actuator can be configured to move a plunger, such as a plunger, toward the distal end of the device. The movement of the plunger can force inflation fluid through the inflation fluid passage and / or outlet port of the handpiece and / or through the cannula inflation fluid passage and / or cannula outlet port of the cannula to generate bubbles.

[0112] Figures 19 and 20 show non-limiting examples of an inflation fluid actuator 560 with a sliding piece 562. The sliding piece 562 can include a movable part or slider 562, and the movable slider 562 can be coupled to other similar components disposed within the chamber 570 of the actuator 560 that can move with the movement of the slider 562 to change the volume of the space within the sealed diaphragm, piston, plunger, or chamber 570. The chamber 570 can optionally have a generally cylindrical shape, at least in its central portion. The slider 562 can be configured to be movable along a path or groove 564 from the proximal end 566a to the distal end 566b of the device, thereby discharging air or inflation fluid through the inflation fluid passage of the device or system. It should be understood that the slider 562 can move in both directions, thus enabling control of the amount of inflation fluid discharged from the device.

[0113] In some configurations, moving the slider 560 toward the proximal end of the device can be configured to draw air from the passage to which the chamber 570 is connected, thereby reducing the volume of the air bubble or otherwise drawing fluid from the fluid passage of the cannula. However, in some configurations, one or more one-way flow valves can be arranged to be in fluid communication with the chamber to prevent the withdrawal of air from the cannula when the slider 560 moves toward the proximal end of the device. The chamber can be refillable using a sterilized or filtered ambient or other fluid source when the slider moves proximally or from a separate source.

[0114] The device 560 can be handheld. The distal end 566b can be tapered. As the slider 560 moves from the proximal end 566a toward the distal end 566b, the fluid in the chamber 570 can be pushed through the device to apply pressure to a film of a liquid, gel, or some other non-solid composition that can be suspended across the opening of the distal end 566b. This can form air bubbles of the substance from the pores of the tapered distal end 566b. The film of the substance can be formed across a ring that can be disposed inside the distal end of the device. In other configurations, by moving the slider 562 toward the distal end 566b of the device, fluid (e.g., gas) can be pushed from the chamber 570 into the cannula of any other configuration disclosed herein, toward the distal tip of the cannula.

[0115] Some configurations can optionally include a mechanism for locking the trigger mechanism when bubbles are generated, allowing the device to be operated in the eye without the need to maintain pressure on the trigger to avoid bubble shrinkage. Further, in some configurations, a diaphragm, plunger, or piston within chamber 570 or any other chamber, e.g., a cylindrical chamber formed as part of or attachable to the handle portion, is moved by a rotational or torsional movement such as rotating a dial or other threaded component to move the diaphragm, plunger, or piston within the chamber, thereby being able to extrude the inflation fluid from the chamber into the cannula. Devices of this configuration can resist inadvertent movement due to the backpressure provided by bubbles due to the threaded nature of the actuator and can also provide greater resolution and control by the user with respect to the amount of air discharged from the chamber.

[0116] In some configurations, either or both of the proximal or distal ends can optionally include an opening capable of generating bubbles. Optionally, either rather than both of the proximal or distal ends can include an opening for generating bubbles. Both the proximal and / or distal ends can include a plurality of openings capable of generating a plurality of bubbles simultaneously.

[0117] Any configuration of the devices disclosed herein can include a one-way flow valve configured to allow a fluid such as an inflation fluid or substance to flow distally when the pressure proximal to the valve is greater than the pressure distal to the valve and to prevent backflow of the fluid or substance (i.e., proximal flow).

[0118] Some configurations include a mechanism for locking the actuator mechanism when bubbles are generated or a mechanism for preventing backflow of fluid toward the proximal end of the device when bubbles are generated. In this state, the device can be operated by a surgeon (e.g., optionally, within the eye) without the need to maintain pressure on the trigger to avoid bubble shrinkage.

[0119] The distal tip of any configuration disclosed herein can include one or more flaps that are adjacent to or cover 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 distal tip of the device or the peripheral edge adjacent to the distal tip and / or can extend across the cannula exit port.

[0120] Figures 21 and 22 show another configuration of a device 590 having an opening 592 that extends through the distal surface 593 of the distal end of the device, and the opening 592 is in fluid communication with a passage 594 that extends through the device. One or more bendable elastic flaps 596 (four are shown) selectively cover the opening 592. The flaps 596 can be made of silicon and can form a diaphragm over the opening. The flaps 596 can function or act as a valve. As shown in Figure 22, the flaps 596 can include slits 595, rounded or tapered edges, and / or holes. One or more of the flaps can each optionally include a tapered edge.

[0121] Silicone diaphragms having one or more slits and / or central holes can be used with any of the various cannula or applicator tips described herein. The silicone diaphragm can function as a valve for retaining substances inside and / or controlling bubble formation. Any slit or hole in the center of the silicone diaphragm can be of any shape. The flaps include rubber, silicone, plastic, or elastic materials.

[0122] Any configuration of the handle disclosed herein can have a junction portion. The junction portion can include a coupling end. The coupling end can be configured to reversibly or irreversibly couple with the proximal portion of any cannula configuration or elongated body configuration disclosed herein. The proximal portion of the cannula can be configured to reversibly couple with the coupling end of the elongated body or the junction portion of the handle. When the handle has an elongated body, the elongated body can include a junction portion, and the junction portion comprises a coupling end configured to interact with the proximal portion of the cannula.

[0123] The handle, cannula, or any component thereof, or other components of the device can be made of 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.

[0124] The elongated body of the handpiece, cannula, outlet port and / or inflation fluid passage can have a cross-sectional diameter, size, or width of about 20 mm to about 50 mm, or a cross-sectional diameter, size, or width of about 25 mm to about 40 mm, or a cross-sectional diameter, size, or width of 0.1 - 0.5 mm, 0.5 - 1 mm, 1 - 2 mm, 2 - 3 mm, 3 - 4 mm, 4 - 5 mm, 5 - 6 mm, 6 - 7 mm, 7 - 8 mm, 8 - 9 mm, 9 - 10 mm, 10 - 20 mm, 20 - 30 mm, 30 - 40 mm, or 40 - 50 mm. The handpiece or handle can have a length of about 4 cm to about 12 cm or more, or about 6 cm to about 9 cm, or any value within these ranges. The cannula can have a length of about 0.5 cm or less to about 10 cm or more, or about 2.5 cm to about 5 cm.

[0125] Furthermore, in any configuration, the injection and / or aspiration of the bioadhesive substance and / or the activation solution can be manually or foot-pedal controlled. Accordingly, any configuration disclosed herein can include a foot pedal. The foot pedal can be configured to discharge air or inflation fluid through a tube or channel into the inflation fluid passageway such that it flows towards the distal portion of the device and can form air bubbles at the distal tip of the device.

[0126] A liquid retention member in the form of a circular wiring can be used with any of the cannula arrangements disclosed herein. The ring can optionally be fixed to the tip of the distal end of the device by an angled arm. The liquid retention member (also referred to herein as a ring) need not be a circular ring and can take any desired shape. The liquid retention member can be adapted to hold a liquid that forms air bubbles. When the liquid is applied to the ring, a film of the liquid can be formed across the ring and held in such position until it is displaced therefrom by air or other pressure.

[0127] In some configurations, the angled arm can be integral with the ring. The arm can extend along a portion of the length of the body of the device. The angled arm of the ring can be attached to the device using any suitable component or means. The ring can have an attachment in the form of a button or any other suitable shape that extends outside the central core of the device such that it can be easily manipulated with one or more fingers. The attachment can be used to move the angled arm and the attached ring distally and proximally.

[0128] Some configurations include one or more rings that provide means for holding a film of material across the space within the ring and are capable of forming one or more bubbles when an air or gas flow is directed at the film to form bubbles. In some configurations, the ring can be fixed and immersed in a liquid to form a film across the entire ring. Some configurations include a fixed ring that can actively distribute liquid across the central opening of the ring. The ring can hold a fluid, can allow the fluid to be injected through a hollow ring, and can then exit the ring through an opening in the inner surface of the ring to produce a film of liquid across the ring opening, and can have one or more openings in the inner surface of the ring that allow bubbles to form when gas passes through the ring, which can be a hollow reservoir.

[0129] An air tube can be axially mounted within the device to direct an air flow against a film that can be held across the ring. The spacing between the ring and the end of the air reduction tube controls the action of one or more bubbles formed. Also, the volume, as well as the velocity of the air passing through the tube, can be controlled by the holes at the exit end of the tube and can affect the resulting outcome. If the end of the tube is too close to the ring, the force of the air flow may simply displace the liquid film without forming one or more bubbles, which can cause the film to break. On the other hand, if the spacing between the ring and the end of the tube is too large, the air flow dissipates before reaching the film and no bubbles are formed. By optimizing the spacing between the air tube and the ring, bubbles or a series of bubbles, whose size can be controlled by the size of the holding ring, can be formed upon depression of the valve, or a single large bubble can be formed upon each operation of the valve. Thus, by adjusting the distance between the ring and the tube, as well as by controlling the size of the holes in the tube, a desired effect can be obtained.

[0130] Some configurations of the system and / or device can include a loop. The loop can be retractable, for example, the loop extends from an end of the device such as the distal end and can be partially or fully retracted proximally within the distal tip of the device to change the size and / or shape of the loop. The loop can be stored in a handle, cannula, or distal tip according to some configurations. 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 such that a substance fills or forms a film on the wire loop. An adhesive can fill or form a film on the wire loop when the wire loop is stored and / or expanded according to the arrangement. The film can exit from the distal tip and expand or discharge into the loop.

[0131] The system or device can be configured such that after a bioadhesive substance forms a film on the flexible loop, the wire loop can be applied to a retinal hole or tear. Some configurations include methods of applying a flexible loop having a film of bioadhesive substance to a retinal hole or tear. When a wire including the film is placed on a surface such as the retina or a retinal tear, the device and substance can be configured such that the film adheres to the surface (to an extent greater than the adhesion of the film to the loop) and can be displaced from the loop.

[0132] The loop can be non-flexible and / or non-implantable. The wire or loop can include a thickness of from about 0.02 mm to about 1 mm, or 0.01 - 0.02 mm, 0.02 - 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, or 4 - 5 mm, or a range including any combination of the foregoing thicknesses. For example, the loop can optionally include a flexible suture material such as polypropylene or collagen suture and can have one of the foregoing diameters. Suitable sutures include, but are not limited to, sutures having USP designations 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 foregoing diameters.

[0133] Figure 23 shows an example of a system and / or device that can have a plunger 602, a handle 604, a cavity 606 for holding a bioadhesive substance, an extender knob 608, a rod 612, a lock connector 616, and a flexible loop 620 configured to accommodate a film of the bioadhesive substance. The loop 620 shown in Figure 23 can optionally be configured to extend further than shown.

[0134] The plunger 602 may be used to discharge a bioadhesive substance through the hollow cannula and / or within the flexible loop 620 when advanced distally by a user (e.g., using pressure from the user's finger or pneumatic pressure supplied by an external device connected to the handle). For example, the extender knob 608 may be used to extend the rod, and thus the flexible loop 620, from a retracted position as shown in FIG. 23 to a more extended position or even a more retracted position. The knob 608 and the rod 612 may be toothed such that rotation of the knob in a first direction engages the teeth of the knob with the teeth of the rod to advance the rod distally. When the knob rotates in a second direction, the teeth of the knob engage the teeth of the rod to retract the rod proximally. For example, the knob 608 may take the form of a roller wheel having teeth on its surface or a smooth surface that can move the rod distally or proximally when rotated. The teeth may optionally be formed in a direction parallel to the axis of rotation of the knob / roller wheel (not shown).

[0135] Alternatively, the knob and rod may be smooth, but contact such that rotation of the knob in a first direction advances the rod and loop distally and rotation of the knob in a second direction retracts or pulls in the rod proximally. Any configuration of the loop disclosed herein can be used to support a film of a substance such as 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 the formation of one or more bubbles using the loop. The loop may be positioned in contact with the target tissue or moved relative to the target tissue, for example, to deposit a substance carried by the loop onto the target tissue.

[0136] Furthermore, in any configuration, the loop can be temperature controlled (i.e., cooled or heated) to change the adhesion or agglomeration properties of the film adhesion of the substance to the loop, enable detachment from the film, and / or enable stronger adhesion to the film. For example, but not limited to, the wire can be heated or cooled to any desired temperature using a heating or cooling element in communication with the loop to facilitate the release of the substance from the loop.

[0137] In some configurations, bubbles can be formed from the substance held by the loop. Furthermore, in such configurations, the release of the bubbles can be achieved by squeezing or closing the loop (by pulling out the loop, advancing a clasp, clamp, or other fastener to squeeze the loop, or by other means) to release the bubbles and removing the bubbles from the device. The bubbles can be generated in a controlled manner, for example slowly, or of a controlled size. The bubbles can be generated one at a time. Once formed, the bubbles can be removed from the device to a surface such as the retina 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.

[0138] FIG. 24 shows an example of a device 640 that can have a handle or housing 641, an extender knob 648, a rod 650, a flexible loop 652 configured to support a film of a bioadhesive substance 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, the substance can be applied to the loop 652 via an injection port, through the distal end of the device, through a passageway within the housing, and / or using any of the other devices, components, or methods for advancing the substance through a cannula disclosed herein or known in the art. If the loop is disposed outside of the cannula, the substance can also be added to the loop.

[0139] FIG. 25A shows another example of the configuration of a device 670 that can include a flexible loop 678 configured to support a film of a bioadhesive material 680 across a handle or housing 672, a rod 674, a cannula 676, and a loop 678. The cannula may be removable or non-removable. Further, the loop 678 may be removable from the rod 674 such that the loop can remain in place after the material has been applied to the target tissue surface. Alternatively, the loop 678 can be retracted into the cannula 676 to release the material 680, which can be in the form of a bubble or a planar film, from the loop 678. The rod 674 can optionally extend from or proximal to the handle portion such that the user can grip and manipulate the proximal end 674a of the rod 674 to advance and retract the rod 674 distally and proximally, respectively, and rotate the rod 674 or otherwise manipulate the rod and the loop 678. Note that in some configurations, the rod can be keyed or indexed to the cannula to prevent relative rotation of the rod with respect to the cannula. The loop material in any of the embodiments described herein can include nitinol, stainless steel, nylon, or any other desired polymer or other acceptable material.

[0140] Furthermore, in some configurations, a desired substance can be applied to loop 678 and the loop can be stored within cannula 676 before the device is delivered to the surgeon or the operating room. FIG. 25B shows device 670 with rod 674, and thus flexible loop 678, withdrawn proximally relative to handle 672 such that flexible loop 678 is at least partially (or completely as shown) disposed within cannula 676. For example, but not limited to, as shown in FIG. 25B, a substance 680, which can be any within a desired range, can be pre-loaded onto the loop and the loop 678 can be stored within the cannula. A plug or seal can be placed over or within the cannula to prevent the substance from being inadvertently discharged or leaking from the device. In this pre-loaded state, device 670 is ready for use without the need for the surgeon or user to load a desired substance onto loop 678. When the device is advanced to the desired location, the seal can be removed and rod 674 and loop 678 can be advanced beyond the distal end of the cannula and the substance can be deposited from the loop onto the target tissue or surface.

[0141] Any rod of any configuration 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 conduit (hereinafter referred to as a supply conduit) through which an additional or a first substance can be advanced in a loop. For example, but not limited to, in some configurations, loop 678 (or any loop disclosed herein) can be drawn into the cannula, and while the loop is disposed within the cannula, the supply of the substance can be advanced over loop 678 beyond the distal end 674b of rod 674 (or any rod disclosed herein) through the supply conduit. Thereby, the loop can be loaded and / or reloaded with the substance within the cannula, and the loop and the substance advanced through the supply conduit are confined within the cannula to prevent inadvertent contact of the substance with unintended surfaces. Some configurations of the system and / or device can include a reinforced membrane tip. For example, but not limited to, FIG. 26 shows an example of the arrangement of the cannula tip portion 690 for administering a substance, and the device has, among other features, a cannula or body portion 691 and a reinforced membrane tip 692. Device 690 can also have a first sharp distal tip 692 that can be machined in an inclined or other manner. Tip 692 can be configured to facilitate penetration of the reinforced membrane. Device 690 can also have a distal port 696 that can be used for communicating the substance to the desired tissue surface. Port 696 can optionally include a rounded or smooth edge or bevel 698 around the distal port 696. Port 696 can include a silicone diaphragm having any of the components and / or features of the diaphragms disclosed above, or a diaphragm made of another material. The end face or tip portion 692 can be solid, inclined on both sides or only one side, have a conical shape, or be in other configurations. In some configurations, the distal tip 692 can be sharp and can be used to cut eye tissue.The cannula tip 690 and its features can be used with any configuration of the devices disclosed herein.

[0142] 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. The tip plugs 700, 720 shown in FIGS. 27 and 28 can each include a neck portion 702, 722. The neck portions 702, 722 can be shaped to conform to the dimensions of the tip of the cannula. For example, the neck portions 702, 722 can be shaped to conform to the dimensions of any substance 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 an inclined portion configured to be coplanar with the inclined portion of the distal tip. The tip plug can include an inclined portion configured to be coplanar with the inclined portion of the distal tip when the elongated member of the tip plug is disposed within the distal tip.

[0143] The distal plugs 700, 720 can each include an elongated portion 703, 723. 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 configuration of the cannula or device disclosed herein. For example, the elongated portions 703, 723 can fit inside the central tube of a system or device. The distal plug can include an elongated member having a proximal end and a distal end, and the proximal end of the elongated member can be configured to fit snugly within the distal tip (e.g., to prevent leakage of the inflation medium). The elongated portions 703, 723 can optionally be 1 - 5, 5 - 10, 10 - 20, 20 - 30, 30 - 40, or 40 - 50 mm in length. For example, as shown in FIG. 28, the elongated portions can be formed in various length ranges. The elongated members 1305, 1405 can include an elongated plug tip that fits inside the central tube of a device or system or at the distal tip of a system or device.

[0144] The distal plugs 700, 720 can include a distal plug handle or pull tab 704, 724. The distal plug handles 704, 724 can be connected to the distal ends or necks 702, 722 of the elongated members 703, 723. For example, the distal plugs 700, 720 can include fingertip tabs 704, 724 that are wider and more easily graspable compared to the elongated members 703, 723. The fingertip tabs 704, 724 can include a textured surface such as ridges, dots, and / or hash marks, or some other non - smooth surface on one or more faces. The distal plug can include a tab connected to the distal end of the elongated member of the distal plug.

[0145] 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 can be 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 strut 726. Some configurations include a continuous annular strut. Some configurations include discontinuous struts.

[0146] 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 configured to be used 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 assist 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 material via the hub of the cannula or via the tip of the cannula before securing any of the tip covers disclosed herein.

[0147] 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 becoming contaminated or cutting another article such as a fingertip or other object, and / or prevent leakage of substances contained within the cannula or device. For example, the tip plug or tip cover can be attached to the system or device during transport of the device or system. The system or device can be pre-loaded with substances such as a bioadhesive material. The pre-loaded system or device can include a tip plug or tip cover. The tip plug or tip cover holds the bioadhesive material within the pre-loaded system or device.

[0148] Any device or configuration disclosed herein can include one or more features configured to disengage a substance 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 edge, a thin metal or polymer blade, a scraper, a spatula, or other similar devices configured to slide the substance off the device. Further, in some configurations, air bubbles can optionally be scraped or plucked from the device.

[0149] 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 configuration of a cannula 750 having a fiber or wire for light or ablation. The cannula 750 can include an optical fiber 752 within the tube along the length of the cannula. The optical fiber 752 can include an angled 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 angled at an angle that matches the angle of inclination of the distal tip.

[0150] The cannula 750 can include the light 756 emitted by the end 758 of the cannula 758 or the optical fiber 752. Any configuration of the devices disclosed herein can be configured to include either one or more optical fibers 752 or other features of the cannula 750, and the cannula 750 can be configured to include any of the features of any other cannula, device, or other component or system disclosed herein.

[0151] Furthermore, additional tubes can be included that can be configured for the passage of additional materials (such as liquids) that can be expressed as a spray or droplets from the distal tip. For example, the additional material may be used to activate a bioadhesive substance. The device or system, or its components such as the handle, cannula, distal tip, light, or optical fiber, can be configured to emit light at a wavelength that activates, thickens, or cures the bioadhesive substance.

[0152] The system and / or device and / or its components can be operated to increase the temperature of the distal tip (e.g., using an internal ablation component). This can be advantageous according to some configurations that assist in disengaging the bioadhesive bubbles from the distal tip when the bioadhesive substance can be a temperature-responsive material that is more fluid and / or less cohesive at higher temperatures.

[0153] Some configurations include cryotherapy components such as a cryotherapy handpiece. The system or device can be operated to decrease the temperature of the distal tip (e.g., using a cryotherapy component). This can be advantageous according to some configurations that assist in disengaging bubbles or other forms of material from the distal tip when the bioadhesive substance can be a temperature-responsive material that is more fluid, fragile, or releasable at lower temperatures.

[0154] Some configurations of the systems and / or devices disclosed herein can have special ends that can have an increased application area, for example, to apply heat or cold air to the tissue surface or the bioadhesive. Some configurations can have a distal end portion having a solid circular shape, such as a button shape. FIG. 31 is a first perspective view of an example of an end component 770 having a button tip configuration, and FIG. 32 is a second perspective view. The button tip component 770 can have, as shown, an enlarged end face or portion 772 and an elongated arm portion 774 coupled to the end 772, which can be straight or bent. The end 772 can be solid or can have one or more passageways therethrough for an inflatable fluid, substance, or other.

[0155] The button base can include a solid floor having an opening for the distal tip that ends in the same plane as the button floor. The surface of the button can 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 substantially planar, curved, or otherwise.

[0156] The button tip cannula can be configured to be heated or cooled. The button tip cannula can be used to liquefy a viscous, solidified, or partially solidified bioadhesive by holding the heated or cooled button tip cannula on the bioadhesive until it can be converted to a liquid state that allows suction with the same or a different device. The button tip design can provide either heat or cold air to a wide area of the bioadhesive, allowing the bioadhesive to be liquefied and removed more quickly than when using a cooling or heating tip with a small surface area.

[0157] 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, viscous or semi-viscous therapeutic 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.

[0158] Examples of substances that can be used with any of the devices, systems, and methods disclosed herein and that are considered to be included in each use of the term "substance" herein include, but are not limited to, adhesives, bioadhesives, gels, hydrogels, viscous or semi-viscous therapeutic substances, bilayer hydrogels, non-solids, polyethylene glycol solutions, trilidineamine solutions, polymer hydrogels, thermoresponsive gels, polyvinyl acetate, glue, aliphatics, cyanoacrylates, epoxies, polyurethane glue, and contact cement, glycoproteins, elastic materials, proteins, carbohydrates, mucopolysaccharides, hydrogels, bilayer hydrogels, polymer hydrogels, polyethylene glycol hydrogels and other hydrogels, biomimetic substances, ReSure™ sealants, polyethylene glycol hydrogels, fibrin glue, polyethylene glycol solutions, trilidineamine solutions, glycoproteins, trilidineamine solutions, elastin proteins, carbohydrates, mucopolysaccharides, temperature-activated bioadhesives, UV or photo-activated bioadhesives, and vaccines, among others.

[0159] Any configuration disclosed herein can also be configured to use one or more substances that polymerize when the temperature of the substance reaches a threshold or range of values, such as, but not limited to, normal body temperature, or any value from about 80°F to about 100°F or higher, or from about 90°F to about 100°F or higher, or from about 95°F to about 100°F or higher, or any value within these ranges. Further, any configuration can be used to apply a cryosetting substance to the tissue surface, i.e., a substance that polymerizes when the temperature of the substance reaches a threshold or range of values, such as, but not limited to, 10°F lower than body temperature, or any value from about 70°F or lower to about 90°F, or from about 80°F to about 90°F, or any value within these ranges.

[0160] Any configuration disclosed herein can also be configured to use one or more substances that polymerize with activation by light of any number of various wavelengths or are activated by light. The activating light can be provided by a special applicator within or separate from the substance delivery device. Suitable substances that can be used typically include substances used on or approved for use on the ocular surface, including the subretinal space, vitreous cavity, or conjunctiva (above or below), and substances that can be used to close gaps within tissue.

[0161] The substance can be configured to be safe and non-toxic to the eye, injectable, and capable of binding to retinal tissue when hydrated and / or cured. The substance can also include substances having properties suitable for bubble / foam formation, including, but not limited to, adhesive and non-adhesive substances for use both inside and outside the eye or any other human or animal tissue.

[0162] After the generation of the bioadhesive bubbles and dissociation of the bioadhesive bubbles from the distal tip, the bioadhesive substance can be activated by application of a solution that can be delivered by a bioadhesive delivery device that can be constructed to have a separate tube for delivery of the bioadhesive substance and the activating solution.

[0163] The devices disclosed herein can be used for vaccine delivery, and the substances delivered by the devices can include vaccines. Vaccine delivery can include nasal delivery using bubbles, which can be a more efficient delivery than spray delivery. The devices can deliver vaccines at a higher concentration 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 applied.

[0164] It can be delivered in any of the configurations disclosed herein, and other substances contemplated as part of the term substances used herein include substances that polymerize as they approach body temperature, substances that polymerize upon activation by light of any number of various wavelengths, substances that are activated by light, and substances intended for use on the ocular surface including the subretinal space, the vitreous cavity, or the conjunctiva superior or inferior.

[0165] Any combination of the devices and / or components described herein can be provided together in a kit. Some configurations of the kit further comprise a second system or device, and the systems or devices can each be 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 comprise a tip plug or protective cover. The systems, devices, or kits described can be sterilized or pre-sterilized. The kit can include a pre-sterilized substance dispenser as described herein. The devices can be used for non-medical substance delivery including, but not limited to, adhesives, lubricants, insulators, sealants (e.g., gas joints, or pipe / tube joints). This can be preferable to Teflon (registered trademark) tape in hard-to-reach areas.

[0166] The configuration of the system and / or device can include a substance dispenser. The substance dispenser can include a base having wells or a series of wells or an open 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 can be configured for single use or disposable, or may be reusable. For example, the cannula can optionally be configured to be reusable within a period such as 1 to 60 minutes, 1 to 24 hours, and / or 1 to 3 days.

[0167] Examples of the substance dispenser 790 are shown in FIGS. 33 and 34. This example can include a base 792 having a series of wells or reservoirs 793, each containing a bioadhesive substance or pre-loaded with a bioadhesive substance, or including different cannulas or tip portions. Each well can optionally contain a single-dose or multi-dose substance. The diameter of each well can be such that the cannula fits snugly 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 a plurality of cannulas that can be removed from the base 792 and attached to the device being used.

[0168] Some configurations of the system and / or device include a method of using a substance dispenser. The method can include placing a cannula in a well containing a fixed dose of a 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. The wells of the substance dispenser can each include a removable cap or cover. The substance dispenser can be sterilized or pre-sterilized and / or can contain a sterilized liquid or substance such as a sterilized bioadhesive substance.

[0169] FIG. 35 is a cross-sectional view of a distal tip 800 having first and second substance supply channels passing through at least a portion of the distal tip. An attachment or junction 801 can be formed between the inner tube or channel 802 and the outer tube or channel 804. The attachment can be along the entire length of the channel or can have intermittent attachments.

[0170] 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 substance retaining rim 810 that extends radially inwardly adjacent to the distal end port or opening 812 of the distal tip 800. The space provided inside the retaining rim 810 can be filled with a substance and can help with bubble formation. The example of FIG. 36 shows an 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.

[0171] Another configuration of the device is shown in FIG. 37. The first reservoir 812 (or first substance supply channel) and the second reservoir 814 (or second substance supply channel) can be formed along the length of the distal tip 800. The first and second reservoirs can be divided and separated along their lengths. In the example shown in FIG. 37, the first reservoir can be configured to hold a first substance, the second reservoir can remain empty, and act as (or receive) a container for the second substance or activation solution as the second substance or activation solution advances from the end of the first reservoir. A distal tip plug can be used to prevent the outflow of substances from the distal tip. The first and second reservoirs can each be configured to hold separate biocompatible substances or activating substances, and / or the reservoirs can be configured to allow both biocompatible substances to be discharged together, enabling the biocompatible substances to mix and optionally react with each other before forming a film and bubbles.

[0172] Using any of the devices disclosed herein, biocompatible bubbles can be applied to the retina. The device includes a proximal end with a handle, a distal end, an internal fluid passage from the proximal end to the distal end, and a cannula connected to the distal end, the cannula having a distal tip and configured to generate biocompatible bubbles from a biocompatible adhesive when gas flows through the internal fluid passage, maintain the bubbles at the distal tip when the flow of gas through the internal fluid passage is stopped, and release the bubbles when the bubbles can touch the retina or when gas flows through the internal fluid passage again.

[0173] Some configurations relate to the use of a system, device, or kit for generating and / or applying biocompatible bubbles to the eye or retina, such as for the repair of the eye or retina. The use can include generating biocompatible bubbles using the system, device, or kit described herein, and / or applying biocompatible bubbles from the tip of the cannula to the eye or retina using the system, device, or kit described herein.

[0174] Some configurations relate to methods of repairing retinal tears. Some configurations of the method or use include generating a bioadhesive bubble that includes a substantially spherical film of a bioadhesive material encapsulating an expanding fluid using a system, device, or kit. Some configurations of the method or use include applying the bioadhesive bubble to an eye or retina from a system, device, or kit. Some configurations relate to methods of repairing a retinal tear or hole, the method including generating a bioadhesive bubble that includes a substantially spherical film of a bioadhesive material encapsulating an expanding fluid using a system, device, or kit, and applying the bioadhesive bubble to an eye or retina from a system, device, or kit. Some configurations include operation of a button on a handpiece of a device or system, or operation of a foot pedal, such as to open a valve, that enables the expanding fluid to flow through an expanding fluid passage of the handpiece and / or a fluid passage of a cannula.

[0175] Some of the devices disclosed herein significantly improve their ability when used for either the function of converting a cohesive liquid into bubbles having a surface area and control and precision of placement far greater than the original bubble-free cohesive liquid and closing gaps within tissue, or the function of reducing the incidence of PVR by blocking the detachment of RPE cells into the vitreous cavity.

[0176] The devices and methods disclosed herein can be used to close various discontinuous and continuous structures including, but not limited to, retinal tears and holes, macular holes, macular pits, posterior capsule ruptures of the lens, scleral tears, corneal tears, corneal abrasions, conjunctival tears, retinal pigment epithelial tears, and for non-ophthalmic medical uses include, but are not limited to, skin tears, mucosal tears regardless of location, and include, but are not limited to, delivery of substances having no other function.

[0177] The substances delivered by any of the devices disclosed herein can be used for delivering the substances through the vitreous body. For vitreous body use, delivery via the device can use a cutting operation that cuts cohesive / adhesive substances once the substance has been advanced to the target location. The excess can be removable by vitreous cutter and / or aspiration. Vitreous delivery can be utilized in an air-filled eye to avoid adhesive substances floating in non-target eye structures such as the lens / IOL / ciliary body part / corneal endothelium, which may cause occlusion of the visual field through the lens / IOL or obstruction of the inflow / outflow of aqueous humor.

[0178] Any of the devices disclosed herein can also be delivered by transscleral delivery, which can include delivery of substances to retinal breaks through the subretinal space. Once the substance has been applied to the retina after being delivered through the tapered end or needle of the device, the substance can be detached when the needle is withdrawn from the sclera. The substance can act as a buffer solution to prevent the retina from fitting into the scleral defect by a cannula, a needle, or a device utilized to cross the scleral and choroidal tissues.

[0179] Any configuration of the delivery devices disclosed herein can have single, double, or triple bores. A double-bore device can include one bore for delivering the substance and a second bore for refluxing the intraocular fluid out of the eye as the IOP increases. One of the bores can include an optical fiber that can be used for illumination. One of the bores can include a fiber that can deliver laser light. One of the bores can include a fiber that delivers heat or some other energy source used to cure the injected substance. A triple-bore device can include one bore for delivering the substance, one bore for passing a gas used to generate bubbles or a film of an adhesive substance, and a third bore for refluxing the intraocular fluid out of the eye as the TOP increases.

[0180] Figures 38 - 42 show schematic views of examples of the distal ends or tips of various configurations 900, 910 of the device. In any configuration, a single or double compartment syringe can be attached to a distal tip having a double compartment that matches when connected. Referring to FIGS. 40 and 41, the double isolated air columns can optionally compress the contents within any two optional distal tip compartments 912, 914. Some configurations include a handle such as a syringe - shaped handle.

[0181] As shown in FIGS. 38 - 42, there may be an internal aspect of the distal tip, which may be expanded to provide support and stability to the tip's bubbles. The tip can include an outer hollow wall and a material such as air or gas in an inner or internal aspect. The tip can have one or more openings (such as passages) 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 passes. A film of a substance can be created across the opening of the distal end or distal tip. The hollow wall of the cannula can be of various volumes, and the relative volumes of the hollow wall and the central core can vary. Some configurations include a double plunger for the central core and / or an outer cannula of the hollow wall. The double plunger can operate and / or advance together with or independently of the cannula or other components of the device. The components can be of various lengths, widths, and volumes.

[0182] 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 syringe-shaped device that is handheld and generates bubbles in a controlled manner, one bubble at a time; the ability to generate bubbles from liquids of various compositions and viscosities; the ability to generate bubbles from gels of various compositions and viscosities; the ability to maintain a reservoir of the substance in which bubbles are generated at a temperature within a specific range depending on the substance used; a temperature-controlled chamber within the device where a temperature control mechanism can be optionally added to the device but can be specifically calibrated for the substance being used in the task at hand so that the temperature control can be turned on / off; a power source comprising one or more batteries, where the batteries can optionally be incorporated into the handheld device; a power source comprising an electrical cord for connection to a vitrectomy power source or an external power source; one or more color-coded devices having colors correlated to specific substance compositions, where different substance compositions can optionally have specific optimal temperatures or temperature ranges for optimizing bubble generation; a device configured to enable control and variation of the bubble wall thickness based on the temperature of the substance during bubble generation, using, for example, one or more of a heater and / or a cooler; a device configured to enable control and variation of the bubble wall thickness based on the viscosity of the substance during bubble generation; a device configured to vary the bubble wall thickness by the various dimensions of a specific device opening and the amount of air or gas passing through the substance composition during the bubble generation process, including, for example, a kit or system, where the kit or system has a plurality of different devices, each device having a different distal tip opening that generates bubbles having a consistent size / diameter and a wall thickness different from the other devices of the kit; and a device having the ability to control an adjustable opening and the volume of air injected to form bubbles, providing the ability to customize the size of the bubbles and the thickness of the bubble walls according to the clinical situation, for example, in a retinal detachment application having a plurality of retinal tears of various sizes that each have a substantially the same bubble wall thickness but where different bubble sizes may be desired to be used.

[0183] In any configuration disclosed herein, the device can also be configured to have one or more of the following features, characteristics, capabilities, or details. Using one device to close a retinal tear and then closing the scleral external opening (i.e., sclerotomy) into which the cannula was inserted at the end of the case, where the surgeon may desire access to a larger bubble wall thickness due to the greater tensile forces associated with the scleral wound compared to the retinal tear. Variations of the device for generating bubbles of various sizes of various diameters, for example, ranging from 0.5 mm to 15 mm, and other ranges of bubble diameters are, for example, 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 number in between; the ability to release bubbles and also generate additional bubbles that can also be released, which can be done to avoid clogging of the cannula / device tip; a mechanism for releasing bubbles from the cannula / device tip, which mechanism can include one or more of heating the tip to melt or heat a substance, cooling the tip to break up a substance, and a device having a cutting or wiping mechanism at the tip; a device including an optical fiber used to transmit light for curing the substance used in the balloon, where the optical fiber may be fixed or may be movable to advance from the tip of the device, the optical fiber may advance into the interior of the bubble to bring light close to the portion of the bubble in contact with the retina, sclera, or other targeted human tissue, and / or the optical fiber may be housed in a different bore of the cannula and used to cure the substance from the outside of the balloon; a device that may include a cannula and an associated distal tip separate from the bubble generating portion of the device, allowing for the dropping or spraying of a liquid or gel or other substance onto the surface of the retina prior to the application of the bubble, the purpose of this other substance being to deposit a substance of a specific composition that reacts with the bubble substance, for example, to cause a change in the consistency of both substances from liquid to solid.

[0184] Any of the configurations of the devices and systems disclosed herein can be used to apply an adhesive to a biological or non-biological surface or object, which can include a medical scaffold, patch, cover, graft, or other object or instrument used for medical and non-medical applications. For example, without limitation, FIG. 43 shows a non-limiting example of a system 1000 having a substance supply device 1001 and an applicator device 1002. The substance supply device 1001 can include, without limitation, any combination of devices, configurations, and / or components disclosed elsewhere herein for providing a substance to a surface or object, including, for example, devices 100, 200, 250, 350, etc. The substance supply device 1001 can be advanced through a first introducer cannula or sheath to a desired space or location (such as, without limitation, an air-filled eye cavity), and the applicator device 1002 can be advanced through a second introducer cannula or sheath to the eye cavity. The substance supply device 1001 can be used to apply a substance that can include a bioadhesive to a desired surface of the applicator device 1002.

[0185] Figures 44 and 45 respectively show a top view and a side view of an example of an applicator device 1002 that can be used in conjunction with any of the devices disclosed herein for supplying a substance to a surface or an object. As will be described below, in any configuration, the applicator device can be used to receive a substance on its applicator portion for applying the substance to a tissue surface or an object, thereby supporting the object (such as a patch) and delivering the object to a desired location. For example, without limitation, the applicator device can be configured to support a patch, a tissue cover, a tissue graft, a tissue scaffold, or others (collectively referred to herein as a patch), whereby a surgeon or a user can use the applicator device 1002 to place 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 substances, or an adhesive can be loaded into the surgical site or space using the substance supply device 1001. Thereafter, when the patch is loaded with a desired amount of adhesive, the patch can be applied to a desired object or tissue surface. Further, without limitation, the applicator device 1002 can be used to hold the patch in a desired application position, enabling the adhesive to adhere or cure sufficiently and thus bond to the target tissue.

[0186] Referring to FIGS. 43 and 44, the applicator device 1002 can include a cannula or outer sleeve 1003 (also referred to herein as an elongated body or outer sheath), an inner sleeve or rod 1005 that can optionally have a solid cross-section or a conduit or passage 1007 extending therethrough, and an applicator tip 1006 coupled to the inner rod 1005. The outer sleeve 1003 can optionally be configured to provide additional rigidity and operability to at least a portion of the inner rod 1005 and the applicator tip 1006 to facilitate or improve the control of the user of the applicator device 1002 during the application of the substance 1001.

[0187] 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 is operable by the surgeon or user of the device and can move the applicator tip 1006 forward, backward, rotationally, and in other ways.

[0188] The cannula can optionally be flexible, semi-rigid, or rigid and can be formed from any suitable material including metal alloys, polymeric materials, and the like. The system can optionally be configured to not have an outer sleeve 1003, and the inner rod 1005 and the applicator tip 1006 are sufficiently rigid and operable without the need for an outer sleeve 1003.

[0189] In any configuration disclosed herein, after the cannula 1003 has advanced to the target position, it is not necessary to advance the applicator tip 1006 to the proximal end of the cannula 1003, and the size of the applicator device 1002 that advances to the target position is defined by the size of the cannula 1003 rather than the larger applicator tip 1006, so that the applicator tip 1006 and / or other components can be pre-loaded into the cannula or the outer sleeve 1003, thereby improving the operability of the device and reducing the risk of patient injury. Optionally, the applicator device 1002 can be configured such that after the cannula 1003 has advanced to the target position, the applicator tip 1006 advances to the proximal end of the cannula 1003. The proximal end of the cannula 1003 can 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 crushing and / or rounding or bending of the applicator portion 1010 for insertion into the cannula 1003.

[0190] As described above, when the applicator tip 1006 is in the first state or the 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 defined by the outer sleeve 1003 such that the force required is less, and as a result, the risk of trauma to the tissue is less and it can advance through the opening in the tissue surface. Some configurations of the applicator device 1002 can be configured such that, as best shown in FIG. 45, when the applicator portion 1010 is retracted into or disposed within the outer sleeve 1003, the applicator portion 1010 is biased to assume a curved, bent, folded, or rounded shape that fits within the inner space of the outer sleeve 1003.

[0191] Referring to FIG. 45, when the applicator portion 1010 has the inner rod 1005 and the applicator tip 1006 retracted into the outer sleeve 1003 from the second state to the first state or the retracted state, the applicator device 1002 can be configured to bias the applicator portion 1010 so that the applicator tip 1006 can be drawn through an opening in the tissue with the applicator tip 1006 retracted into the outer sleeve 1003, or otherwise configured to crush into a more compact or narrower shape or state as shown in FIG. 45. As shown and described, the applicator portion 1010 can have a width W that is greater than the width of the outer sleeve 1003. Since the applicator portion 1010 is configured or biased to move to a more compact profile when retracted into the cannula 1003, retracting the applicator portion 1010 into the outer sleeve 1003 as shown in FIG. 45 can reduce the size of the distal portion of the applicator device 1002 to the size of the outer sleeve 1003, thereby reducing trauma to the patient during device retraction. In any configuration, the applicator portion 1010 can be folded, rounded, compressed, squeezed, narrowed, or otherwise configured to have any feature that allows the width W or size to be reduced when retracted into the outer sleeve, or can be made of any material.

[0192] The applicator portion 1010 can have or define a first width when the applicator portion 1010 is in a first position (when 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 (when the applicator tip extends beyond the opening of the distal end 1003a of the outer sleeve 1003). The second width of the applicator portion 1010 can be substantially greater 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 the first width of the applicator portion 1010, or about 2 times (or, optionally, less) to about 8 times (or, optionally, more) the first width of the applicator portion 1010, or about 3 times to about 6 times the first width of the applicator portion 1010.

[0193] The inner rod 1005 can advance relative to the outer sleeve 1003 such that the distal end portion 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 elongate portion 1008 and an applicator portion 1010. The elongate portion 1008 of the applicator tip 1006 can optionally have a passageway 1012 that extends therethrough from the proximal end 1008a to the distal end 1008b of the elongate portion 1008. The passageway 1012 can be in fluid communication, in an operative state, at the proximal end 1008a of the elongate portion 1008, if any, with the passageway 1007 of the inner rod 1005. One or optionally a plurality of openings 1014 can be formed, optionally through the first surface 1011 of the applicator portion 1010, and the openings or orifices 1014 are in fluid communication with the passageway 1012. The openings 1014 can be used to convey a suction source or negative or positive pressure or an air stream to any object that is adjacent to or in contact with the applicator portion 1010. The suction source can communicate with the openings 1014 through the passageways 1007 and 1012 from the proximal end of the device, for example, via a handle coupled to the outer sleeve of the device. For example, without limitation, a suction force can be applied through the openings to selectively attract and secure any desired object, including one or more bubbles containing a substance (optionally with a gentle suction force to avoid bursting of the bubbles), a patch, a tissue cover, a scaffold, or other object, to the first surface 1011 of the applicator portion 1010. For example, without limitation, a gentle suction force can be applied through the openings 1014 to attract and secure a bubble containing a substance to the first surface 1011 of the applicator portion 1010.

[0194] Thereafter, the applicator portion 1010 can move the bubble to a desired location, such as a tissue defect within the surgical air cavity in the eye. The substance can be released from the applicator portion 1010 by reducing the suction force or negative pressure provided through the opening 1014, by pressing and / or manipulating the applicator portion 1010 against the target surface, and / or by applying a positive pressure, such as optionally a short burst or positive pressure, through the opening. To facilitate the release of the bubble, the supply of positive pressure (e.g., by providing a positive air flow through the opening 1014) can be used.

[0195] In another non-limiting example, negative pressure can be used to selectively secure a patch or any other instrument to the first surface 1011 of the applicator portion 1010. For example, as shown in FIG. 46, a suction source can be applied through the opening 1014 to the patch or other medical instrument 1025 to selectively and releasably hold the patch 1025 against the first surface 1011 of the applicator portion 1010. Thereafter, the patch 1025 can be delivered to the desired location and advanced to contact the target tissue surface by advancing the applicator device 1002 to the target location. When the desired location of the patch 1025 is achieved and the patch is optionally held in a position long enough to secure the patch to the target tissue surface, the negative pressure can be reduced and the patch can be released from the applicator portion 1010. To facilitate the release of the patch, positive pressure or an air flow can be optionally provided through the opening.

[0196] Further, referring to FIG. 46, a suction source can be applied through the opening 1014 to the patch or other medical device 1025 to selectively and releasably hold the patch 1025 against the first surface 1011 of the applicator portion 1010. Thereafter, a substance supply device 1001 (which can be any component or detail of any configuration of the bubble, loop, or other substance supply devices disclosed herein, or can have them) can provide a layer of bubbles 146 or substance 105 on the surface of the patch 1025. The substance 105 can be a bioadhesive. The bubbles 146 and / or the substance 105 can be applied to the patch as described above for the device 130 of FIGS. 4A-4D. After the substance 105 is applied to the patch, as shown in FIG. 47, the patch 1025 can be delivered to the desired position, and by advancing the applicator device 1002 to the target position, the adhesive-coated surface of the patch 1025 can be advanced to contact the target tissue surface. When the desired position of the patch 1025 is achieved and the patch is optionally held in a position long enough to fix the patch to the target tissue surface, the negative pressure can be reduced and the patch can be released from the applicator portion 1010. In any configuration, the applicator portion 1010 can be biased and configured to be in a folded or bent shape such that when the applicator portion 1010 is drawn into the cannula 1003, the interaction with the distal end of the cannula 1003 allows the applicator portion 1010 to be fully drawn into the cannula.

[0197] In other configurations, the applicator portion 1010 is solid and may not have an opening or orifice therein. Further, the applicator tip 1006 can have a planar shape, a curved shape as shown in FIG. 46, etc. In other configurations, clips, tabs, recesses, ridges or protrusions, or other features can be used to selectively and releasably hold a patch or other medical device on the first surface 1011 of the applicator portion 1010. In other configurations, the applicator portion 1010 and the applicator device 1002 can be configured such that a patch, cover, or other medical device can be freely placed on the first surface 1011 of the applicator portion 1010. In any configuration, the patch may be pre-loaded into the cannula 1002, and 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, and the patch 1025 can be wound up relative to the surface 1011 of the applicator portion 1010 and still be held against the first surface 1011 of the applicator portion 1010.

[0198] In any configuration, the patch can be secured to the proximal end of the patch using end grasping forceps extendable from the cannula. The forceps can self-expand such that when the cannula retracts relative to the forceps, or the forceps advance distally relative to the distal end of the cannula, the forceps open to release the grip on the patch. In this configuration, the patch can be pre-loaded inside the distal end of the cannula with at least a portion of the patch being grasped by the forceps. Since the forceps are constrained by the cannula, the forceps remain grasping the patch until the forceps advance distally from the cannula or the cannula is pulled proximally relative to the forceps. For example, when the forceps advance distally relative to the cannula, the patch can be moved beyond the distal end of the cannula and opened, deployed, or expanded to a relaxed expanded state while the forceps are still sufficiently constrained in the closed position by the cannula such that the forceps continue to grasp the patch. In this state and position, a substance such as a biologic adhesive can be applied to the desired surface of the open or relaxed patch using any of the substance applicator devices disclosed herein, for example, but not limited to, device 130. The substance can be applied as a bubble, a plurality of bubbles, etc. The substance applicator can also optionally be used to spread the substance on 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 forms a sufficient bond between the patch and the tissue surface. Thereafter, the forceps can be further expanded to release the grasp of the forceps on the patch by advancing the forceps distally relative to the cannula and / or by retracting the cannula by means such as a button or slide action to allow the forceps to expand. The forceps can then be withdrawn into the cannula and removed from the surgical site.

[0199] The forceps or other grasping means disclosed in any configuration of this specification can be or can include the DSP forceps of ALCON Revolution or the DSP forceps of GRIESHABER. For example, such forceps can be used to grasp and / or manipulate a patch used in any configuration disclosed herein.

[0200] The patch can also be released from the applicator portion using any mechanical component that includes an end-grasping forceps and a button that the surgeon or user can advance to advance the attached patch and / or patch material. When the forceps are loaded in the passive open position, the forceps can be biased or configured to open or return to an open or relaxed state as the forceps extend beyond the distal tip of the cannula.

[0201] In another method, the same internal end-grasping forceps can pinch the patch at its tip, but the button can be used in the reverse way to pull the cannula back from around the end-grasping forceps and the 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 the patch, thereby avoiding hitting the patch against the retina, which can occur if the surgeon does not counteract by slowly pulling the cannula away from the retina as the tip advances. When the cannula is fully retracted proximal to the tip of the end-grasping forceps, the forceps are biased to open passively and release the patch and / or spatula or both.

[0202] Furthermore, some configurations can have a selectively severable connector 1022 that couples the proximal end 1008a of the elongated body 1008 to the distal end 1005b of the inner rod 1005. In some configurations, thus, the applicator tip 1006, which includes at least the applicator portion 1010, can be released from the inner rod 1005 by disengaging the connector 1022. Thereby, the applicator tip 1006 can be removed from the device and left in place within the patient's body. In this configuration, the applicator portion 1010 can be an essentially defect patch or cover. The applicator tip 1006 can be made from any suitable material, including any suitable bioabsorbable or biocompatible material.

[0203] In any configuration of an embodiment of the applicator device 1002 or any substance delivery device disclosed herein, the handle, cannula or outer sheath 1003, inner sheath 1005, or other rigid or semi-rigid component can be made from or can include any suitable plastic material, patch material, metal, polyvinyl chloride, glass, acrylic, carbon fiber, and / or any combination of the foregoing. In some configurations, the cannula tip plug or protective tip cover can include plastic, metal, polyvinyl chloride, glass, acrylic, carbon fiber, rubber (e.g., but not limited to, silicone), and / or any combination of the foregoing.

[0204] Figures 48 and 49 respectively show a top view and a side view of an embodiment of a device 2100 (also referred to herein as a delivery device) for applying a substance 2101 to the surface of an object. In some embodiments, the device 2100 can include a cannula or outer sleeve 2102 (also referred to herein as an elongated body or outer sheath), an inner sleeve 2104 (also referred to herein as an inner cannula) having an internal conduit or passage 2105 through which the substance 2101 can be advanced, and an applicator 2106 (also referred to herein as an applicator tip) coupled to the inner sleeve 2104. The outer sleeve 2102 can be configured to provide additional rigidity and operability to at least a portion of the inner sleeve 2104 and the applicator 2106 so as to facilitate or improve control by a user of the device 2100 during application of the substance 2101.

[0205] The inner sleeve 2104 can have a proximal end 2104a (not shown) and a distal end 2104b. The passage 2105 can extend from the proximal end 2104a to the distal end 2104b of the inner sleeve 2104. As shown, the applicator 2106 can be coupled to the distal end 2104b of the inner sleeve 2104.

[0206] The cannula can optionally be flexible, semi-rigid, or rigid and can be formed from any suitable material including, for example, a metal alloy, a polymeric material, and the like. The system can optionally be configured to not have an outer sleeve 2102, and the inner sleeve 2104 and the applicator 2106 can be sufficiently rigid and operable without the need for an outer sleeve 2102.

[0207] In any of the embodiments disclosed herein, the applicator 2106 and / or other components can be pre-loaded onto the cannula or outer sleeve 2102 such that after the cannula 2102 has advanced to the target location, there is no need for the applicator 2106 to advance to the proximal end of the cannula 2102. Optionally, the device 2100 can be configured such that after the cannula 2102 has advanced to the target location, the applicator 2106 advances to the proximal end of the cannula 2102. The proximal end of the cannula 2102 can be tapered to facilitate insertion of the applicator portion 2110 into the cannula 2102 and / or to facilitate crushing and / or rounding of the applicator portion 2110 for insertion into the cannula 2102.

[0208] In any embodiment of the device 2100, the handle, cannula or outer sheath 2102, inner sheath 2104, or other rigid or semi-rigid component can be made of or include any suitable plastic material, metal, polyvinyl chloride, glass, acrylic, carbon fiber, and / or any combination of the foregoing. In some embodiments, the cannula tip plug or protective tip cover can include plastic, metal, polyvinyl chloride, glass, acrylic, carbon fiber, rubber (e.g., but not limited to, silicon), and / or any combination of the foregoing.

[0209] The distal end portion 2106a of the applicator 2106 can extend from the distal end 2102a of the cannula 2102. In any embodiment, the applicator 2106 can have an elongate portion 2108 and an applicator portion 2110. The elongate portion 2108 of the applicator 2106 can optionally have a passageway 2112 extending therethrough from the proximal end 2108a to the distal end 2108b of the elongate portion 2108. The passageway 2112 can be in fluid communication with the passageway 2105 of the inner sleeve 2104 at the proximal end 2108a of the passageway 2108 in an operative state. An opening or orifice 2114 can be disposed at the distal end 2108b of the body 2108 and can be in fluid communication with the passageway 2112. Some embodiments can have a connector 2122 coupling the proximal end 2108a of the body 2108 to the distal end 2104b of the inner sleeve 2104. In this embodiment, the substance 2101 can advance through the passageway 2105 of the inner sleeve 2104, through the connector 2122, through the passageway 2112 extending through the elongate portion 2108 of the applicator 2106, and can emerge onto the first surface 2110a of the applicator portion 2110 of the applicator 2106 through the opening 2114.

[0210] In another embodiment, as shown in FIGS. 57 and 58, the device 2300 can have an outer sleeve 2302 and an applicator portion 2310, and an additional movable cannula 2338 having a passageway 2340 disposed within the outer sleeve or cannula 2302. The passageway 2340 can optionally provide a passageway for the transfer or delivery of a substance 2101 (which can optionally be the above-described substance, or any other embodiment disclosed herein, or any other desired material) to various portions of the applicator portion 2310. As will be described, the movable cannula 2338 (also referred to herein as a filling cannula or a refill cannula) can be configured to be movable relative to at least a portion of the outer sleeve 2302 and / or the applicator 2306 from at least a first position as shown in FIG. 57 to a second position as shown in FIG. 58. The applicator 2306 and the applicator portion 2310 can have any of the features, materials, or other details of any of the other applicators and applicator portions disclosed herein, including but not limited to, the applicator 2106 and the applicator portion 2110.

[0211] In any of the embodiments disclosed herein, the device can have an outer sleeve and an applicator portion, and an additional fixed conduit or cannula (e.g., a fixed version of cannula 2338) having a passageway within the outer sleeve or cannula. The conduit or cannula can provide a passageway for the transfer or delivery of a substance 2101 to the applicator portion 2310, which can optionally be the substance described above, or any other embodiment disclosed herein, or any other desired material. For example, without limitation, the substance can be exuded through an opening at the distal end of the conduit or cannula into the applicator portion. Further, in some embodiments of the device, the substance can be configured to first exude at the distal or leading edge of the applicator portion and then along the length of the applicator portion as the applicator portion extends distally when the substance is continuously injected and exuded through an opening at the distal end of the substance supply conduit or passageway. In some embodiments, the distal end of the substance supply conduit or cannula can be configured to exude the substance over a broad band on the applicator portion via a plurality of openings, a manifold, or a wide slot opening, etc. In some embodiments, the only movable or extendable component of the device or the distal end portion of the device can be the applicator and the applicator portion, which can be integrally connected.

[0212] In practice, after the applicator 2306 has advanced to its full extended position, the cannula 2338 can be advanced, for example but not limited to, to the distal portion of the applicator portion 2310, i.e., to the first position shown in FIG. 57. The substance 2101 can first be advanced through the passage 2340 onto the distal portion 2310a of the applicator portion 2310. Then, as the cannula 2338 retracts towards a second position (as shown in FIG. 58), which can optionally be done slowly for better control and coverage of the applicator portion 2310, the user can continue to discharge the substance onto the central and / or proximal portions of the applicator portion 2310. In this configuration, the user, who can optionally be a surgeon or other medical practitioner, can achieve a more uniform consistency and distribution of the substance over some or all of the portions (distal, intermediate, and proximal portions) of the applicator portion 2310 using the movable cannula. In some embodiments, the movable cannula can enable a more uniform consistency and distribution of the substance over some or all of the portions (distal, intermediate, and proximal portions) of the applicator portion 2310 as compared to a fixed passage or cannula.

[0213] Furthermore, in any of the embodiments disclosed herein, the device can have a first or fixed inner cannula (such as cannula 2104) and a movable cannula surrounding the outer surface of the inner cannula 2104, which can advance through a passage passing through the distal tip as described above. In these embodiments, two passages can be used to supply the substance to the applicator portion. The movable passage, which can optionally be an additional cannula or sleeve, can be configured to be retractable and extendable relative to the inner cannula 2104, the passage through the applicator, and / or the applicator portion.

[0214] After the substance 2101 is advanced onto the first surface of the applicator portion 2110 (or 2310) of the applicator 2106, the user can apply the substance 2101 to the desired surface. For example, in an application where the device 2100 is used for applying a therapeutic substance to the eye surface, after a surgeon or medical practitioner uses the applicator portion 2110 to apply the substance 2101 to the target portion of the eye surface, the substance 2101 can be advanced onto the first surface 2110a of the applicator portion 2110 of the applicator 2106 located there. In any embodiment, the applicator 2106 can be made or configured to be flexible and conformable to reduce the risk of puncture or other damage to the tissue to which the substance 2101 is applied. In some embodiments, the applicator 2106 can be made from a medical grade silicone material, one or more biodegradable materials, one or more different types of alloys including stainless steel and nitinol, or any other suitable rubber or other flexible polymer material. In any embodiment, the applicator portion 2110 can be made from a material designed to enhance the thermal conductivity of the applicator portion 2110, i.e., a material having enhanced thermal conductivity characteristics that better enable the applicator portion 2110 to transfer heat or cooling.

[0215] Any embodiment of the device 2100 can optionally have a distal tip (not shown) coupled to the distal end 2102a of the outer sheath or cannula 2102. The distal tip can optionally have a conical or tapered profile and can be made from a flexible material such as silicone or other suitable polymer, an alloy such as stainless steel or nitinol. Alternatively, in other embodiments, the distal end 2102a of the cannula 2102 can have an angled or beveled end face configured to facilitate the distal end 2102a advancing through an opening in the tissue surface or other opening.

[0216] In other embodiments, the distal end 2102a may be pointed and sharp like a hollow needle tip to allow insertion through tissue, such as through the sclera, to access the subretinal space. Optionally, the device of any of the embodiments disclosed herein can have a distal tip portion distal to a cannula 2102 that includes a softer material such as flexible silicone. The softer tip portion can be used in some applications to reduce the risk of trauma to the tissue surface. Further, in any of the embodiments, a soft tip can be used to gently touch the surface of the tissue to gently spread or move a substance, or to remove a substance from the tissue.

[0217] The device 2100 can also optionally have a removable distal plug or tip cover that can be removably coupled to the distal end 2102b of the cannula 2102 and / or the distal tip of the device 2100. The distal plug or tip cover can provide a seal with the passage through the cannula 2102, can be removed prior to advancing the device into the target tissue region to provide a seal of the device to maintain sterility within the device, and can also provide a seal for sealing the passage through the cannula in a device pre-filled with a substance.

[0218] Further, as most clearly shown in FIG. 49, some embodiments of the applicator 2106 can have a profile that is curved in at least one of the length direction L (identified in FIG. 49) and the width direction W (identified in FIG. 48). For example, without limitation, some embodiments of the applicator portion 2110 can have a profile that is curved or slightly curved in both the longitudinal and width directions, and the curved profile is sized and configured to be similar to the curvature of the target tissue surface (optionally, the surface of the retina of a human eye or other eye surface, the eye of an animal or organism, etc.) and / or to better hold the desired substance on the applicator portion. In other embodiments, the applicator portion 2110 can be configured to improve the ability of the applicator portion 2110 to hold the substance 2101 on the applicator portion 2110, particularly when the applicator portion 2110 is rotated, tilted, and / or turned upside down. In other embodiments, the applicator portion 2110 can have a substantially flat profile or shape, or any other desired profile or shape.

[0219] The cannula 2102 and / or cannula (or inner sleeve) 2104 of any of the embodiments disclosed herein can optionally have a tubular shape and size of from about 25 gauge (0.455 mm size), or 27 gauge (0.361 mm size), or about 28 gauge (0.33 mm size) or less to or about 20 gauge (0.813 mm) or more, or 27 gauge (0.361 mm size) to or about 24 gauge (0.511 mm), or any value within these ranges. Optionally, in other embodiments, larger or smaller cannulas can be used for the inner and / or outer cannulas or sleeves.

[0220] In any embodiment, the cannula, cannula base, cannula body, and / or cannula tip can have a cross-sectional diameter of 0.1 - 0.5 mm, 0.5 - 1 mm, 1 - 2 mm, 2 - 3 mm, 3 - 4 mm, 4 - 5 mm, 5 - 6 mm, 6 - 7 mm, 7 - 8 mm, 8 - 9 mm, or 9 - 10 mm. Optionally, the cannula, cannula base, cannula body, cannula tip, and / or cannula outlet port can have a length of 0.1 - 0.5 mm, 0.5 - 1 mm, 1 - 2 mm, 2 - 3 mm, 3 - 4 mm, 4 - 5 mm, 5 - 6 mm, 6 - 7 mm, 7 - 8 mm, 8 - 9 mm, 9 - 10 mm, 10 - 20 mm, 20 - 30 mm, 30 - 40 mm, or 40 - 50 mm. Further, the cannula, cannula base, cannula body, cannula tip, and / or cannula outlet port can have an outer diameter, inner diameter, and width between the inner and outer diameters of 0.01 - 0.05 mm, 0.05 - 0.1 mm, 0.1 - 0.5 mm, 0.5 - 1 mm, 1 - 2 mm, 2 - 3 mm, 3 - 4 mm, 4 - 5 mm, 5 - 6 mm, 6 - 7 mm, 7 - 8 mm, 8 - 9 mm, 9 - 10 mm, 10 - 20 mm, 20 - 30 mm, 30 - 40 mm, or 40 - 50 mm.

[0221] For other uses than ophthalmic uses, the cannula 2102 can optionally have a tubular shape and a cross-sectional size or inner diameter of 10 mm or about 10 mm - 200 mm or about 200 mm or more, or 40 mm or about 40 mm - 80 mm or about 80 mm.

[0222] Some embodiments of the devices and methods disclosed herein can be configured to deliver and apply various materials or substances of various viscosities to a target tissue or surface. Examples of substances that can be used with any of the devices, systems, and methods disclosed herein include, but are not limited to, adhesives, bioadhesives, gels, hydrogels, thick or semi-liquid therapeutic substances, bilayer hydrogels, non-solids, polyethylene glycol solutions, trillidinamine solutions, polymeric hydrogels, thermoresponsive gels, and any combination of the foregoing. Examples of bioadhesive substances that can be used in any of the embodiments disclosed herein include, but are not limited to, ReSure™ sealant, polyethylene glycol hydrogels and other hydrogels, cyanoacrylate, fibrin glue, polyethylene glycol solutions, trillidinamine solutions, glycoproteins, elastin proteins, carbohydrates, mucopolysaccharides, etc. In some embodiments of the system or device, the bioadhesive material includes a resin. UV or photoactivated bioadhesives can also optionally be used with any of the device embodiments disclosed herein. In some such embodiments, the system, kit, or device can incorporate a light or optical fiber for activating the bioadhesive material.

[0223] Thermoactivated bioadhesives can also optionally be used with any of the device embodiments disclosed herein. In some such embodiments, the system, kit, or device can incorporate a material that conducts heat to activate the bioadhesive material.

[0224] In some embodiments, the substance can include an adhesive or a bioadhesive. As used herein, the term "adhesive" is given its ordinary meaning and is also intended to encompass bioadhesives. Examples of adhesives that can be used in any of the embodiments disclosed herein include, but are not limited to, polyvinyl acetate, glue, aliphatic, cyanoacrylate, epoxy, polyurethane glue, and contact cement. Examples of bioadhesives include, but are not limited to. In some embodiments, the adhesive is a biomimetic material. In some embodiments, the adhesive is not a bioadhesive.

[0225] Any of the embodiments disclosed herein can also be configured to use one or more substances that polymerize when the temperature of the substance reaches a threshold or range of values, such as, but not limited to, normal body temperature, or 80°F or about 80°F to 100°F or about 100°F or more, or 90°F or about 90°F to 100°F or about 100°F or more, or 95°F or about 95°F to 100°F or about 100°F or more, or any value within these ranges. Further, any of the embodiments can be used to apply a low-temperature curable substance to the tissue surface, i.e., a substance that polymerizes when the temperature of the substance reaches a threshold or range of values, such as, but not limited to, 10°F lower than body temperature, or 70°F or about 70°F or less to 90°F or about 90°F, or 80°F or about 80°F to 90°F or about 90°F, or any value within these ranges.

[0226] Any embodiment disclosed herein can also be configured to polymerize with activation by light of any number of various wavelengths or to use one or more substances that are activated by light. The activation light may be provided by a special applicator within or separate from the material delivery device. Suitable substances that can be used typically include substances used on or approved for use on the ocular surface, including the subretinal space, the vitreous cavity, or the conjunctiva superior or inferior, and substances that can be used to close gaps within tissue.

[0227] In any embodiment, the applicator portion 2110 can be retracted within the outer sleeve 2102, and is sufficiently flexible to crush in the width direction W, or otherwise structurally biased, so as to minimize the force exerted on the more rigid material and the resulting trauma. FIGS. 50 and 51 respectively show side and end views of an embodiment of the device 2100 shown in FIG. 48, showing the device in a first or retracted state in which the applicator portion 2110 is housed or retracted within the outer sleeve 2102. FIG. 52 is an end view of another embodiment of the device 2100 and the applicator portion 2110.

[0228] The inner sleeve 2104 and the applicator 2106 can optionally be advanced and retracted through the conduit or passageway 2103 of the outer sleeve 2102, such as between the first state shown in FIGS. 50-51 and the second or deployed state shown in FIGS. 48-49.

[0229] When the applicator 2106 is in the first state or the retracted state, the distal portion of the device 2100 can have a smaller profile or cross-sectional size defined by the outer sleeve 2102 such that less force is required and, as a result, the risk of trauma to the tissue is less and it can advance through the opening in the tissue surface. Some embodiments of the device 2100, as best shown in FIGS. 51 and 52, can be configured such that when the applicator portion 2110 is retracted into or disposed within the outer sleeve 2102, the applicator portion 2110 can take on a curved or helical shape so as to fit within the inner space of the outer sleeve, thereby forming a space 2130 confined by the first surface 2110a of the applicator portion 2110.

[0230] Referring to FIG. 52, the applicator portion 2110 can be biased so that when the inner sleeve 2104 and the applicator 2106 are all pulled back into the outer sleeve 2102 from the second state to the first state or the retracted state, the applicator 2106 is in a state of being pulled into the outer sleeve 2102 and the device 2100 can be pulled through an opening in the tissue, or otherwise can be configured to collapse into a more compact or narrower shape or state as shown and described in FIG. 52. As shown and described, the applicator portion 2110 can have a width W that is greater than the width of the outer sleeve 2102. Since the applicator portion 2110 is configured or biased to move to a more compact profile, by pulling the applicator portion 2110 into the outer sleeve 2102 as shown in FIGS. 51 and 52, the size of the distal portion of the device 2100 can be reduced to the size of the outer sleeve 2102. Thereby, the trauma to the tissue when the device 2100 is pulled through any opening in the tissue, if any, can be reduced. In any embodiment, the applicator portion 2110 can have any feature that allows it to be folded, rounded, compressed, squeezed, narrowed, or otherwise reduced in width W or size so as to fit within the outer sleeve, or can be configured to be made of any material.

[0231] The applicator portion 2110 can have or define a first width when the applicator portion 2110 is in the first position (when the applicator portion 2110 is contained within the outer sleeve 2102) and a second width when the applicator portion 2110 is in the second position (when the applicator tip extends beyond the opening of the distal end 2102a of the outer sleeve 2102). The second width of the applicator portion 2110 can be substantially greater than the first width of the applicator portion 2110. In any of the embodiments disclosed herein, the second width of the applicator portion 2110 can be about 5 times the first width of the applicator portion 2110, or 2 times or about 2 times (or, optionally, less) to 8 times or about 8 times (or, optionally, more) the first width of the applicator portion 2110, or 3 times or about 3 times to 6 times or about 6 times the first width of the applicator portion 2110.

[0232] In any of the embodiments disclosed herein, the second width of the applicator portion 2110 can be 2 mm, or about 2 mm, or 3 mm, or about 3 mm, or 4 mm, or about 4 mm, or 1.5 mm or about 1.5 mm (or less) to 6 mm or about 6 mm (or greater), or 2 mm or about 2 mm to 4 mm or about 4 mm, or 2 mm or about 2 mm to 3 mm or about 3 mm, or any size within these ranges, or from any size within these ranges and to any size within these ranges. In other embodiments where the device can be used on non-ocular tissue, the second width can be 2 times greater than, or 3 times greater than, the values or ranges listed above, or any value or from any value to any value.

[0233] The applicator portion 2110 can be made of a solid non-porous material. Alternatively, the applicator portion 2110 can be made of a porous material having a plurality of openings or slits, or any combination thereof, such as a sieve or a swatcher. The openings or slits can optionally be of variable size and / or variable dimensions.

[0234] A further advantage of withdrawing the applicator portion 2110 within the sleeve 2102 is that as the material 2101 advances through the passages formed in the inner sleeve 2104 and the applicator 2106, the material 2101 fills the space 2130 and thereby can contact and substantially cover the first surface 2110a of the applicator portion 2110. In this embodiment, to improve the coverage rate of the material 2101 on the first surface 2110a of the applicator portion 2110, the user can form a circular or roll shape of the applicator portion 2110, advance the material 2101, and optionally draw the applicator portion 2110 into the outer sleeve so as to form a space 2130 that can be substantially filled.

[0235] In any embodiment, the applicator portion 2110 can be retracted within the sleeve 2102 in the initial state of the device 2100. The material 2101 can optionally be pre-distributed within the passages 2105, 2112 and within the volume 2130 before the device 2100 advances to the target position. Further, the material can optionally be stored within the passages 2105, 2112 and within the volume 2130 before the device is used. In such embodiments, a thermoresponsive gel or other thermoactive material can be used to extend the shelf life of the pre-filled device and reduce the likelihood of the material curing during storage of the device or before application of the device. Heat from the patient's body or an additional heat source (e.g., but not limited to, a heat source integrated with or applied to the applicator portion 2110) can be used to activate the thermoresponsive material. In other embodiments, the user or surgeon can distribute the material 2101 through the passages 2105, 2112 after the device 2100 has advanced to the target position and / or after the applicator portion 2100 has advanced to a second or deployed state or position (shown in FIG. 48).

[0236] Device 2100 can optionally be configured such that applicator 2106 can be selectively connected to inner sleeve 2104 at connection portion 2122. In this configuration, device 2100 can enable a plurality of additional functions that would not be possible without connectable interface 2122. As a first example, after a desired procedure has been formed in substance 2101 and applied to the target surface, the user of the device can remove applicator 2106 from inner sleeve 2104 with connector 2122, such that outer sleeve 2102 and inner sleeve 2104 can be withdrawn from the target position without pulling out applicator 2106 or a part thereof such as applicator portion 2110. For example, in some applications such as an ophthalmic application, it may be desirable to keep applicator 2106 in contact with the eye tissue until a desired level of healing is achieved or indefinitely. Thereafter, distal tip 2106 or a part thereof can remain in the target position or be removed from the target position by any suitable means including reconnecting applicator 2106 to inner sleeve 2104 and retracting applicator 2106 into outer sleeve 2102. Distal tip 2106 can be made from a bioabsorbable material, an inert material, etc. If inert and remaining in the target position, applicator portion 2110 can provide additional scaffolding or support to the tissue even after the substance has dissolved or dissipated.

[0237] In any embodiment, the device 2100, including but not limited to the passage 2105 of the inner sleeve 2104, can be pre-filled with the substance 2101 and stored in this partially filled state. The applicator 2106 can be provided in an unattached or detached state where the applicator 2106 is detached from the inner sleeve 2104 and contains no substance 2101. In this configuration, after the applicator 2106 is coupled to the inner sleeve 2104 by the connector 2122, the user can advance the substance 2101 through the passage 2112 of the elongated portion 2108 of the application tip 2106 and through the opening 2114 onto the applicator portion 2110 when the applicator portion 2110 is in either the first state or the second state.

[0238] The connector 2122 in any embodiment disclosed herein can be configured to self-seal such that when the applicator 2106 is separated from the inner sleeve 2104, the connector 2122 seals the passage 2105 of the inner sleeve 2104 to prevent the discharge of any substance within the passage number 2105 of the inner sleeve 2104 through the connector 2122.

[0239] Any embodiment of the applicator portion 2110 can be optionally configured to be less flexible in the longitudinal direction (shown as L in FIG. 49) than in the width direction W. The material of the applicator portion 2110 can be configured to have reinforcing features or materials such as, but not limited to, folds, reinforcing wires, wire loops, ribs, sheets, or other structural members made from other features such as nitinol, stainless steel, or other alloys, channels, ribs, or features such as the longitudinal direction, to increase the longitudinal rigidity of the applicator portion 2110 and decrease the widthwise rigidity of the applicator portion 2110.

[0240] Furthermore, some embodiments can optionally be configured to dispense or apply a flexible film of a substance to a surface or to deliver any substance or material through a small opening of the eye into a sealed space such as the eye.

[0241] FIG. 53 shows a top view of another embodiment of an applicator tip 2156 that can be used with any of the embodiments of the devices disclosed herein, including but not limited to any of the devices 2100 disclosed above. The applicator tip 2156 can include any of the features, materials, or other details of any of the other embodiments of the applicator tips disclosed herein, and in combination with or instead of any of the features described below, including but not limited to the applicator 2106 described above, to form new embodiments.

[0242] Referring to FIG. 53, the applicator portion 2160 can include a plurality of openings 2163 in fluid communication with a passageway 2162 that extends through the elongate portion 2158. The plurality of openings 2163 can be formed in any desired pattern and in any desired number around a first surface 2160a of the applicator portion 2160. For example, but not limited to, the applicator portion 2160 can have about 20 openings 2163 formed therein, or 5 or about 5 to 40 or about 40 openings formed therein, or 10 or about 10 to 30 or about 30 openings formed therein, or 15 or about 15 to 25 or about 25 openings formed therein, or any number of openings 2163 within these ranges, or any range of numbers of openings 2163 within these ranges.

[0243] The opening 2163 can provide or enable a more uniform distribution of the substance 2101 across the first surface 2160a of the applicator portion 2160. Further, since the opening 2163 extends only through the first surface 2160a of the applicator portion 2160 to the passage 2162, the flexibility and / or crushability of the applicator portion 2160 can be enhanced, such that the applicator portion 2160 facilitates the crushing, bending, and / or retraction of the applicator portion 2160 within the outer sleeve of the device when the device is in the first or retracted state.

[0244] FIG. 54A is a cross-sectional view of another embodiment of a device 2200 for applying a substance 2101 to a surface of an object, showing the device 2200 in a second or deployed state. The device 2200 can include any features, materials, or other details of any of the other device embodiments disclosed herein, including, but not limited to, the device 2100 described above, in combination with or instead of any of the features described below.

[0245] In some embodiments, the device 2200 can include a cannula or outer sleeve 2202 (also referred to herein as an elongated body) having an internal conduit or passage 2203 through which the substance 2101 can be advanced, and an applicator tip 2206 coupled to an inner core 2204. The applicator tip 2206 and the inner core 2204 can be movable (e.g., telescopic) within the outer sleeve 2202. In some embodiments, the applicator tip 2206 and the inner core 2204 can be rotatable within the outer sleeve 2202. The outer sleeve 2202 can be configured to facilitate or improve user control of the device 2200 during application of the substance 2101 and to provide additional rigidity and operability to the applicator tip 2206 for advancing the substance to an applicator portion 2210 of the applicator tip 2206 via the device 2200.

[0246] The distal end portion 2206a of the applicator tip 2206 can extend from the distal end 2202a of the cannula or outer sleeve 2202. In any embodiment, the applicator tip 2206 can have an elongated portion 2208 and an applicator portion 2210. The seal 2222 can optionally be disposed at the distal end 2202a of the outer sleeve 2202 of the device 2200 to seal around the outer surface of the elongated body 2208, except for a channel or passage that is aligned with the first surface 2210a of the applicator portion 2210 (which can be referred to as the applicator surface). Further, similar to any of the embodiments disclosed herein, a fluoroscopic or radiopaque marker can be disposed along the outer sheath 2202, such as at the distal end 2202a of the outer sheath 2202, and / or along the applicator tip 2206 to provide visualization of the position of these components to the surgeon.

[0247] In this embodiment, as shown in FIG. 54A, since the substance 2101 can communicate through the space inside the outer sleeve 2202 between the outer surface of the elongated body 2208 and the inner surface of the outer sleeve 2202, there is no need to form a separate conduit through the elongated body 2208 and the applicator tip 2206. In some embodiments, a channel or space can be formed along the length of the outer surface of the inner core 2204 or the inner surface of the outer sleeve 2202, and the substance 2101 can be advanced along or through it. In other embodiments, as shown in FIG. 54B, the outer sleeve 2202 can have a separate conduit 2203 through which the substance 2101 can be advanced.

[0248] In some embodiments, the elongated body 2208 can extend from at least the proximal end of the outer sleeve 2202 to the applicator portion 2210 such that a separate inner core is not required. In some embodiments, the proximal end of the elongated body 2208 or the inner core 2204 can extend beyond or through the handle (optionally, with a suitable seal as needed) so that a user can operate the elongated body 2208 to advance and retract the applicator portion 2210 as needed. Similar to the applicator portion 2110 described above, the applicator portion 2210 can be configured to be retractable within the outer sleeve 2202 and configured to be movable between a first or closed state and a second or extended state. For example, but not limited to, the applicator tip 2206 is retracted within the outer sleeve 2202 and then extended when the substance 2101 advances beyond the distal end 2202a of the outer sleeve 2202, such that when the distal portion 2206a of the applicator tip 2206 advances distally relative to the distal end 2202a of the outer sleeve 2202, the substance 2101 can be applied along the length of the applicator tip 2206 to the distal portion 2206a of the applicator tip 2206.

[0249] In any embodiment of the device 2200, the handle, cannula or outer sheath 2202, inner sheath 2204, or other rigid or semi-rigid component can be made of or include any suitable plastic material, metal, polyvinyl chloride, glass, acrylic, carbon fiber, and / or any combination of the foregoing. In some embodiments, the cannula tip plug or protective tip cover can include plastic, metal, polyvinyl chloride, glass, acrylic, carbon fiber, rubber (e.g., but not limited to, silicone), and / or any combination of the foregoing.

[0250] Any embodiment disclosed herein can have a handle (not shown) at the proximal end of device 2100. The handle can have any details of any current or existing design of a biomaterial or other liquid material delivery device. In some embodiments, the handle can have a first handle portion or member that can couple to the outer sleeve 2102 of device 2100. An additional or second handle can be coupled to the inner sleeve 2104. The second handle member can be movably independent of the first handle member such that a user can advance and retract the inner sleeve 2104, and thus the applicator 2106 if coupled to the inner sleeve 2104, relative to the outer sleeve 2102.

[0251] A dispensing device or means (not shown) for dispensing substance 2101 into passageway 2105 can be in fluid communication with the proximal end 2104b of inner sleeve 2104. The dispensing device can be coupled to or otherwise be part of the handle of device 2100. In some embodiments, the dispensing device can include a plunger or syringe, a fillable chamber capable of holding or containing the substance, a compressible valve, a compressible bladder, or other devices configured to expel substance 2101 through passageway 2105. Additional mechanisms for advancing substance 2101 into inner sleeve 2104 can include a mechanical pump, a power pump, a pneumatic pump or cylinder, electromechanical pumping means, and the like. Optionally, the handle can include a port configured to receive an adhesive material therein. A bladder or other ejector device of a material as described herein can be coupled in fluid communication with the port.

[0252] Figure 55A shows an example of a system and / or device that includes a plunger 241, a handle 235, a cavity 240 for holding a bioadhesive material, an extender knob 236, a rod 238, a lock connector 239, and a flexible loop 237 that includes a film 237 of the bioadhesive material (partially extended). The plunger 241 may be used to expel the bioadhesive material through a hollow cannula and / or into the flexible loop 237 when pressed by a user (e.g., using pressure from the user's finger or pneumatic pressure supplied by an external device connected to the handle). In some embodiments, the plunger 241 is incorporated into the examples of FIGS. 55B and / or 55C. For example, the extender knob 236 can be used to extend the flexible loop 237 from a retracted position as shown in FIG. 55B. In some embodiments, the flexible loop 237 can be replaced with any of the applicator tips disclosed elsewhere in this specification.

[0253] Figure 55B shows an example of a system and / or device that includes an extender knob 236, a rod 238, a flexible loop that includes a film 237 of the bioadhesive material, and two guide ridges 242. Some embodiments include a retractable loop such as that of FIG. 55B that extends as shown in FIGS. 55A and / or 55C.

[0254] Figure 55C shows an example of a system and / or device that includes a handle 247, a rod 238, a cannula 248, and a flexible loop that includes a film 237 of the bioadhesive material. The cannula may be removable or non-removable.

[0255] Any component of device 2100 in any of the embodiments disclosed herein, including but not limited to the handle portion, outer sleeve 2102, inner sleeve 2104, and / or distal tip 2106, can be configured to have a temperature regulation function. In some embodiments, the outer sleeve 2102, inner sleeve 2104, and / or distal tip 2106 can optionally be configured to release heat from the device that can result from any heat generated by the substance 2101 as the substance 2101 advances through the device 2100. For example, one or more of the outer sleeve 2102, inner sleeve 2104, and distal tip 2106 can optionally be made of a material such as a thermally conductive metal (e.g., copper, steel, nitinol, aluminum, or other alloys, etc.) that has improved or enhanced thermal conductivity capable of conducting heat from a particular portion of the device 2100, or can include other materials. In some embodiments, the outer sleeve 2102 and / or inner sleeve 2104 can optionally be configured to conduct or release heat, while the applicator 2106 is not configured to release or conduct heat.

[0256] Alternatively, the outer sleeve 2102, inner sleeve 2104, and / or distal tip 2106 can optionally be configured to retain heat within one or more components of the device that can result from any heat generated by the substance 2101 as the substance 2101 advances through the device 2100. For example, one or more of the outer sleeve 2102, inner sleeve 2104, and distal tip 2106 can optionally be made of a material that has improved or enhanced heat insulation capabilities capable of reducing the amount of heat conducted from a particular portion of the device 2100. In some embodiments, the outer sleeve 2102 and / or inner sleeve 2104 can optionally be configured to retain heat, while the applicator 2106 is not configured to retain heat.

[0257] In some embodiments, one or more of the components of device 2100 (which can include outer sleeve 2102 and inner sleeve 2104, or optionally outer sleeve 2102, inner sleeve 2104, and applicator 2106) can be pre-cooled to a desired temperature lower than room temperature or body temperature so that the temperature of device 2100 does not rise above a desired temperature threshold if any heat is generated by substance 2101, and the desired temperature threshold can optionally be the patient's body temperature.

[0258] Furthermore, in some embodiments, one or more of the components of device 2100 (which can include outer sleeve 2102 and inner sleeve 2104, or optionally, outer sleeve 2102, inner sleeve 2104, and applicator 2106) can be configured to maintain a substance 2101 (which can be a hydrogel) at a temperature below a threshold temperature value such that the adhesive properties or ability of the substance decreases when the substance is contained within the device. Advancing the substance 2101 onto the applicator portion 2110 or applying the substance 2101 onto a target tissue or surface can increase the temperature of the substance and thus its adhesive properties. For example, without limitation, the outer sleeve 2102 can be sized and configured such that the inner diameter of passage 2103 is larger than the outer surface of the inner sleeve 2104 so as to form a space between the inner surface of the outer sleeve 2102 and the outer surface of the inner sleeve 2104. A cooling fluid can be directed through individual conduits or otherwise through passage 2103 to provide a cooling source to the inner sleeve 2104 and thus to the substance 2101. One or more seals can be used to seal the end of the outer sleeve 2102 to the inner sleeve 2104 so that the cooling fluid does not leak from the device 2101. Alternatively, an outer shell configured to surround the outer sleeve 2102 can be disposed around the entire outer sleeve 2102 to provide additional cavities or passages for the communication of a cooling fluid within the outer sleeve 2102 and thus to lower the temperature of the substance 2101. The inlet port and the outlet port can be formed within or coupled to a handle for the inlet and outlet of the cooling fluid through the device 2100. The cooling fluid can optionally include ammonium nitrate.

[0259] Optionally, a rheostat and / or other means can be placed within the handle and used to control the temperature of any or all of the components of device 2100. Optionally, one or more thermal sensors or other sensors can be used to monitor the temperature of any or all of the components of device 2100. Further, any embodiment of device 2100 disclosed herein can be configured to automatically maintain the temperature of a portion of the device within a specified range even if a substance or application tends to raise the temperature of the device or its components.

[0260] Further, any embodiment of device 2100 disclosed herein can be configured to transfer heat to one or more of the components of device 2100 (which can include only the outer sleeve 2102 and inner sleeve 2104, or optionally the outer sleeve 2102, inner sleeve 2104, and applicator 2106, or optionally only the applicator 2106 or applicator portion 2110) to raise the temperature of the substance 2101 contained within the device and / or applicator tip and transfer or deliver heat to the target tissue. In some embodiments, without limitation, a thermally conductive material such as copper, steel, nitinol, aluminum, or other alloys can be integrated into the device and extended longitudinally along the device to transfer heat from a heat source adjacent to the proximal end or handle of the device to the applicator 2106. Optionally, one or more thermoelectric components or means can be used to transfer heat to one or more of the components of device 2100 (which can include only the outer sleeve 2102 and inner sleeve 2104, or optionally the outer sleeve 2102, inner sleeve 2104, and applicator 2106, or optionally only the applicator 2106 or applicator portion 2110).

[0261] In any of the embodiments disclosed herein, the device or method can include raising or lowering the temperature of the inner sleeve 2104, the applicator 2106, or the applicator portion 2110, as needed, in response to certain thermal response characteristics of the material, to remove or liquefy a solidified substance or gel from the device 2100 or the tissue surface (such as tissue on the surface of the eye). The liquefied substance or gel can then be aspirated through the device and removed through the proximal end of the device or the handle portion. The device can optionally be configured to have one or more suction tubes or suction channels for aspirating any liquefied substance or gel, or any other substance that it is desirable to remove from the device. The tubes can optionally be heated or temperature controlled to ensure that the removed substance remains in a liquid state.

[0262] Any of the embodiments of the devices disclosed herein can include an internal ablation component. Such embodiments can include a cannula having a fiber or wire for light or ablation. FIG. 56 shows an example of a cannula having a fiber or wire for light or ablation. This example includes an optical fiber 265 within a tube along the edge of the cannula. The optical fiber 265 includes an angled end 262 in this example, although in some embodiments, the end of the optical fiber 265 is straight. The end 262 of the optical fiber 265 can be angled at an angle that matches the angle of the slope of the cannula tip if it is angled. This example includes illumination 260 emitted by the end 262 of the optical fiber 265.

[0263] In some embodiments, the cannula tip can be configured for use in cauterization. For example, it can include an additional tube configured for the passage of additional materials (such as liquids) that can be expressed as a spray or droplets from the cannula tip. For example, the additional materials may be used to activate a bioadhesive material. In some embodiments, the device or system, or its components such as the handle, cannula, cannula tip, light, or optical fiber, can be configured to emit light at a wavelength that activates, thickens, or cures the bioadhesive material.

[0264] The system and / or device can be operated to raise the temperature of the cannula tip (e.g., using an internal cauterization component). This is advantageous, according to some embodiments, in assisting the release of the bioadhesive from the applicator portion when the bioadhesive material is a temperature-responsive material that is more fluid at higher temperatures. Some embodiments include cryotherapy components such as a cryotherapy handpiece. In some embodiments, the system or device can be operated to lower the temperature of the applicator tip (e.g., using a cryotherapy component). This is advantageous, according to some embodiments, in assisting the release of the bioadhesion from the applicator portion when the bioadhesive material is a temperature-responsive material that is more fluid, fragile, or releasable at lower temperatures.

[0265] The substances used in conjunction with any of the embodiments disclosed herein can include thermally active substances. Further, the device can optionally be configured to provide a source of warm or cool air onto the substance through additional tubing inside the inner cannula 2104, through additional tubing or passageways outside the inner cannula 2104, through a completely separate cannula from a separate device, or in other ways. The warm or cool air can be directed onto the substance to which it is applied. The device can optionally include a filter for filtering the air before heating or cooling the air and applying it to the substance. In any embodiment, the air source passageway can have any of the sizes disclosed herein for the outer cannula 2102 and / or the inner cannula 2104. The source of warm or cool air can be a self - standing piece of equipment, can be incorporated into the outer or inner cannula, or can be incorporated into other surgical devices such as a vitrectomy machine configured to filter air and send it to the eye or other instrument.

[0266] Any embodiment of the devices disclosed herein can be incorporated into or included in a kit or system that also includes one or more substances (which can be any of the substances disclosed herein or other substances currently known or later developed). The kit can also include a material dispenser for dispensing the substance if not already included in the device. The kit can also optionally include a tip plug or protective cover for the distal end of the device if not already included in the device. The system, device, or kit can be sterilized or pre - sterilized. In some embodiments, the kit includes the pre - sterilized material dispenser described herein.

[0267] The kit or system can also include any of the other components or devices disclosed herein, such as, but not limited to, one or more of a curing component and a device for applying the curing component to the substance after the substance has been applied to the target tissue surface. Further, in any of the embodiments disclosed herein, the substance or one or more different substances may be provided within an opening, port, or capsule or self - contained syringe that can be coupled in other ways of the handle portion of the device.

[0268] Some embodiments relate to the use of a system, device or kit for applying a substance (which can include any of the substances listed above, including a bioadhesive) to the eye or retina for the repair of the eye, such as including the retina, sclera, conjunctiva, and cornea. In any such method, the cannula can optionally be advanced into the eye using any known or commonly used technique. The surgical procedures disclosed herein can include piercing the surface of the eye or other tissues of the eye, or can include treating the eye tissue without entering or piercing the eye tissue.

[0269] The methods disclosed herein can include advancing a substance to an applicator portion at the tip of the applicator and from the applicator portion to the eye tissue or a target tissue that can optionally be retinal tissue. Any of the embodiments disclosed herein can optionally be used to repair retinal tears or other defects or tissues in the body, as disclosed elsewhere herein and in other surgical applications beyond those disclosed herein. Some embodiments include, for example, the operation of buttons on the handpiece of a device or system, other manual controls, or the operation of a foot pedal to control a valve for controlling the aspiration of a substance, the injection of a substance, the injection or delivery of an activating solution or other curing means, allowing the substance to flow through passages of the handpiece and / or passages of the device.

[0270] Any embodiment disclosed herein can include means for curing a substance after it has been applied to a target surface, including, but not limited to, light-emitting devices, UV radiation devices, high-temperature applications (e.g., applying heat), low-temperature applications (e.g., applying cooling).

[0271] Any embodiment disclosed herein can also be configured for application outside of the eye tissue, including, but not limited to, applications in gastrointestinal tissue, colon tissue, etc.

[0272] In some embodiments, the material delivered by the device can be delivered trans-corneally. For trans-corneal use, delivery via the device can use a cutting action to remove the cohesive / adhesive material after delivery. In some embodiments, the excess can be removed by a vitreous cutter and / or aspiration. Trans-corneal delivery can be utilized in an air-filled eye to avoid adhesive material floating on non-target eye structures such as the lens / IOL / ciliary body portion / corneal angle, corneal endothelium, etc., which can cause obstruction of the view through the lens / IOL or impairment of the inflow / outflow of aqueous humor.

[0273] During application of the substance, one or more portions of the tissue can be covered with a fluid to protect such tissue or mask such tissue to avoid contact with the substance. Additionally, air can be used to control the application of the substance and / or avoid contact of the substance with some tissue surfaces. For example, but not limited to, an air disk can be created to cover or protect the tissue surface, the adhesive material can settle on the fluid surface rather than on the underlying structure, and / or can be immediately activated (made non-adhesive) to avoid adhesion to non-target tissue. Activation in any embodiment disclosed herein can include activation by water or a similar liquid. If the substance is heat-reactive, any unwanted material can have its temperature regulated by any embodiment of this device so that the material can be converted to a liquid form and then aspirated from the eye.

[0274] Scleral delivery is contemplated and may include delivery of a material to a retinal break through the subretinal space. After the material is delivered via the tapered end of a device or needle and adheres to the retina, the material may be severed when the needle is withdrawn from the sclera. The material may act as a buffer to prevent fitting of the retina into the scleral defect by a cannula, needle, or device utilized to cross the scleral tissue and choroid tissue.

[0275] The delivery device may be single, double, or triple bore. In some embodiments, a double bore device includes one bore for delivering a material and a second bore for refluxing intraocular fluid out of the eye as the TOP increases. In some embodiments, one of the bores includes an optical fiber that can be used for illumination. In some embodiments, one of the bores includes a fiber for delivering laser light. In some embodiments, one of the bores includes a fiber for delivering heat or some other energy source used to cure the injected material.

[0276] In some embodiments, a triple bore device includes one bore for delivering a material, one bore for passing a gas used to create a bubble or film of an adhesive material, and a third bore for refluxing intraocular fluid out of the eye as the IOP increases.

[0277] Figures 59-64 illustrate an optional method of using an embodiment of device 2300. Referring to Figure 59, cannula 2302 can be advanced into the eye. As shown in Figure 59, as the cannula advances into the eye, applicator portion 2310 can be placed within cannula 2302 or drawn into cannula 2302. In some embodiments, applicator portion 2310 can have a substance on applicator portion 2310 when the applicator portion is placed within cannula 2302. In some embodiments, as described below, a substance can be applied to applicator portion 2310 after applicator portion 2310 has advanced distally beyond the distal end of cannula 2302. Thereafter, as shown in Figure 60, applicator portion 2310 can extend from the distal end of cannula 2302 and expand to a second or expanded state. Cannula 2338 (also referred to herein as a supply cannula) can extend through outer cannula 2302. Figure 61 shows cannula 2302 extending such that the distal end of cannula 2338 is substantially aligned with the distal end of outer cannula 2338. Cannula 2338 can extend beyond the distal end of outer cannula 2302 and toward distal end 2310a of applicator portion 2310 of the applicator tip, as shown in Figure 62. Thereafter, as shown in Figure 63, substance 2101 can be advanced through passageway 2340 of cannula 2338 and released onto applicator portion 2101. Thereafter, as shown in Figure 64, the user can move and manipulate outer cannula 2302 and applicator portion 2310 to apply substance 2101 to the target tissue.

[0278] Some embodiments of the system and / or device further include an internal material supply chamber within the handpiece or cannula for cooling or heating a fluid, or other fluid or gas that can be used with device 2100. The internal material supply chamber can optionally include an elongated body including a proximal end and a distal end including a material supply tip and / or an outlet port. The internal material supply chamber can optionally be at least partially within or adjacent to at least a portion of passageway 2105.

[0279] In some embodiments of the system and / or device, the internal material supply chamber, the elongated body of the internal material supply chamber, the material supply tip, and / or the material supply outlet port include a cross-sectional diameter of 0.1 - 0.5 mm, 0.5 - 1 mm, 1 - 2 mm, 2 - 3 mm, 3 - 4 mm, 4 - 5 mm, 5 - 6 mm, 6 - 7 mm, 7 - 8 mm, 8 - 9 mm, 9 - 10 mm, 10 - 20 mm, 20 - 30 mm, 30 - 40 mm, or 40 - 50 mm. In some embodiments of the system or device, the internal material supply chamber, the elongated body of the internal material supply chamber, the material supply tip, and / or the material supply outlet port include a length of 0.1 - 0.5 mm, 0.5 - 1 mm, 1 - 2 mm, 2 - 3 mm, 3 - 4 mm, 4 - 5 mm, 5 - 6 mm, 6 - 7 mm, 7 - 8 mm, 8 - 9 mm, 9 - 10 mm, 10 - 20 mm, 20 - 30 mm, 30 - 40 mm, 40 - 50 mm, 50 - 60 mm, 60 - 70 mm, 70 - 80 mm, 80 - 90 mm, 90 - 100 mm, 100 - 150 mm, or 150 - 200 mm.

[0280] Some embodiments of the system and / or device further include a second internal material supply chamber. In some embodiments of the system or device, the internal material supply chamber and the second internal material supply chamber each include a separate bioadhesive material, such as a polyethylene glycol solution and a triethylamine solution, a hydrogel, a bilayer hydrogel, or a polymeric hydrogel.

[0281] FIG. 65A is a perspective view of an end of an embodiment of a cannula 2402 that can be used with any embodiment of the devices disclosed herein. FIG. 65B is a cross-sectional view of the embodiment of the cannula 2402 shown in FIG. 65A taken along line 65B-65B of FIG. 65A. FIG. 65C is a top view of the embodiment of the cannula 2402 shown in FIG. 65A. As shown, the cannula 2402 can have a notch or cutout 2404 formed at an end of the cannula 2402, which can assist in the retraction or size reduction (e.g., constriction or crushing) of any of the embodiments of the applicator portion disclosed herein when the applicator portion is drawn into the outer sleeve or distal end of the cannula. Referring to FIG. 65C, in some embodiments, the cutout 2404 can have an asymmetric shape about a plane that passes through the axial centerline C of the cannula 2402 and, for example, without limitation, passes through the axial centerline C and through a plane perpendicular to the plane of the figure (e.g., perpendicular to the plane of the paper). In some embodiments, the notch 2404 can terminate in a curved end 2406. In other embodiments, the notch 2404 can have a triangular shape where one side of the notch is parallel to the axial centerline of the cannula. In other embodiments, the notch can have a triangular shape where both sides of the notch are tapered or angled or otherwise “v”-shaped, such as the notch 2424 of the cannula 2422 shown in FIGS. 67A and 67B. In some embodiments, as shown in FIG. 67B, the apex or proximal end portion 2424a of the v-shaped notch can be rounded or have a radius. In other embodiments, the notch can have a rounded end and parallel sides, as in FIG. 67C, or otherwise can have a generally “u” shape.

[0282] Furthermore, referring to FIG. 65C, the notch (including but not limited to notches 2404, 2414, and 2424) of any embodiment disclosed herein can have a length L and a width W adjacent to the end of the cannula 2402, and the embodiments of the cannula disclosed herein can have a diameter D. For example, but not limited to, the width W of the notch (or the width W1 of notch 2414) can be 30% (or about 30%) of the diameter D of the cannula, or 20% (or about 20% or less than 20%) to 100% (or about 100% or more than 100%) of the diameter D of the cannula, or 30% (or about 30%) to 50% (or about 50%) of the diameter D of the cannula, or any value from any value within these ranges. In some embodiments, the width W of the notch (or the width W1 of notch 2414) can be from 0.25 mm (or about 0.25 mm), or 0.1 mm (or, in some embodiments, about 0.1 mm or less than 0.1 mm) to 1.5 mm (or, in some embodiments, about 1.5 mm or more than 1.5 mm), or from 0.25 mm (or, in some embodiments, about 0.25 mm) to 0.75 mm (or, in some embodiments, about 0.75 mm), or any value from any value within these ranges.

[0283] In any embodiment, the length L of the notch of any embodiment disclosed herein can be about 30% of the length of the applicator portion, or from 20% (or about 20% or less than 20%) to 100% (or about 100% or more than 100%) of the length of the applicator portion, or from 30% (or about 30%) to 60% (or about 60%) of the length of the applicator portion, or from 30% (or about 30%) to 50% (or about 50%) of the length of the applicator portion, or from any value within these ranges to any value. In some embodiments, the length of the notch can be from about 1 mm, or 0.5 mm (or, in some embodiments, about 0.5 mm or less than 0.5 mm) to 2 mm (or, in some embodiments, about 2 mm or more than 2 mm), or from 0.75 mm (or, in some embodiments, about 0.75 mm) to 1 mm (or, in some embodiments, about 1 mm), or from any value within these ranges to any value.

[0284] Figures 66A and 66C are perspective and top views of an end of another embodiment of cannula 2412 that can be used with any embodiment of the devices disclosed herein. Figure 66B is a cross-sectional view of the embodiment of cannula 2412 shown in Figure 66A taken along line 66B-66B of Figure 66A. As shown, cannula 2412 can have a notch or cutout 2414 formed at the end of cannula 2412, which can assist in the deployment and / or retraction or crushing of any of the embodiments of the applicator portion disclosed herein. Referring to Figure 65C, in some embodiments, cutout 2414 can have an asymmetric shape about a plane that passes through the axial centerline C of cannula 2412, for example, but not limited to, a plane that passes through the axial centerline C and extends around a plane perpendicular to the plane of the figure (e.g., perpendicular to the plane of the paper).

[0285] Furthermore, in any embodiment, the notch 2414 can be a double notch having a first portion 2414a and a second portion 2414b that is narrower than the first portion 2414a. For example, without limitation, the first portion 2414a can have a width W1 that can be about twice the width W2 of the second portion 2414b, or can be from 50% greater (or about 50% greater) to 100% greater (or about 100% greater) than the width W2 of the second portion 414b. In any embodiment, the first portion 2414a of the notch 2414 can have a length L1 that is 50% (or about 50%) of the total length L of the notch 2414, or a length L1 that is from 30% (or about 30% or less than 30%) to 80% (or about 80% or less than 80%) of the total length L of the notch 2414, or a length L1 that is from 40% (or about 40%) to 60% (or about 60% or less than 60%) of the total length L of the notch 2414. In some embodiments, the notch 2414 can terminate at a curved end 2416.

[0286] FIG. 68 is a top view of another embodiment of a device 2450 having an applicator 2456 that can be used with any of the embodiments of the devices disclosed herein. The device 2450 and / or the applicator 2456 can include any of the components, features, materials, and / or other details of any of the embodiments of the other devices or applicators disclosed herein, and can be combined with, or alternatively include, without limitation, the device 2100 and / or the applicator 2106 described above, to form new embodiments in combination with any of the features described below. Referring to FIG. 68, the applicator 2456 can have an applicator portion 2460 coupled to a core member or elongated body 2454 that extends through at least a portion (or all) of the device 2450.

[0287] Referring to FIG. 72, which is a cross-sectional view of an embodiment of applicator portion 2460 that can be used with an embodiment of any device disclosed herein along line 72-72 of FIG. 68, the cross-sectional view is perpendicular to the axial centerline of applicator 2456. As shown, some embodiments of applicator portion 2460 can have a shape symmetric about a central plane C and can have a generally uniform thickness across the full width of applicator portion 2460.

[0288] FIG. 73 is a cross-sectional view of another embodiment of applicator portion 2470 that can be used with an embodiment of any device disclosed herein, and the cross-sectional view is perpendicular to the axial centerline of the applicator. As shown, some embodiments of applicator portion 2470 can have a shape symmetric about a central plane C and can have a tapered thickness, with applicator portion 2470 tapering from a first thickness T1 at the central portion of applicator portion 2470 to a second, thinner thickness T2 at one or both sides of applicator portion 2470. In some embodiments, as shown in FIG. 73, the bottom surface 2472 and / or top surface 2474 of applicator portion 2470 can be angled from the central portion of applicator portion 2470 towards the side edges of applicator portion 2470. In other embodiments, as shown in FIGS. 74 and 75, the bottom surface 2472 and / or top surface 2474 of applicator portion 2470 can be generally planar from the central portion of applicator portion 2470 towards the side edges of applicator portion 2470.

[0289] In any of the embodiments disclosed herein, the bottom surface and / or the top surface of the applicator portion may be concave or curved from the central portion of the applicator portion 2470 towards the side edges of the applicator portion 2470. For example, but not limited to, as shown in FIG. 74, the top surface 2484 of the applicator portion 2480 can be curved from the central portion of the applicator portion 2470 towards the side edges of the applicator portion. In any of the embodiments disclosed herein, the central portion having an increased thickness (such as thickness T1) may be narrow like the central portion 2486 of the embodiment of the applicator portion 2480 shown in FIG. 74, or may be wide like the central portion 2496 of the embodiment of the applicator portion 2490 shown in FIG. 75 or the central portion 2664 of the embodiment of the applicator portion 2650 shown in FIG. 71. For example, but not limited to, the central portion can have a width of 30% (or about 30%) of the width of the entire applicator portion, or from 10% (or about 10% or less than 10%) to 60% (or about 60% or more than 60%), or from 20% (or about 20%) to 40% (or about 40%) of the width of the entire applicator portion.

[0290] In some embodiments, the first thickness T1 can be 0.2 mm (or about 0.2 mm), or from 0.1 mm (or about 0.1 mm or less than 0.1 mm) to about 1 mm (or about 1 mm or more than 1 mm), or from 0.15 mm (or about 0.15 mm) to about 0.5 mm (or about 0.5 mm), or any value from any value within these ranges. In any embodiment, the second thickness T2 can be 0.1 mm (or about 0.1 mm), or from 0.05 mm (or about 0.05 mm or less than 0.05 mm) to about 0.5 mm (or about 0.5 mm or more than 0.5 mm), or from 0.075 mm (or about 0.075 mm) to about 0.25 mm (or about 0.25 mm), or any value from any value within these ranges.

[0291] In some embodiments, the first thickness T1 can be 50% (or about 50%), or from 10% (or about 10% or less than 10%) to about 80% (or about 80% or more than 80%), or from 20% (or about 20%) to about 60% (or about 60%), or from 30% (or about 30%) to about 40% (or about 40%), or any value to any value within these ranges.

[0292] Furthermore, in any of the embodiments disclosed herein, the applicator portion 2470 can have an asymmetric cross-section such that the first side of the applicator portion 2470 has a different shape and / or thickness compared to the shape and / or thickness of the second side 2470, and the first and second sides can be defined to be divided by a centerline axis C. For example, as shown in FIG. 76 which is a cross-sectional view of another embodiment of the applicator portion 2500 that can be used in any of the device embodiments disclosed herein, the first side 2502 can have a first shape and thickness profile that is different from the second shape and thickness profile of the second side 2504 of the applicator portion 2500. The thickness T1 of the central portion can be greater than the thickness T2 of the side edge or side of the first side 2502, and the thickness T3 of the side edge or side of the second side 2504 can be greater than the thickness T2 of the side edge or side of the first side 2502. Furthermore, in any of the embodiments disclosed herein, the shape of the bottom surface 2506 can be different from the shape of the top surface 2508, the shape of the bottom surface 2506 on the first side 2502 can be the same as or different from the shape of the bottom surface 2506 on the second side 2504, and / or the shape of the top surface 2508 on the first side 2502 can be the same as or different from the shape of the top surface 2508 on the second side 2504.

[0293] FIG. 69 is a top view of another embodiment of a device 2550 having an applicator 2552 that can be used with any device embodiment disclosed herein. Device 2550 and / or applicator 2556 can include any of the components, features, materials, and / or other details of any of the other device or applicator embodiments disclosed herein, and can be combined with or alternatively include, without limitation, devices 2100, 2450 and / or applicators 2106, 2456 described above to form new embodiments in combination with any of the features described below. Referring to FIG. 69, applicator 2552 can have an applicator portion 2560 coupled to a core member or elongated body 2554 that extends through at least a portion (or all) of device 2550. Referring to FIG. 69, applicator portion 2560 can have a first tapered transition 2562 and a second tapered transition 2564. The first and second tapered transitions can assist in crushing, folding, rounding, bending, or shrinking the applicator portion when the applicator portion is drawn into the cannula. In some embodiments, the first and second tapered transitions 2562, 2564 can be symmetric about a centerline C of the applicator portion 2460. In other embodiments, the applicator portion can have tapered transitions on both sides of the applicator portion, but of different sizes and / or shapes, such as the first and second tapered transitions 2656, 2658 of the applicator portion 2650 of the embodiment shown in FIG. 71. For example, without limitation, the first tapered transition can be longer than the second tapered transition. In other embodiments, the applicator portion can have only one tapered transition, such as the applicator portion 2610 of the embodiment of device 2600 shown in FIG. 70.

[0294] Referring to FIG. 71, in any embodiment, the applicator portion (such as applicator portion 2650) can be configured such that the length L1 of the first sidewall portion (such as sidewall portion 2652, also referred to herein as the first side) is shorter than the total length L of the applicator portion due to the presence of the first tapered transition portion (such as first tapered transition portion 2656). For example, the length L1 of the first sidewall portion can be about 40% of the total length L of the applicator portion, or 30% or about 30% - about 50% of the total length of the applicator portion.

[0295] Furthermore, the length L2 of the second sidewall (such as sidewall portion 2654, also referred to herein as the second side) can be shorter than the length L1 of the first sidewall. This can be due to different lengths, angles, and / or other shapes of the second tapered sidewall portion (such as second tapered sidewall portion 2658), and / or a larger radius at the intersection of the second wall portion and the second tapered sidewall portion. The radius at the intersection of the second wall portion and the second tapered sidewall portion (such as radius R2 in FIG. 71) can be significantly larger than the radius at the intersection of the first wall portion and the first tapered sidewall portion (such as radius R1 in FIG. 71) (for example, 2 to 20 times or more, or 5 to 10 times or more, or any value or range of values within the aforementioned ranges). In any embodiment, the second side transition portion 2658 can be more gradual than the first side transition portion 2656 to facilitate crushing or shrinking of the applicator portion.

[0296] In some embodiments, the first side portion 2652 can have a first transition portion having a first length in the axial direction, and the second side portion 2654 can have a second transition portion having a second length in the axial direction that is greater than the first length of the first transition portion. In some embodiments, the shorter the length of the first transition portion, the more likely the first side portion 2652 of the applicator tip 2650 is to crush when the applicator portion 2650 is drawn into the outer sleeve of the device before the second side portion 2654 of the applicator portion 2650 crushes. Thereby, in some embodiments, the applicator portion 2650 can be crushed to a more compact size compared to a symmetric applicator portion.

[0297] FIG. 77 is a perspective view of an end of another embodiment of the delivery device 2700, showing an applicator 2702 coupled to an inner cannula 2704 in a retracted and crushed state within an outer cannula body or sleeve 2706 and a substance delivery cannula 2710 in a retracted state within the outer cannula body 2706. FIG. 78 is a perspective view of an end of the embodiment of the delivery device 2700 shown in FIG. 77, showing that the applicator 2702 is in a partially advanced position and in an expanded state. FIG. 78 also shows that in some embodiments, the delivery cannula 2710 can be axially extended such that it extends to the distal end portion of the applicator portion 2702 and can be drawn in while a substance is exuding from the substance delivery cannula 2710. The device 2700 can be configured to limit the extent of extension of the substance delivery cannula 2710 such that the substance delivery cannula does not extend beyond the distal end of the applicator portion 2702. The device 2700 can also be configured such that the substance delivery cannula 2710 is in a fixed position at or near the end of the sleeve 2706 and enables delivery of the substance onto the surface of the applicator 2702 when the applicator 2702 advances beyond the end of the outer cannula or sleeve 2706. In some embodiments, the only movable or extendable component of the device or the distal end portion of the device can be the applicator and the applicator portion that can be integrally connected.

[0298] Retinal breaks, i.e., discontinuities, defects, holes, and tears, exist in various shapes and sizes. Referring to FIG. 79, the breaks can exist, for example, as a crescent 3002, an oval 3004, or a circle 3006. The breaks can range in size from about 1 mm or less to more than half the area of the retina 3003. For example, the rectangular break 3005 occupies about 1 / 3 of the area of the retina 3003.

[0299] As shown in FIG. 80A, in order to adhere the retina to adjacent exposed cells, a bioadhesive 3008 can be applied to the boundary 3010 of the defect / retina junction of a circular retinal defect 3012 (or other shaped defect). As a result, the bioadhesive 3008 overlaps the edges 3010a, 3010b of the boundary 3010 that overlap the intact retinal tissue 3014 at the edge 3010a adjacent to the boundary 3010, and a part of the tissue 3016 remaining within the base of the retinal defect 3012, for example, covers the tissue 3016 at the edge 3010b adjacent to the boundary 3010, but not all. This remaining tissue 3016 left by the retinal defect can be any number of layers of retinal tissue including, but not limited to, retinal pigment epithelium (RPE), and may not have a layer of retinal tissue that leaves only bare scleral tissue (white outer eye wall), or may be a combination of retinal tissue and scleral tissue.

[0300] Alternatively, as shown in FIG. 80B, the bioadhesive 3008 can be applied to cover the entire retinal defect 3012 including the entire tissue 3016 within the defect and overlap the intact retinal tissue 3014 at the edge 3010a adjacent to the boundary 3010. The bioadhesive can be applied to the entire retinal tissue within the defect, the entire inner surface of the bare intact scleral tissue, or the entire combination of the retinal tissue and the bare intact scleral tissue within the defect.

[0301] Covering the entire defect 3012 is designed to reduce the likelihood that cells from within the retinal defect will move from their normal anatomical positions to different positions within the vitreous cavity or to other retina and eye tissues within the eye. Maintaining RPE cells in their normal monolayer configuration with normal cell polarity prevents or reduces the detachment of RPE cells from the base of the retinal defect, thereby reducing the likelihood of the onset of epithelial-mesenchymal transition and subsequent proliferative vitreoretinopathy. In the retina, during the process of epithelial-mesenchymal transition, RPE cells can differentiate into fibroblasts and myofibroblasts, and the fibroblasts and myofibroblasts can migrate and proliferate to form a contractile epiretinal membrane that damages eye tissues.

[0302] Furthermore, applying a bioadhesive to cover the entire retinal defect 3012 is designed to reduce the risk of low osmotic pressure, i.e., low intraocular pressure, by restricting the movement of body fluids across the RPE. Normal intraocular pressure is achieved by the balance between the inflow of aqueous humor produced by the ciliary body and the outflow through the trabecular meshwork, as well as by the combination of active and passive flows across the retinal pigment epithelium to the choroid that use choroidal osmotic pressure to draw fluid into the choroidal vascular system. An intact retina provides a significant resistance to this pathway of fluid flow across the RPE. When the area of the retinal tear is large, there is a possibility of substantial fluid movement across the RPE, which can lead to low intraocular pressure and related pathological changes (such as corneal folds, corneal edema, choroidal folds, and choroidal detachment).

[0303] In the methods shown in both FIGS. 80a and 80b, what is applied to the retinal tissue is preferably only the bioadhesive. That is, the methods of FIGS. 80a and 80b preferably do not include the application of a patch to the retinal tissue and are thus "patchless" techniques.

[0304] While specific embodiments of the present invention have been described, these embodiments are presented by way of example and are not intended to limit the scope of the present disclosure. In fact, the novel methods and systems described herein can be embodied in various other forms. Also, various omissions, substitutions, and changes can be made to the systems and methods without departing from the gist of the present disclosure. The appended claims and their equivalents are intended to cover such forms or modifications as fall within the scope and spirit of the present disclosure. Accordingly, the scope of the present invention is defined only by reference to the appended claims.

[0305] Features, materials, characteristics, or groups described in connection with a particular aspect, embodiment, or example are to be understood as applicable to any other aspect, embodiment, or example described in this section or elsewhere in this specification, unless incompatible therewith. All features disclosed in this specification (including the appended claims, abstract, and drawings), and / or all steps of any method or process so disclosed, can be combined in any combination, except combinations where at least some of such features and / or steps are mutually exclusive. Protection is not limited to the details of any of the foregoing embodiments. Protection extends to any novel one, or any novel combination, of the features disclosed in this specification (including the appended claims, abstract, and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed.

[0306] Furthermore, the specific features described in this disclosure in the context of separate implementations can also be implemented in combination in a single embodiment. Conversely, the various features described in the context of a single implementation can also be implemented separately in multiple implementations or in any suitable partial combination. Additionally, although features may be described as acting in a particular combination, one or more features from the claimed combination can, in some cases, be deleted from that combination, and the combination can be claimed as a partial combination or a variation of a partial combination.

[0307] Moreover, operations may be shown in the drawings or described herein in a particular order, but such operations need not be performed in the particular order shown or in a sequential order to achieve desirable results, nor is it necessary that all operations be performed. Other operations not shown or described can be incorporated into the exemplary methods and processes. For example, one or more additional operations can be performed before, after, simultaneously with, or between any of the described operations. Further, the operations may be rearranged or ordered differently in other embodiments. In some embodiments, those skilled in the art will understand that the actual steps taken in the illustrated and / or disclosed processes may differ from those shown in the figures. Depending on the embodiment, certain of the steps described above may be deleted, and other steps may be added. Additionally, the features and attributes of the specific embodiments disclosed above can be combined in different ways to form additional embodiments, all of which fall within the scope of this disclosure. Further, the separation of the various system components in the implementations described above should not be understood to be required in all implementations, and it should be understood that the components and systems described are generally either integrated together in a single product or can be packaged in multiple products.

[0308] For purposes of the present disclosure, certain aspects, advantages, and novel features are described herein. Not all such aspects or advantages may necessarily be achieved in accordance with any particular embodiment. Thus, for example, those skilled in the art will recognize that the present disclosure may be embodied or carried out without necessarily achieving one advantage or group of advantages as taught herein, without necessarily achieving other advantages as may be taught or suggested herein.

[0309] Conditional language, such as “can,” “could,” “might,” or “may,” unless specifically stated otherwise or understood otherwise within the context in which it is used, generally is intended to convey that a particular embodiment includes, but other embodiments do not include, a particular feature, element, and / or step. Thus, such conditional language generally is not intended to imply that a feature, element, and / or step is in any way required for one or more embodiments or that one or more embodiments necessarily include logic for determining whether these features, elements, and / or steps are included in, or are to be performed in, any particular embodiment, whether or not user input or prompting is present.

[0310] Conjunctive language, such as the phrase “at least one of X, Y, and Z,” unless specifically stated otherwise, is generally understood within the context used to convey that an item, term, etc. may be either X, Y, or Z. Thus, such conjunctive language is not generally intended to imply that a particular embodiment requires the presence of at least one of each of X, at least one of each of Y, and at least one of each of Z.

[0311] Languages such as the terms "about", "approximately", "substantially", and "essentially" as used in this specification still represent values, amounts, or characteristics that are close to the recited values, amounts, or characteristics that still perform the desired function or achieve the desired result. For example, the terms "about", "approximately", "substantially", and "essentially" can refer to amounts that are less than 10%, less than 5%, less than 1%, less than 0.1%, and less than 0.01% of the recited amount. As another example, in certain embodiments, the terms "substantially parallel" and "essentially parallel" refer to values, amounts, or characteristics that deviate from exact parallelism by 15 degrees, 10 degrees, 5 degrees, 3 degrees, 1 degree, or 0.1 degree or less.

[0312] The scope of the present disclosure is not intended to be limited by the specific disclosure of the preferred embodiments in this section or elsewhere in this specification, but rather may be defined by the claims, as presented in this section or elsewhere in this specification, or as may be presented in the future. The language of the claims should be construed broadly based on the language used in the claims and not limited to the examples described during the implementation of this specification or this application, and the examples should be construed as non-exclusive.

Claims

1. A patchless device for treating eye tissue, a device suitable for applying an adhesive and dimensioned to advance into the eye, a bioadhesive substance in the form of a bubble, the bioadhesive substance surrounding a gas, the bubble being held by the device, the bioadhesive substance and the device being configured such that when the surface of the eye contacts the bubble, the bioadhesive substance can be moved from the device to the surface of the eye, the bioadhesive substance being configured to cover the entire eye tissue within a retinal defect without applying a patch, a bioadhesive substance; A patchless device comprising the above.

2. The device is a cannula including a proximal end portion, a distal end portion, and an intermediate portion extending therebetween, a distal tip at the distal end portion of the cannula, the distal tip having a bubble support surface and an outlet port extending through the bubble support surface, an inflation fluid passage extending through at least the intermediate portion and the distal portion of the cannula, the inflation fluid passage being in fluid communication with the outlet port; The device according to claim 1.

3. The device is an inflation fluid source, an actuator coupled to the inflation fluid source and configured to selectively advance the inflation fluid through the inflation fluid passage and the outlet port upon actuation of the actuator; The device according to claim 2, further comprising the above.

4. In an operable state, the device is configured such that at least one bubble of the substance is formed from the layer of the substance on the bubble support surface of the distal tip by advancing the inflation fluid from the inflation fluid source through the outlet port. The device according to any one of the preceding claims.

5. The device according to claim 2, wherein the bubble support surface comprises a retaining ridge, lip and / or rim configured to support the bubble.

6. The device according to claim 2, further comprising a substance supply channel configured to supply the bioadhesive substance to the distal tip of the device.

7. The device according to claim 6, wherein the substance supply channel is in fluid communication with a substance supply source.

8. A patchless device for treating eye tissue, A device suitable for applying an adhesive, dimensioned to advance into the eye, comprising an applicator portion having a surface that is generally wide and flat and has a width and length greater than its thickness, a bioadhesive substance held across the surface of the applicator portion, wherein the bioadhesive substance and the device are configured such that when the surface of the eye is brought into contact with the bioadhesive substance on the surface of the applicator portion, the bioadhesive substance can be moved from the device to the surface of the eye, and the bioadhesive substance is configured to cover the entire eye tissue within the retinal defect without applying a patch, A patchless device comprising: **Claim 9** The device is a sleeve having a proximal end, a distal end, and a passage extending along the length of the sleeve from the proximal end to the distal end of the sleeve, an applicator comprising an elongate body and an applicator tip coupled to the distal end of the elongate body, wherein the elongate body is movable within the sleeve, and the applicator portion of the applicator tip is self-expanding from a first collapsed state to a second expanded state when it exits the distal end of the sleeve, The device according to claim 8, comprising: **Claim 10** The applicator tip includes an elongate portion and the applicator portion, and the elongate portion of the applicator tip has an applicator tip passage extending therethrough from the proximal end to the distal end of the elongate portion, and the applicator tip passage is in fluid communication with the passage of the elongate body at the proximal end of the elongate portion in an operable state. The device according to claim 9. **Claim 11** One or more openings are formed through a first surface of the applicator portion, and the openings or orifices are in fluid communication with the applicator tip passage. The device according to claim 10. **Claim 12** The passage through at least the elongate portion of the applicator tip is i. an opening at the proximal end of the applicator portion, or ii. a plurality of openings passing through the first surface of the applicator portion, or iii. both the opening at the proximal end of the applicator portion and the plurality of openings passing through the first surface of the applicator portion, The device according to claim 10, which is in communication with **Claim 13** The applicator portion is configured such that when the elongated body and the applicator tip are drawn into the sleeve from the second expanded state to the first crushed state, the applicator can be drawn through the opening in the tissue with the applicator tip retracted into the sleeve, and the applicator portion is configured to crush into a more compact or narrower shape. The device according to claim 9. **Claim 14** The device according to claim 8, comprising a substance supply conduit extending along the length of the device through which the bioadhesive substance can pass, such that the bioadhesive substance can be applied at least to the applicator portion. **Claim 15** The device according to claim 13, further comprising a source of the bioadhesive substance in fluid communication with at least the substance supply conduit.

Images