Methods for creating and maintaining blebs via electroporation and associated systems and devices

Abstract

The present technology is generally directed to methods for creating and maintaining blebs via electroporation, and associated systems and devices. Electroporation assemblies disclosed herein are configured to engage a bleb on an eye, such as from within or on an outer surface of the bleb, and generate an electric field that may be controlled to provide reversible electroporation or irreversible electroporation to the bleb. Electroporation assemblies can include an electrode assembly and an electrode delivery device, such as a needle, that assist with engaging the electrode assembly with the bleb. The electroporation provided is expected to improve drug delivery and reduce scarring by interfering with the natural healing process of the bleb.

Description

METHODS FOR CREATING AND MAINTAINING BLEBS VIA ELECTROPORATION AND ASSOCIATED SYSTEMS AND DEVICESCROSS-REFERENCE TO RELATED APPLICATION^ )

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 580,854, filed September 6, 2023, and which is incorporated herein by reference in its entirety.TECHNICAL FIELD

[0002] The present technology generally relates to medical treatment and, in particular, to methods for creating and maintaining blebs via electroporation.BACKGROUND

[0003] Glaucoma treatment surgery, such as trabeculectomy or implantation of a shunting system, may involve creation of a bleb, a small, blister-like elevation that forms on the surface of the eye. The bleb can serve as a target outflow location for shunting systems to shunt fluid from a portion of the eye, such as the anterior chamber, to help reduce intraocular pressure. However, the creation of a bleb can trigger an inflammatory or immune response and the normal healing process of the eye can result in the development of fibrosis and eventual scarring. The development of fibrosis can be problematic because, for example, fibrosis can cause the bleb to cease draining fluid and therefore fail to decrease intraocular pressure (IOP). Conventional methods to interfere with bleb healing and scarring include, for example, pre-procedural Beta radiation treatment, the use of antiproliferatives or steroids, and / or the application of direct heat or radio fields. Such methods, however, can be invasive and are often associated with side effects such as significant inflammatory responses and cataract development.BRIEF DESCRIPTION OF THE DRAWINGS

[0004] Many aspects of the present technology can be better understood with reference to the following drawings. The components in the drawings are not necessarily drawn to scale. Instead, emphasis is placed on illustrating clearly the principles of the present technology'. Furthermore, components can be show n as transparent in certain views for clarity’ of illustration only and not to indicate that the component is necessarily transparent. Components may also be shown schematically.

[0005] FIG. 1 is a cross-sectional view of a shunt implanted in an eye in accordance with an embodiment of the present technology.

[0006] FIGS. 2A and 2B are perspective cut-out and cross-sectional views, respectively, of an electroporation assembly inserted in an eye in accordance with an embodiment of the present technology.

[0007] FIGS. 3A and 3B are enlarged perspective and enlarged plan views, respectively, of an electroporation assembly configured in accordance with an embodiment of the present technology7.

[0008] FIG. 3C is a perspective view of the electroporation assembly of FIG. 3 A.

[0009] FIG. 4A is a perspective view of an electroporation assembly configured in accordance with another embodiment of the present technology7.

[0010] FIGS. 4B and 4C are enlarged plan views of the electroporation assembly of FIG. 4A.

[0011] FIGS. 5A and 5B are perspective and plan views, respectively, of an electroporation assembly configured in accordance with another embodiment of the present technology.

[0012] FIG. 6A is a plan view of an electroporation assembly configured in accordance with another embodiment of the present technology.

[0013] FIG. 6B is a plan view of an electroporation assembly configured in accordance with another embodiment of the present technology.DETAILED DESCRIPTION

[0014] The present technology7is generally directed to minimally-invasive systems and methods for creating and maintaining blebs via electroporation. Electroporation is the application of an electrical current across a cell membrane, resulting in temporary, semipermanent, or permanent pores. The pores allow exogenous molecules, such as DNA, RNA, drugs, or other substances, to pass into the cytoplasm (transient transfection) and / or the nucleus (stable transfection) more easily than they would under normal conditions. Semi-permanent and permanent pores can also lead to cell death via leakage of cytoplasm and / or other mechanisms. As described herein, electroporation assemblies configured in accordance with the present technology7can include an electrode assembly adapted to generate an electric field and anelectrode delivery' device for engaging the electrode assembly with a bleb. The generated electric field can be controlled to provide reversible electroporation or irreversible electroporation to the bleb. In this way, the systems and methods described herein are expected to improve drug delivery and reduce scarring by interfering with the natural healing process of the bleb, such as by killing cells associated with scarring of the bleb.

[0015] In some embodiments, an electrode delivery' device can include a delivery needle configured to pierce a bleb membrane and provide a pathway for the electrode assembly to enter inside the bleb. The electrode delivery device may also be configured for use with a guide wire to guide the electrode assembly into the bleb and retain a desired shape. In some embodiments, the electrode assembly can be arranged on a chip configured to be positioned proximate to an outer surface of the bleb during operation of the electroporation assembly.

[0016] As described in further detail below, electroporation assemblies configured in accordance with the present technology can be operated to induce electroporation prior to bleb creation (e.g., as a pretreatment), during bleb creation, and / or after bleb creation (e.g., during maintenance of the bleb). Electroporation assemblies can also induce either reversable electroporation (e.g., for enhanced drug delivery') or irreversible electroporation (e.g., for interfering with normal healing processes). For example, a pretreatment can include a reversable electroporation procedure in conjunction with the delivery of antiproliferative drugs, followed by an irreversible electroporation procedure. In another example, irreversible electroporation can be provided at the surface of the eye pre-procedurally for an initial evaluation. In another example, during bleb creation, the electroporation assembly can serve as a replacement for or used in conjunction with antiproliferatives and / or steroids. Electroporation assemblies configured in accordance with the present technology can also serve as a replacement for needling, which is expected to mitigate / reduce injuries to the eye associated with needling that can, in some instances, eventually lead to scarring.

[0017] By interfering with the natural healing process of the bleb, the electroporation process is expected to maintain or increase the perfusion or diffusion of aqueous from the bleb into and / or across one or more of the conjunctival and episcleral vasculature, and the conjunctival epithelium. In some embodiments, electroporation assemblies configured in accordance with the present technology can be used to target certain cells in order to promote a specific healing response or pattern that is more conducive to removing fluids through the bleb. For example, fibroblast cells, which are at least partly responsible for the development of scartissue, can be targeted during the proliferation stage. Furthermore, compared to conventional methods for creating and maintaining blebs, such as direct physical interaction such as needling, electroporation induces a reduced inflammatory or immune response.

[0018] The terminology used in the description presented below is intended to be interpreted in its broadest reasonable manner, even though it is being used in conjunction with a detailed description of certain specific embodiments of the present technology. Certain terms may even be emphasized below; however, any terminology intended to be interpreted in any- restricted manner will be overtly and specifically defined as such in this Detailed Description section. Additionally, the present technology can include other embodiments that are within the scope of the claims, but are not described in detail with respect to FIGS. 1-6B.

[0019] Reference throughout this specification to '‘one embodiment” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present technology. Thus, the appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features or characteristics may be combined in any suitable manner in one or more embodiments.

[0020] As used herein, the use of relative terminology', such as “about,” “approximately,” “substantially” and the like refer to the stated value plus or minus ten percent. For example, the use of the term “about 100” refers to a range of from 90 to 110. inclusive. In instances in which the context requires otherwise and / or relative terminology is used in reference to something that does not include a numerical value, the terms are given their ordinary' meaning to one skilled in the art.

[0021] FIG. 1 is a cross-sectional view of a shunting system 100 implanted in an eye 102 in accordance with an embodiment of the present technology. The eye 102 can include lens 110, pupil 112, iris 116, anterior chamber 114. cornea 118, trabecular meshwork 126, zonules 120, ciliary body 122, sclera 124, Tenon’s capsule 132, and conjunctiva 130. A bleb 104 can be formed (e.g., via operation) between any adjacent ones of the conjunctiva 130, the Tenon’s capsule 132, the sclera 124, or other layers (e.g., the episcleral layer, the scleral stroma layer). For example, the bleb 104 can be formed below the conjunctiva 130 (e.g., a subconjunctival bleb) which, in some specific embodiments, can be about 0.047 mm from the surface of the eye102. In another example, the bleb 104 can be formed at the scleral episcleral boundary which, in some specific embodiments, can be about 0.6 mm from the surface of the eye 102.

[0022] In some embodiments, the shunting system 150 can include an actuation assembly 152 positioned at a distal end of the shunting system 150 configured to be implanted in the anterior chamber 1 14. In some embodiments, the shunting system 150 can include a flange region 154 to allow the shunting system 150 to conform to the shape of (e.g., by bending) and / or minimize migration within the eye 102 and its layers. The shunting system 150 can be positioned to extend between the anterior chamber 114 and the bleb 104. Once implanted in the eye 102, the shunting system 150 can direct fluid flow (e.g., aqueous) from the anterior chamber 114 (or elsewhere) toward the bleb 104, which can serve as a distribution point for enhanced fluid removal. Additional details regarding suitable shunting systems are described in U.S. Patent Nos. 11,166, 849and 11,291,585, and International Patent ApplicationNos. PCT / US2021 / 049140, PCT / US2022 / 037747, and PCT / US2022 / 037917, each of which is incorporated by reference herein in its entirety.

[0023] In some instances, the natural healing processes of the bleb 104, however, may progress such that the bleb’s ability’ to drain aqueous is diminished, such as by scarring. For example, fibrosis can develop inside or around the shunting system 150 and / or the bleb 104 and prevent fluid outflow. Therefore, it is desirable to maintain patency of the bleb 104. As described in further detail below, an electroporation assembly 106 configured in accordance with embodiments of the present technology can be engaged with a target area (e.g., pre-procedurally at an area at which a bleb is to be formed, post-operation at the bleb site) in order to interfere with the natural healing processes of the bleb that can result in the formation of scar tissue and or impermeable blebs. The electroporation assembly 106 can be positioned proximate the bleb 104 at the surface of the eye 102 (as shown), inside the bleb 104, or elsewhere.

[0024] FIGS. 2A and 2B are perspective cut-out and cross-sectional views, respectively, of an electroporation assembly 200 inserted in an eye 202 and configured in accordance with an embodiment of the present technology7. More specifically, the electroporation assembly 200 is shown inserted at least partially inside a bleb 204 (e.g., a subconjunctival bleb space). The electroporation assembly 200 can comprise an electrode assembly 210 and an electrode delivery device 220 configured to facilitate minimally invasive delivery of the electrode assembly 210 to the eye 202. In the illustrated embodiment, for example, the electrode delivery- device 220 comprises a delivery needle through which the electrode assembly 210 can translate. As shownin FIG. 2B. the delivery' needle 220 can pierce the bleb 204 while the electrode assembly 210 is in a retracted state (e.g., not extending beyond the tip of the delivery’ needle). Once the tip of the delivery needle 220 is at a suitable position within the bleb 204, the electrode assembly 210 can be pushed through the needle 220 to extend in a desired configuration within the bleb 204, as shown in FIG. 2A. In the illustrated embodiment, the electrode assembly 210 extends in a spiraling pattern. In other embodiments, the electrode assembly 210 can extend in other patterns (e.g.. straight, curved, rectangular, circular, elliptical, etc.). Any desired length of the electrode assembly^ 210 can be delivered to the bleb 204. In some embodiments, the electrode assembly 210 comprises one or more nitinol wires optionally coated with silver, gold, or other material to enhance conductivity'.

[0025] During operation of the electroporation assembly 200, current can be delivered from a power source (not shown) through the electrode assembly 210 such that the current flowing therein generates an electric field within and / or around the bleb 204. In some embodiments, the electroporation assembly' 200 can be configured to induce reversable electroporation and / or irreversible electroporation. When inducing irreversible electroporation, the generated electric field can interfere with the natural healing process of the bleb 204. For example, the induced irreversible electroporation can damage or kill tissue cells within and surrounding the bleb 204 that are expected to result in the formation of scar tissue and / or impermeable blebs. Upon termination of an electroporation session, the electrode assembly 210 can be retracted back through the delivery needle 220, and the delivery needle 220 can then be removed from the patient.

[0026] When providing reversable electroporation therapy, the current and / or voltage can be controlled such that the electrodes generate an electric field gradient (EFG) of, e.g., less than about 500 V / cm across a cell membrane (or across any molecular bilayer membrane). The generated electric field is expected to create pores in the membrane that are small enough to be healed at a sufficient rate, precluding drainage of excessive cytoplasm from the cell (hence the “reversible” nature of the electroporation). In some embodiments, reversable electroporation can be used to allow exogenous molecules (e.g., surface-bound molecules) that are too large to pass through the cellular bilayer membrane under normal circumstances to pass through. For example, reversible electroporation can create pores that allow' large antiproliferative drug molecules to enter the cells. In some embodiments, reversable electroporation can be used as a targeted drug delivery mechanism. For example, the electric field can be applied to certain cells or certain regions of cells such that antiproliferative or other drug molecules of sufficiently largesizes only enter those targeted cells. Moreover, because certain cells can be targeted and the permeability of the cells is increased, reversible electroporation can allow for a lower concentration of drugs to be initially delivered to the patient, reducing the risks associated with high dosage of such drugs. In other embodiments, however, the delivered current and / or voltage associated with reversable electroporation can vary7.

[0027] When providing irreversible electroporation therapy, the current and / or voltage can be controlled such that the electrodes generate an EFG of, e.g., greater than about 500 V / cm across a cell membrane (or across any molecular bilayer membrane). The generated electric field creates pores in the membrane that are too large to be healed or healed at a sufficient rate, allowing drainage of excessive cytoplasm from the cell and / or other mechanisms and potentially killing the cell (hence the “irreversible” nature of the electroporation). In some embodiments, irreversible electroporation can be used to reduce or minimize short-term inflammation by eliminating the local supply of cells that are responsible for initiating the normal inflammatory response, thereby reducing or minimizing long-term scarring. In other embodiments, the delivered current and / or voltage associated with irreversible electroporation can vary7.

[0028] As discussed above with respect to FIG. 1, the bleb 204 can form below the conjunctiva layer (e.g., a subconjunctival bleb). In some specific embodiments, for example, this is about 0.047 mm from the surface of the eye. at the scleral episcleral boundary that is about 0.6 mm from the surface of the eye, or anywhere in between. When providing reversable electroporation (e g., EFG of about 500 V / cm), in some embodiments the voltage applied across the electrode assembly 210 can be, for example, about 3.5 V if applied to a subconjunctival bleb via electrodes on the surface, about 47 V if applied to a bleb at the scleral episcleral boundaryvia electrodes on the surface, and about 3.5 V if applied from within the bleb. When providing irreversible electroporation (e.g., EFG of about 1000 V / cm), in some embodiments the voltage applied across the electrodes can be, for example, about 7 V if applied to a subconjunctival bleb via electrodes on the surface, about 94 V if applied to a bleb at the scleral episcleral boundary7via electrodes on the surface, and about 7 V if applied from within the bleb. In further embodiments, however, the applied voltages can vary. As will be discussed in greater detail below, FIGS. 3A-4C illustrate embodiments of subsurface electroporation assemblies, and FIGS. 5A-6B illustrate embodiments of surface electroporation assemblies.

[0029] As mentioned previously, the electroporation assembly 200 can be operated to provide electroporation therapy prior to bleb creation (e.g., as a pretreatment), during blebcreation, and / or during maintenance of the bleb. For example, a pretreatment can include a reversable electroporation procedure in conjunction with delivery of antiproliferative drugs. In another example, the delivery of antiproliferative drugs can be followed by an irreversible electroporation procedure. In another example, only an irreversible electroporation procedure is performed. In another example, irreversible electroporation can be provided at the surface of the eye pre-procedurally for an initial evaluation. In another example, during bleb creation, the electroporation assembly can serve as a replacement for or used in conjunction with antiproliferatives and / or steroids. The electroporation assembly 200 can also serve as a replacement for needling, which is expected to mitigate / reduce injuries to the eye associated with needling that can, in some instances, eventually lead to scarring.

[0030] In yet another example, electroporation therapy can be provided after creation and during the healing process of the bleb 204. The normal healing process of a bleb can be divided into four stages: (a) inflammation, (b) proliferation, (c) remodeling, and (d) scarring. During the inflammation stage, the concentration of cells sent to the bleb by the immune system can cause swelling. During the proliferation stage, fibroblast cells can begin to form, grow, and multiply within the bleb. During the remodeling stage, the fibroblast cells can continue to grow and lead to the development of fibrosis. At the scarring stage, the fibrosis can further develop into scars, which is undesirable in the bleb context.

[0031] The electroporation assembly 200 can be operated to provide electroporation therapy to the bleb 204 at one or more of the four healing stages to minimize the development of fibrosis and / or the eventual generation of scar tissue. By interfering with the healing process, the electroporation therapy is expected to reduce the perfusion or diffusion of aqueous from the bleb 204 into and / or across one or more of the conjunctival and episcleral vasculature, and the conjunctival epithelium. In some embodiments, the electroporation assembly 200 can be used to target certain cells to promote a specific healing response or pattern that is more conducive to removing fluids through the bleb 204. For example, fibroblast cells that are at least partly responsible for the development of scar tissue can be targeted during the proliferation stage. Furthermore, compared to conventional methods for creating and maintaining blebs, such as the application of direct heat and / or radio fields, electroporation is expected to induce a reduced inflammatory and / or immune response.

[0032] FIGS. 3A and 3B are enlarged perspective and enlarged plan views, respectively, of a subsurface electroporation assembly 300 configured in accordance with an embodiment ofthe present technology. FIG. 3C is a perspective view of the subsurface electroporation assembly 300. In some embodiments, the electroporation assembly 300 can be an example of the electroporation assembly 200 illustrated in FIGS. 2A and 2B.

[0033] Referring to FIGS. 3A-3C together, the electroporation assembly 300 comprises an electrode assembly 310 and an electrode delivery device 320. The electrode assembly 310 can comprise a first electrode 312, a second electrode 314, and an insulator 316 disposed between the first and second electrodes 312, 314. As best seen in FIG. 3B, in the illustrated embodiment, a gap 318 is maintained in between the first and second electrodes 312, 314. In some embodiments, a width of the gap 318 can range between, for example, 50 pm and 250 pm. In other embodiments, however, the gap 318 may have different dimension and / or may vary along its length. In some embodiments, the insulator 316 can extend at least partially within the gap 318. As shown in FIG. 3C, the electrode delivery device 320 comprises a delivery needle through which the electrode assembly 310 can translate.

[0034] As discussed above with respect to FIGS. 2A and 2B, during operation of the electroporation assembly 300, the delivery needle 320 can pierce a bleb while the electrode assembly 310 is in a retracted state (e.g., not extending beyond the tip of the delivery needle, maintaining a narrow footprint). Once the tip of the delivery' needle 320 is at a suitable position within the bleb space, the electrode assembly 310 can be pushed through the needle 320 to extend in a desired configuration within the bleb space. In the embodiment illustrated in FIGS. 3A-3C, for example, the first and second electrodes 312, 314 extend in a spiraling pattern, allowing the first and second electrodes 312, 314 to cover a large portion of the bleb area. In other embodiments, the first and second electrodes 312, 314 can extend in other patterns (e.g.. straight, curved, rectangular, circular, elliptical, etc.). Any desired length of the first and second electrodes 312, 314 can be delivered to the bleb space. In some embodiments, a voltage that ranges between 5 V and 35 V can be applied across the first and second electrodes 312, 314 depending on, for example, whether reversible or irreversible electroporation is desired. Upon termination of an electroporation therapy, the electrode assembly 310 can be retracted back through the delivery needle 320, and the delivery needle 320 can then be removed from the bleb.

[0035] FIG. 4A is a perspective view of a subsurface electroporation assembly 400 configured in accordance with another embodiment of the present technology. FIGS. 4B and 4C are enlarged plan views of the electroporation assembly 400. In some embodiments, the electroporation assembly 400 can be an example of the electroporation assembly 200 illustratedin FIGS. 2A and 2B. Referring to FIGS. 4A-4C together, the electroporation assembly 400 comprises an electrode assembly 410 and an electrode delivery device 420. The electrode assembly 410 can include a moveable electrode component 416 having a lumen 411 extending therethrough, a first electrode 412 on the moveable electrode component 416, and a second electrode 414 on the moveable electrode component 416. The first electrode 412 is spaced apart from the second electrode 414 by a gap 418. In some embodiments, a width of the gap 418 can range between 50 pm and 250 pm. In other embodiments, however, the gap 418 may have other dimensions. . The electrode delivery device 420 is configured to be delivered over a guide wire 420. The guide wire 420 can be positioned to extend through the lumen 411 of the moveable electrode component 416.

[0036] During operation of the electroporation assembly 400, the guide wire 420 can pierce a bleb while the electrode assembly 410 remains outside of the bleb. The guide wire 420 can continue to be inserted into the bleb until a sufficient length of the guide wire 420 is in a desired pattern. In the illustrated embodiment, the guide wire 420 extends in a spiraling pattern. In other embodiments, the guide wire 420 can extend in other patterns (e.g., straight, curved, rectangular, circular, elliptical, etc.). Any desired length of the guide wire 420 can be delivered to the bleb space.

[0037] The moveable electrode component 416 can then be pushed or otherwise translated along the guide wire 420 until the moveable electrode component 416 is in the same shape as the guide wire 420 within the bleb space. As the moveable electrode component 416 is translated, the first and second electrodes 412, 414 can be energized to generate an electric field. The first and second electrodes 412. 414 can be energized continuously and / or at discrete positions along the guide wire 420. In some embodiments, a voltage that ranges between 5 V and 35 V can be applied across the first and second electrodes 412, 414 depending on, for example, whether reversible or irreversible electroporation is desired. Upon termination of an electroporation session, the moveable electrode component 416 can be moved along the guide wire 420 to outside of the bleb, and the guide wire 420 can then be removed from the bleb.

[0038] In some embodiments, features of the electroporation assembly 300 illustrated in FIGS. 3A-3C can be combined with features of the electroporation assembly 400 illustrated in FIGS. 4A-4C. For example, two elongated electrodes (e g., the first and second electrodes 312, 314) can be positioned along a moveable electrode component (e.g., the moveable electrode component 416. In another example, an electroporation assembly can comprise a first electrodedelivery device comprising a delivery needle (e.g., the delivery needle 320) and a second electrode delivery device configured to be delivered via a guide wire (e.g., the guide wire 420). The electrodes can be mounted along the guide wire, and the electrodes and the guide wire can be positioned within the needle. During operation, the needle can be used to pierce the bleb, the guide wire can be extended within the bleb to a desired length and pattern, and the electrodes can be slid along between the needle and the guide wire to within the bleb. The electroporation assembly can then provide reversible or irreversible electroporation.

[0039] FIGS. 5A and 5B are perspective and plan views, respectively, of a surface electroporation assembly 500 configured in accordance with another embodiment of the present technology. The electroporation assembly 500 comprises a chip 520 having a first end portion 522 and a second end portion 524 opposite the first end portion 522. The electroporation assembly 500 further includes a plurality of surface electrodes 512 (individually labeled 512a, 512b. 512c, 512d, etc.) on a top surface of the first end portion 522, and a plurality of electrode contacts 514 (individually labeled 514a, 514b, 514c, 514d, etc.) on a top surface of the second end portion 524. The first end portion 522 of the chip 520 can include a through hole 526. The top surface of the first end portion 522 can be substantially flat or have a curvature (e.g., corresponding to the curvature of an average bleb). In the illustrated embodiment, individual ones of the surface electrodes 512 have annular shapes with varying diameters and are arranged concentric with the hole 526 and with one another. In other embodiments, the surface electrodes 512 can have other shapes and / or arranged in a different pattern.

[0040] In some embodiments, the surface electrodes 512 can be arranged with gaps 518 therebetween. The gaps 518 can range in width, for example, between 50 pm and 250 pm. In some embodiments, the surface electrodes 512 can be at least partially embedded in the first end portion 522 of the chip. Similarly, the electrode contacts 514 can be arranged with gaps 519 therebetween and / or at least partially embedded in the second end portion 524. Individual ones of the surface electrodes 512 can be electrically coupled to corresponding ones of the electrode contacts 514 via, for example, wires (not shown) embedded in the chip 520 or disposed on a bottom surface of the chip 520. In some embodiments, the number of surface electrode and electrode contact pairs can be at least one, two, three, four, five, six, seven, eight, nine, ten, fifteen, twenty, or more. The chip 520 can be made from a non-conductive and / or biocompatible material, such as elastomers (e.g., silicone, polyurethane), polyether ether ketone (PEEK), and polyethylene terephthalate (PET).

[0041] During operation, the electroporation assembly 500 can be positioned on a patient's eye such that the surface electrodes 512 contact or are disposed adjacent a bleb. Individual ones of the electrode contacts 514 can be electrically coupled to a power source (not shown). Current can flow from the electrode contacts 514 to corresponding ones of the surface electrodes 512 to generate an electric field around the bleb to provide electroporation therapy. In some embodiments, the power source is further operatively coupled to a controller (not shown) such that the controller can individually control power output to each of the electrode contacts 514. By individually controlling the power outputs, the strength and shape of the electric field produced by the surface electrodes 512 can be varied and controlled. As described above, by controlling the electric field, the electroporation assembly 500 can be used to target certain cells to promote a specific healing response or pattern that is more conducive to removing fluids through the bleb. In some embodiments, fluid can be removed from the bleb through the hole 526 (e.g., via a vacuum suction force). Upon termination of an electroporation session, the chip 520 can be removed from the patient.

[0042] FIG. 6A is a plan view of an electroporation assembly 600 configured in accordance with still another embodiment of the present technology. The electroporation assembly 600 can include a chip 620 having a first end portion 622 and a second end portion 624 opposite the first end portion 622. The electroporation assembly 600 also includes a first surface electrode 612a and a second surface electrode 612b (collectively ‘‘surface electrodes 612”) on a top surface of the first end portion 622, and a first electrode contact 614a and a second electrode contact 614b (collectively “electrode contacts 614”) on a top surface of the second end portion 624. The first end portion 622 of the chip 620 can include a through hole 626. The top surface of the first end portion 622 can be substantially flat or have a curvature (e.g., corresponding to the curvature of an average bleb). In the illustrated embodiment, the surface electrodes 612 are arranged in an interleaved pattern. In other embodiments, the surface electrodes 612 can have other shapes and / or arranged in a different pattern.

[0043] In some embodiments, the surface electrodes 612 can be arranged with a gap 618 therebetween, which can range in width, for example, between 50 pm and 250 pm. In some embodiments, the surface electrodes 612 can be at least partially embedded in the first end portion 622 of the chip 620. Similarly, electrode contacts 614 can be arranged with a gap therebetween. The first surface electrode 612a can be electrically coupled to the first electrode contact 614a via a first wire 616a, and the second surface electrode 612b can be electrically coupled to the second electrode contact 614b via a second wire 616b. The first and / or the secondwires 616a, 616b can be exposed on the top surface of the chip 620 (as shown) and / or at least partially embedded within the chip 620. In some embodiments, the number of surface electrode 612 and electrode contact pairs 614 can be at least one, two, three, four, five, six, seven, eight, nine, ten, fifteen, twenty, or more. The chip 620 can be made from a non-conductive material.

[0044] During operation, the electroporation assembly 600 can be positioned on a patient’s eye such that the surface electrodes 612 make contact with or are disposed adj acent a bleb. Each of the electrode contacts 614 can be electrically coupled to a power source (not shown). Current can flow from the electrode contacts 614 to corresponding ones of the surface electrodes 612 to generate an electric field around the bleb to provide electroporation. In some embodiments, the power source is further operatively coupled to a controller (not shown) such that the controller can individually control power output to each of the electrode contacts 614. By individually controlling the power outputs, the strength and shape of the electric field produced by the surface electrodes 612 can be varied and controlled. As described above, by controlling the electric field, the electroporation assembly 600 can be used to target certain cells to promote a specific healing response or pattern that is more conducive to removing fluids through the bleb. In some embodiments, fluid can be removed from the bleb through the hole 626 (e.g., via a vacuum suction force). Upon termination of an electroporation session, the chip 620 can be removed from the vicinity of the bleb.

[0045] FIG. 6B is a plan view of an electroporation assembly 601 configured in accordance with yet another embodiment of the present technology. The electroporation assembly 601 can include a chip 621 having a first end portion 623 and a second end portion 625 opposite the first end portion 623. The electroporation assembly 601 also includes a first plurality of surface electrodes 613a and a second plurality of surface electrodes 613b (collectively “surface electrodes 613”) at the first end portion 623 of the chip 621, and a first electrode contact 615a and a second electrode contact 615b (collectively “electrode contacts 615”) at the second end portion 625 of the chip 621. The first end portion 623 of the chip 621 can include a through hole 627. The top surface of the first end portion 623 can be substantially flat or have a curvature (e.g., corresponding to the curvature of an average bleb). In the illustrated embodiment, each of the surface electrodes 613 have circular shapes and are arranged such that the first and second pluralities of surface electrodes 613a, 613b alternate along each row and column. In other embodiments, however, the surface electrodes 613 can have other shapes and / or be arranged in a different pattern.

[0046] In some embodiments, individual ones of the surface electrodes 613 can be spaced apart by a distance that ranges, for example, between 50 pm and 250 pm. In some embodiments, at least some of the surface electrodes 613 can be at least partially embedded in the first end portion 623 of the chip 621. Similarly, the electrode contacts 615 can be arranged with a gap therebetween. The chip 621 can be made from a non-conductive material. The first plurality of surface electrodes 613a can be electrically coupled to the first electrode contact 615a via a first wire (not shown), and the second plurality of surface electrodes 613b can be electrically coupled to the second electrode contact 615b via a second wire (not shown). The first and / or the second wires can be exposed on the top surface of the chip 621 and / or at least partially embedded within the chip 621. In some embodiments, the number of surface electrode and electrode contact pairs can be at least one. two, three, four, five, six, seven, eight, nine, ten, fifteen, twenty, or more.

[0047] During operation, after delivery of the electroporation assembly 601 to a patient's eye such that the surface electrodes 613 make contact with or are disposed adjacent a bleb, current can flow from each of the electrode contacts 615 to corresponding ones of the surface electrodes 613 to generate an electric field around the bleb to provide electroporation. In some embodiments, the power source (not shown) operably coupled to the electrode contacts 615 is further operatively coupled to a controller (not shown) such that the controller can individually control power output to each of the electrode contacts 615. As noted previously, by individually controlling the power outputs, the strength and shape of the electric field produced by the surface electrodes 613 can be varied and controlled, thereby allowing the electroporation assembly 601 to target certain cells to promote a specific healing response or pattern that is more conducive to removing fluids through the bleb. In some embodiments, fluid can be removed from the bleb through the hole 627 (e.g., via a vacuum suction force). Upon termination of electroporation therapy, the chip 621 can be removed from the patient.

[0048] In some embodiments, features of the electroporation assembly 500 illustrated in FIGS. 5A and 5B can be combined with features of the electroporation assemblies 600. 601 illustrated in FIGS. 6A and / or 6B. For example, an electroporation assembly can comprise a plurality of surface electrodes (e.g., more than two, such as the surface electrodes 512) and two electrode contacts (e.g., the electrode contacts 614). A first one of the electrode contacts (e.g., 614a) can be electrically coupled to odd ones of the surface electrodes (e.g., 512a, 512c, etc.) and a second one of the electrode contacts (e.g., 614b) can be electrically coupled to even ones of the surface electrodes (e.g.. 512b, 512d, etc.). Any other pairing between the surfaceelectrodes and the electrode contacts are possible. It is also appreciated that any number of surface electrodes can be paired with any number of electrode contacts.Examples

[0049] Several aspects of the present technology are set forth in the following examples:1. A method for maintaining a bleb within an eye of a patient in the treatment of glaucoma, the method comprising: delivering an electroporation assembly to a target treatment area in a bleb within an eye of the patient, wherein the electroporation assembly comprises an electrode assembly; and generating an electric field via the electrode assembly to induce electroporation in at least a portion of the target treatment area, thereby minimizing the development of fibrosis and / or reducing generation of scar tissue in the target treatment area.2. The method of example 1 wherein the generated electric field has an electric field gradient less than about 500 V / cm, and wherein the electroporation therapy comprises reversible electroporation.3. The method of example 1 wherein the generated electric field has an electric field gradient greater than about 500 V / cm, and wherein the electroporation therapy comprises irreversible electroporation.4. The method of any of examples 1-3, further comprising delivering drugs to cells affected by the generated electric field, wherein the electroporation therapy increases a threshold molecule size of a drug that can be delivered to the cells.5. The method of any of examples 1-4, further comprising depleting a local supply of cells in the target treatment area responsible for initiating an inflammatory' response.6. The method of any of examples 1-5 wherein the method further comprises controlling the generated electric field to target fibroblast cells during a proliferation stage of a bleb healing process.7. The method of any of examples 1-6 wherein generating the electric field via the electrode assembly comprises applying a voltage value between about 3.5 V and about 7 V to the electrode assembly, and wherein the target treatment area comprises a subconjunctival bleb.8. The method of any of examples 1-7 wherein the electroporation assembly further comprises a delivery needle, and wherein delivering the electroporation assembly comprises: piercing a membrane of the target treatment area via the delivery needle; and delivering the electrode assembly through the delivery needle such that the electrode assembly assumes a predetermined shape at the target treatment area.9. The method of example 8, further comprising: retracting the electrode assembly through the delivery needle after generating the electric field; and removing the delivery needle from the patient.10. The method of any of examples 1-9 wherein delivering the electroporation assembly comprises: piercing a membrane of the target treatment area with a guide wire; extending the guide wire into the target treatment area such that the guide wire retains a predetermined shape at the target treatment area; and translating the electrode assembly along the guide wire to the target treatment area such that the electrode assembly retains the predetermined shape at the target treatment area.11. The method of any of examples 1-10 wherein: the electroporation assembly further comprises: a chip including a first end portion and a second end portion opposite the first end portion, wherein the electrode assembly is disposed at the first end portion; and a plurality of electrode contacts disposed at the second end portion, delivering the electroporation assembly comprises positioning the electrode assembly on or near a surface of the target treatment area; andgenerating the electric field comprises delivering electrical energy' to individual ones of the electrode contacts.12. An electroporation assembly, comprising: an electrode assembly including a first electrode and a second electrode spaced apart from the first electrode, wherein the electrode assembly is configured to generate an electric field; and an electrode delivery device coupled to the electrode assembly, wherein the electrode delivery device is configured to deliver the electrode assembly to a bleb target area on an eye, wherein the electrode assembly is transitionable between a linear delivery configuration and a spiraled shaped deployed configuration.13. The electroporation assembly of example 12 wherein the first and second electrodes are spaced apart by a distance between 50 pm and 250 pm.14. The electroporation assembly of example 12 or example 13 wherein the electrode assembly further includes an insulating material positioned between the first and second electrodes.15. The electroporation assembly of any of examples 12-14 wherein the electrode delivery device includes a delivery’ needle, and wherein the electrode assembly is configured to extend from and retract into the delivery needle.16. The electroporation assembly of any of examples 12-15 wherein the electrode assembly further includes an elongated moveable electrode component, and wherein the first electrode and the second electrode are positioned proximate a distal end of the elongated moveable electrode component.17. The electroporation assembly of example 16 wherein the elongated moveable electrode component includes a lumen extending therethrough, wherein the electrode delivery device comprises a guide wire configured to extend through the lumen, and wherein the elongated moveable electrode component is configured to be translated along the guide wire.18. The electroporation assembly of any of examples 12-17 wherein the first and second electrodes are spaced apart by a distance between 50 pm and 250 pm.19. An electroporation assembly, comprising: a chip having a first end portion and a second end portion opposite the first end portion; a plurality of surface electrodes coupled to the first end portion of the chip; and a plurality of electrode contacts coupled to the second end portion of the chip, wherein individual ones of the electrode contacts are electrically coupled to one or more individual ones of the surface electrodes.20. The electroporation assembly of example 19 wherein the plurality of surface electrodes comprises a plurality of annular surface electrodes concentric with one another.21. The electroporation assembly of example 19 wherein the plurality of surface electrodes comprises a plurality of surface electrodes interleaved with one another.22. The electroporation assembly of example 19 wherein: the plurality of surface electrodes comprises a first plurality of spot surface electrodes and a second plurality of spot surface electrodes arranged in rows and columns, wherein the first plurality of spot surface electrodes is electrically coupled to a first one of the electrode contacts, wherein the second plurality of spot surface electrodes is electrically coupled to a second one of the electrode contacts, wherein individual ones of the first plurality of spot surface electrodes and individual ones of the second plurality of spot surface electrodes alternate across individual ones of the rows and columns.23. The electroporation assembly of any of examples 19-22 wherein a number of the electrode contacts is equal to a number of the surface electrodes, and wherein individual electrode contacts are electrically coupled to corresponding individual surface electrodes.24. The electroporation assembly of any of examples 19-22 wherein a number of the electrode contacts is equal to a number of the surface electrodes, and wherein at least one of the electrode contacts is electrically coupled to more than one of the surface electrodes.25. The electroporation assembly of any of examples 19-22 wherein the plurality of electrode contacts comprises a first electrode contact and a second electrode contact, wherein the first electrode contact is electrically coupled to a first half of the surface electrodes, and wherein the second electrode contact is electrically coupled to a second half of the surface electrodes.26. The electroporation assembly of any of examples 19-22 wherein the first end portion of the chip includes a through hole.Conclusion

[0050] The above detailed descriptions of embodiments of the technology are not intended to be exhaustive or to limit the technology to the precise form disclosed above. Although specific embodiments of, and examples for, the technology are described above for illustrative purposes, various equivalent modifications are possible within the scope of the technology, as those skilled in the relevant art will recognize. While steps are presented in a given order, alternative embodiments may perform steps in a different order. Moreover, the various embodiments described herein may also be combined to provide further embodiments. Reference herein to "one embodiment," "an embodiment," or similar formulations means that a particular feature, structure, operation, or characteristic described in connection with the embodiment can be included in at least one embodiment of the present technology. Thus, the appearances of such phrases or formulations herein are not necessarily all referring to the same embodiment.

[0051] For ease of reference, identical reference numbers are used to identify similar or analogous components or features throughout this disclosure, but the use of the same reference number does not imply that the features should be construed to be identical. Indeed, in many examples described herein, identically numbered features have a plurality of embodiments that are distinct in structure and / or function from each other. Furthermore, the same shading may be used to indicate materials in cross section that can be compositionally similar, but the use of the same shading does not imply that the materials should be construed to be identical unless specifically noted herein.

[0052] Moreover, unless the word "or" is expressly limited to mean only a single item exclusive from the other items in reference to a list of two or more items, then the use of "or" in such a list is to be interpreted as including (a) any single item in the list, (b) all of the items in the list, or (c) any combination of the items in the list. Where the context permits, singular orplural terms may also include the plural or singular term, respectively. Additionally, the term "comprising" is used throughout to mean including at least the recited feature(s) such that any greater number of the same feature and / or additional types of other features are not precluded. Direct onal terms, such as "upper," "lower," "front," "back," "vertical," and "horizontal," may be used herein to express and clarify the relationship between various elements. It should be understood that such terms do not denote absolute orientation. Further, while advantages associated with certain embodiments of the technology have been described in the context of those embodiments, other embodiments may also exhibit such advantages, and not all embodiments need necessarily exhibit such advantages to fall within the scope of the technology'. Accordingly, the disclosure and associated technology can encompass other embodiments not expressly shown or described herein.

Claims

CLAIMSI / We claim:

1. A method for maintaining a bleb within an eye of a patient in the treatment of glaucoma, the method comprising: delivering an electroporation assembly to a target treatment area in a bleb within an eye of the patient, wherein the electroporation assembly comprises an electrode assembly; and generating an electric field via the electrode assembly to induce electroporation in at least a portion of the target treatment area, thereby minimizing the development of fibrosis and / or reducing generation of scar tissue in the target treatment area.

2. The method of claim 1 wherein the generated electric field has an electric field gradient less than about 500 V / cm, and wherein the electroporation therapy comprises reversible electroporation.

3. The method of claim 1 wherein the generated electric field has an electric field gradient greater than about 500 V / cm, and wherein the electroporation therapy comprises irreversible electroporation.

4. The method of claim 1, further comprising delivering drugs to cells affected by the generated electnc field, wherein the electroporation therapy increases a threshold molecule size of a drug that can be delivered to the cells.

5. The method of claim 1 , further comprising depleting a local supply of cells in the target treatment area responsible for initiating an inflammatory response.

6. The method of claim 1 wherein the method further comprises controlling the generated electric field to target fibroblast cells during a proliferation stage of a bleb healing process.

7. The method of claim 1 wherein generating the electric field via the electrode assembly comprises applying a voltage value between about 3.5 V and about 7 V to the electrode assembly, and wherein the target treatment area comprises a subconjunctival bleb.

8. The method of claim 1 wherein the electroporation assembly further comprises a delivery needle, and wherein delivering the electroporation assembly comprises: piercing a membrane of the target treatment area via the delivery needle; and delivering the electrode assembly through the delivery needle such that the electrode assembly assumes a predetermined shape at the target treatment area.

9. The method of claim 8, further comprising: retracting the electrode assembly through the delivery needle after generating the electric field; and removing the delivery needle from the patient.

10. The method of claim 1 wherein delivering the electroporation assembly comprises: piercing a membrane of the target treatment area with a guide wire; extending the guide wire into the target treatment area such that the guide wire retains a predetermined shape at the target treatment area; and translating the electrode assembly along the guide wire to the target treatment area such that the electrode assembly retains the predetermined shape at the target treatment area.

11. The method of claim 1 wherein: the electroporation assembly further comprises: a chip including a first end portion and a second end portion opposite the first end portion, wherein the electrode assembly is disposed at the first end portion; and a plurality of electrode contacts disposed at the second end portion, delivering the electroporation assembly comprises positioning the electrode assembly on or near a surface of the target treatment area; andgenerating the electric field comprises delivering electrical energy' to individual ones of the electrode contacts.

12. An electroporation assembly, comprising: an electrode assembly including a first electrode and a second electrode spaced apart from the first electrode, wherein the electrode assembly is configured to generate an electric field; and an electrode delivery device coupled to the electrode assembly, wherein the electrode delivery device is configured to deliver the electrode assembly to a bleb target area on an eye, wherein the electrode assembly is transitionable between a linear delivery configuration and a spiraled shaped deployed configuration.

13. The electroporation assembly of claim 12 wherein the first and second electrodes are spaced apart by a distance between 50 pm and 250 pm.

14. The electroporation assembly of claim 12 wherein the electrode assembly further includes an insulating material positioned between the first and second electrodes.

15. The electroporation assembly of claim 12 wherein the electrode delivery device includes a delivery needle, and wherein the electrode assembly is configured to extend from and retract into the delivery’ needle.

16. The electroporation assembly of claim 12 wherein the electrode assembly further includes an elongated moveable electrode component, and wherein the first electrode and the second electrode are positioned proximate a distal end of the elongated moveable electrode component.

17. The electroporation assembly of claim 16 wherein the elongated moveable electrode component includes a lumen extending therethrough, wherein the electrode delivery device comprises a guide wire configured to extend through the lumen, and wherein the elongated moveable electrode component is configured to be translated along the guide wire.

18. The electroporation assembly of claim 12 wherein the first and second electrodes are spaced apart by a distance between 50 pm and 250 pm.

19. An electroporation assembly, comprising: a chip having a first end portion and a second end portion opposite the first end portion; a plurality of surface electrodes coupled to the first end portion of the chip; and a plurality of electrode contacts coupled to the second end portion of the chip, wherein individual ones of the electrode contacts are electrically coupled to one or more individual ones of the surface electrodes.

20. The electroporation assembly of claim 19 wherein the plurality of surface electrodes comprises a plurality of annular surface electrodes concentric with one another.

21. The electroporation assembly of claim 19 wherein the plurality of surface electrodes comprises a plurality of surface electrodes interleaved with one another.

22. The electroporation assembly of claim 19 wherein: the plurality of surface electrodes comprises a first plurality of spot surface electrodes and a second plurality of spot surface electrodes arranged in rows and columns, wherein the first plurality of spot surface electrodes is electrically coupled to a first one of the electrode contacts, wherein the second plurality of spot surface electrodes is electrically coupled to a second one of the electrode contacts, wherein individual ones of the first plurality of spot surface electrodes and individual ones of the second plurality of spot surface electrodes alternate across individual ones of the rows and columns.

23. The electroporation assembly of claim 19 wherein a number of the electrode contacts is equal to a number of the surface electrodes, and wherein individual electrode contacts are electrically coupled to corresponding individual surface electrodes.

24. The electroporation assembly of claim 19 wherein a number of the electrode contacts is equal to a number of the surface electrodes, and wherein at least one of the electrode contacts is electrically coupled to more than one of the surface electrodes.

25. The electroporation assembly of claim 19 wherein the plurality of electrode contacts comprises a first electrode contact and a second electrode contact, wherein the first electrode contact is electrically coupled to a first half of the surface electrodes, and wherein the second electrode contact is electrically coupled to a second half of the surface electrodes.

26. The electroporation assembly of claim 19 wherein the first end portion of the chip includes a through hole.

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