Electrode arrays for electroporation, and related systems and methods

Abstract

Providing an electrode array for electroporation, as well as related systems and methods. [Solution] An electrode array for use with an electroporation device includes a support member having an upper surface and a bottom surface, defining a plurality of injection channels extending from the upper surface to the bottom surface. The plurality of needle electrodes are coupled to the support member such that the distal ends of the plurality of needle electrodes extend to a needle depth below the bottom surface. The plurality of needle electrodes are arranged in a matrix pattern having rows and columns of needle electrodes arranged along the support member. The plurality of injection channels are dispersed within the matrix pattern.

Description

Technical Field

[0001] Cross - reference to Related Applications This application claims the benefit of U.S. Provisional Patent Application No. 63 / 217,083, filed Jun. 30, 2021, the entire content of which is incorporated herein by reference.

[0002] The present invention relates to an electroporation device, and more particularly, to an electrode array adapted to provide an increased injection volume and a more voluminous electroporation field within a tissue.

Background Art

[0003] Conventional modes of administering vaccines and other pharmaceuticals into body tissue are by direct injection into muscle or skin tissue using a syringe and needle. To facilitate direct delivery of such a vaccine or drug into the cells within the tissue, it is known to incorporate an electroporation pulse of electrical energy at or near the injection site. Such direct delivery to cells using an electroporation electrical pulse can have a greater clinical effect on the quality of the body's metabolic and / or immune system responses than a simple syringe and needle injection. Moreover, the ability to directly deliver a drug intracellularly via electroporation enables the effective delivery of any number of therapeutic agents, including antigens for inducing an immune response, or alternatively, metabolites for affecting various biological pathways that result in a clinical effect (e.g., DNA - encoded monoclonal antibodies (dMAb), expressible naked DNA encoding a polypeptide, expressible naked DNA encoding a protein, recombinant nucleic acid sequences encoding an antibody, etc.).

Summary of the Invention

[0004] According to one embodiment of the present disclosure, an electrode array for use with an electroporation device includes a support member having an upper surface and a bottom surface, defining a plurality of injection channels extending from the upper surface to the bottom surface. The plurality of needle electrodes are coupled to the support member such that the distal ends of the plurality of needle electrodes extend to a needle depth below the bottom surface. The plurality of needle electrodes are arranged in a matrix pattern having rows and columns of needle electrodes arranged along the support member. The plurality of injection channels are dispersed within the matrix pattern.

[0005] According to another embodiment of the present disclosure, an electroporation device for inducing reversible electroporation in tissue cells comprises an electrode array and a plurality of injection needles. The electrode array includes a support member having an upper surface and a bottom surface and defining a plurality of injection channels extending from the upper surface to the bottom surface. The plurality of needle electrodes are coupled to the support member such that the distal ends of the plurality of needle electrodes extend to a needle depth below the bottom surface of the support member. The plurality of needle electrodes are arranged in a matrix pattern having rows and columns of needle electrodes arranged along the support member. The plurality of injection channels are dispersed within the matrix pattern. The injection needles are configured to extend into tissue through at least some of the plurality of injection channels.

[0006] According to another embodiment of the present disclosure, an electroporation system for inducing reversible electroporation in tissue cells includes an electrode array having a support member having an upper surface and a bottom surface and defining a plurality of channels extending from the upper surface to the bottom surface. The plurality of needle electrodes are coupled to the support member and extend through the plurality of channels such that the distal ends of the plurality of needle electrodes extend to a needle depth below the bottom surface of the support member. The plurality of needle electrodes are arranged in a matrix pattern having rows and columns of needle electrodes arranged along the support member. At least some of the plurality of needle electrodes are dual-purpose needle electrodes configured to deliver one or more electroporation pulses to the tissue in order to inject a drug into the tissue and induce reversible electroporation within the tissue cells.

[0007] The above summary and the following detailed description of exemplary embodiments of this application will be better understood when read in conjunction with the accompanying drawings. For the purpose of illustrating the features of this application, exemplary embodiments are shown in the drawings. However, it should be understood that this application is not limited to the exact arrangements and fixtures shown. These are the drawings below. [Brief explanation of the drawing]

[0008] [Figure 1A] This is a side plan view of an electroporation system having a handheld electroporation device incorporating an electrode array, according to one embodiment of the present disclosure. [Figure 1B] Figure 1A is a cross-sectional side view of the mounting portion of a handheld electroporation device that supports the electrode array shown. [Figure 1C] Figure 1B is a top view of an electrode array shown in one embodiment of the present disclosure, which has an electrode array having injection channels for receiving electropermeable needles and injection needles scattered between the electropermeable needles arranged in an exemplary 5x2 matrix. [Figure 1D] Figure 1C is a side view of the electroporation needle array shown. [Figure 2A] This is a perspective view of an array according to one embodiment of the present disclosure, having an exemplary 6x4 matrix arranged with injection channels for receiving electropermeable needles and injection needles scattered between the electropermeable needles. [Figure 2B] Figure 2A is a side view of the array shown. [Figure 2C] Figure 2A is a bottom view of the array shown. [Figure 2D] Figure 2A is a top view of the array shown. [Figure 3A] This is a bottom view of an array similar to the arrays shown in Figures 2A to 2D, but with different inter-electrode spacings, according to one embodiment of the present disclosure. [Figure 3B] Figure 3A is a top view of the array shown. [Figure 3C]Figure 3A is a bottom view illustrating the calculated magnitude of the electric field of the array shown. [Figure 4] This is a bottom view of a modular array according to one embodiment of the present disclosure, having an exemplary 6x4 matrix arrangement of electropermeable needles and injection channels for receiving injection needles scattered between the electropermeable needles. [Figure 5A] This is a perspective view of an electroporation system comprising an array having dual-purpose injection and electroporation needles arranged in a matrix according to one embodiment of the present disclosure, wherein the needle electrodes are dual-purpose injection needles configured to both deliver an injection solution to a target tissue and deliver one or more electroporation pulses to the target tissue. [Figure 5B] Figure 5A is a perspective view of the array assembly of the electroporation system shown. [Figure 5C] This is a plan view illustrating an array assembly inserted into muscle tissue. [Figure 6A] This is a bottom view of an electroporation array assembly according to one embodiment of the present disclosure, having electroporation needles arranged in a 3x2 matrix and injection channels eccentrically offset from the electroporation needles. [Figure 6B] Figure 6A is a side view of the electroporation array assembly shown. [Figure 7A] This is a bottom view of an electroporation array assembly according to one embodiment of the present disclosure, having electroporation needles arranged in a 3x2 matrix and injection channels aligned with the rows of electroporation needles. [Figure 7B] Figure 7A is a side view of the electroporation array assembly shown. [Figure 8A] Figures 7A and 7B illustrate exemplary pulse patterns of the electrode array shown. [Figure 8B] Figures 7A and 7B illustrate exemplary pulse patterns of the electrode array shown. [Figure 8C] Figures 7A and 7B illustrate exemplary pulse patterns of the electrode array shown. [Figure 9A]A plan view showing the electroporation array assembly of FIG. 7A inserted into muscle tissue in an orientation parallel to muscle fibers. [Figure 9B] A plan view showing the electroporation array assembly of FIG. 7A inserted into muscle tissue in an orientation perpendicular to muscle fibers. [Figure 9C] A series of diagrams illustrating the magnitudes of the calculated electric fields in various orientations of the electrode rows of the array shown in FIGS. 7A - 7B with respect to muscle fibers.

Mode for Carrying Out the Invention

[0009] The present disclosure can be more readily understood by reference to the following detailed description, which is presented in connection with the accompanying figures and examples that form a part of the present disclosure. It is to be understood that the present disclosure is not limited to the specific devices, methods, uses, conditions or parameters described and / or shown herein, and that the terms used herein are for the purpose of describing particular embodiments by way of example and are not intended to limit the scope of the present disclosure. Also, as used herein, including the appended claims, the singular forms “a,” “an,” and “the” include the plural, and references to a particular numerical value include at least that particular value unless the context clearly indicates otherwise.

[0010] As used herein, the term “plurality” means more than one. When ranges of values are expressed, other embodiments include from a certain particular value and / or to other certain particular values. Similarly, when values are expressed as approximations, it will be understood by use of the antecedent “about” that a particular value forms another embodiment. All ranges are inclusive and combinable.

[0011] As used herein, the terms "about", "approximately", and "substantially" with respect to dimensions, angles, ratios, and other geometric shapes take into account manufacturing tolerances. Further, the terms "about", "approximately", and "substantially" may include those that are 10% greater or less than the recited dimensions, ratios, or angles. Further, the terms "about", "approximately", and "substantially" can be equally applied to the recited specific values.

[0012] As used herein, the term "agent" means a polypeptide, polynucleotide, small molecule, or any combination thereof. The agent may be a recombinant nucleic acid sequence encoding an antibody, a fragment thereof, a variant thereof, or any combination thereof. The agent may be a recombinant nucleic acid sequence encoding a polypeptide or protein. The agent may be formulated, by way of non-limiting example, in a buffer such as water or saline-sodium citrate (SSC) or phosphate buffered saline (PBS).

[0013] As used herein, the term "intradermal" means within the layers of the skin, including the epidermis (i.e., the epidermal layer from the stratum corneum to the basal layer) and the dermis (i.e., the dermal layer).

[0014] As used herein, the term "intramuscular" means within muscle tissue, including skeletal muscle tissue and smooth muscle tissue.

[0015] As used herein, the term "adipose" means a layer containing adipocytes (i.e., fat cells) present in the subcutaneous layer.

[0016] As used herein, the term "electroporation" means utilizing an electric field within a tissue that temporarily and reversibly increases the permeability and / or porosity of the cell membranes of cells within the tissue, thereby enabling, for example, an agent to be introduced into the cells. It should be recognized that the types of electroporation disclosed herein refer to reversible electroporation (also referred to as "reversible poration"), which means that the electroporated cell membranes (or at least a majority thereof) return to a substantially impermeable and / or non-porous state after electroporation.

[0017] As used herein, the term “electroporation field” means an electric field capable of electroporating cells. In examples where an electric field includes a portion capable of electroporating cells and another portion that is not, “electroporation field” specifically refers to the portion of the electric field capable of electroporating cells. Thus, an electroporation field can be a subset of an electric field.

[0018] Embodiments disclosed herein relate to electroporation devices using electrode arrays having multiple needle electrodes arranged in a pattern and multiple fluid injection channels scattered within the pattern. Arrays with multiple fluid injection channels allow for greater injection volume due to increased spatial dispersion within a larger volume electroporation field in target tissue. This can enable drug uptake into target cells on a larger scale, including within intradermal (ID) tissue, adipose tissue, and intramuscular (IM) tissue.

[0019] Referring to Figures 1A and 1B, an electroporation system 2 according to an exemplary embodiment of the present disclosure includes a handheld electroporation device 4 including a housing 6. The handheld electroporation device 4 may also be referred to as the “applicator” 4. The electroporation device 4 includes a handle 8 and a mounting portion 10 (also referred to herein as the “mounting head” or “applicator head” 10) extending distally from the handle 8. The handle 8 and the applicator head 10 may be defined by the housing 6. The applicator head 10 can carry an array assembly 212 including one or more electrodes 14, such as a plurality of electrodes 14 in a spatial arrangement, which may be referred to as the “electrode array” 215. The electrodes 14 extend from a support member 216 in a distal direction D opposite to the proximal direction P. The electrodes 14 in this embodiment are penetrating electrodes having a distal tip 18 configured to penetrate tissue in order to penetrate into muscle tissue, in particular through skin tissue. One or more, and at most all, of the distal tips 18 may be trocar tips having a planar surface converging to a point at the distal end 19 of the electrode 14, as an example without limitation.

[0020] Specifically, the electrode 14 is configured to deliver one or more pulses of electrical energy to cells in a target tissue in order to reversibly electroperforate the cells. The device 4 includes a circuit for providing electrical communication between the electrode 14 and the energy source 110. As shown in the figure, the circuit may be configured to connect to one or more cables 109 configured to couple with the energy source 110, which is located away from the handheld electroperforation device 4, such as a generator. Additionally or alternatively, the circuit may be configured to connect to an onboard energy source, such as a battery unit disposed within the housing 6.

[0021] The energy source 110 can be electrically connected to a pulse generator 112, such as a waveform generator, for generating electrical signals in the form of one or more electrical pulses having specific electrical parameters for electroperforating cells in tissue and transmitting them to the electrode 14. Such electrical parameters include potential (voltage), current type (alternating current (AC) or direct current (DC)), current magnitude (amperes), pulse duration, pulse quantity (i.e., the number of pulses delivered), and time interval or "delay" between pulses (in the case of multiple pulse delivery). The pulse generator 112 may include a waveform logger for recording the electrical parameters of the delivered pulse(s). The pulse generator 112 can be electrically connected to a control unit 114 (also referred to herein as the "controller"), which may include a processor 116 configured to control the operation of the electroperforation system 2, including the operation of the pulse generator 112. The processor 116 can be electronically connected to computer memory 118 and may be configured to run software and / or firmware containing one or more algorithms for controlling the operation of the system 2.

[0022] The processor 116 can electrically communicate with a user interface that may be located on or off the device 4. The user interface may include a display for presenting information related to the operation of system 2 and an input unit such as a keypad or touchscreen that allows a physician to input information such as commands related to the operation of system 2. It should be recognized that the interface may be a computer interface such as a tabletop computer or laptop computer, or a handheld electronic device such as a smartphone.

[0023] The applicator head 10 is configured to receive at least one fluid delivery device, which includes an elongated tubular member, the elongated tubular member being, in the embodiments disclosed herein, an injection needle 20 configured to deliver an injection to a target area of ​​tissue. Preferably, the applicator head 10 is configured to receive a plurality of fluid delivery devices (e.g., injection needles 20), as described in more detail below.

[0024] As shown in Figure 1B, the handheld electroporation device 4 may include one or more mounting members 26 for attaching the support member 216 to the applicator head 10. The mounting members 26 can define each opening into which a portion of the electrode 14 extends. The support member 216 may include a hub or platform 32 into which a plurality of electrode openings 34 into which the electrode 14 can each extend can define the pattern of the electrode array 215. The support member 216 defines a plurality of injection channels 236 into which the injection needle 20 can extend. The support member 216 also preferably includes a plurality of elongated proximal tubular structures 238 (also referred to herein as “chimneys” or “risers”) extending from the upper surface 262 of the platform 32. The chimneys 238 define the proximal extensions of the injection channels 36 from the platform 32. The platform 32 may be configured to contact one or more of the mounting members 26 when the array assembly 212 is assembled and coupled to the applicator head 10.

[0025] It should be recognized that at least one mounting member 26 can define a plurality of sockets 44 positioned in correspondence with the electrode opening 34 of the support member 216 in order to receive the proximal end 17 of the electrode 14 and provide electrical communication between the pulse generator 112 and the electrode 14. In addition, one or more of the mounting members 26 can also align with the injection channel 236 of the support member 216 and define a respective injection channel 48 into which a chimney 238 may extend.

[0026] As illustrated, the chimney 238 can protrude proximally from the applicator head 10 when in an assembled configuration. The proximal end 56 of the chimney 238 may be configured to be attached to a connecting member 58 (also referred to herein as the “connector”) which is attached to the injection needle 20. The connector 58 is configured to connect to a reservoir of an injection solution, such as a syringe, single-dose cartridge, or injection manifold. As illustrated, the connector 58 may be a Luer connector, but other types and designs of connectors are also within the scope of this embodiment.

[0027] In some embodiments, the electroporation system 2 may employ a CELLECTRA® 2000 system having an external battery-powered pulse generator 112 (i.e., a CELLECTRA® pulse generator) connected via a cable to a handheld electroporation device 4, which may be a modified version of the CELLECTRA® 5P-IM applicator, as a non-limiting example. It should be noted that the array assembly 212 is preferably a sterile, disposable array assembly 212. The electrodes 14 may be made of stainless steel and may be coated with gold to enhance conductivity. The injection needles 20 may be pre-packaged with the array assembly 212. It should be noted that the CELLECTRA® products and components described above are manufactured by Inovio Pharmaceuticals, Inc., headquartered in Plymouth Meeting, Pennsylvania, USA.

[0028] As illustrated in Figure 1B, the array assembly 212 is preferably configured to control the maximum depth L1 to which the electrode 14 penetrates the surface of the target skin. This depth L1, also referred herein as “electrode penetration depth” or “electrode depth,” can be regulated by a contact or “stop” surface 260 of the array assembly 212, which is configured to contact the target skin and stop the electrode 14 from advancing further into the tissue. As illustrated, the stop surface 260 may be defined, in non-limiting examples, by the distal or bottom surface of the support member 216. The array assembly 212 is also preferably configured to control the maximum depth L2 of the injection needle 20, measured from the stop surface 260 to the distal end of the injection needle 20. This depth L2 may also be referred herein as “injection depth.” The support member 216 is preferably configured such that the injection depth L2 is shallower than the electrode depth L1 by an injection offset distance L3, which is adjusted so that the injected drug is located primarily within the electroporation field created by the electrode 14. It should be recognized that depths L1 and L2 may be adjusted as needed to specifically target intradermal (ID) tissue, adipose tissue, intramuscular (IM) tissue, or any combination of the aforementioned tissues, depending on the patient's needs.

[0029] Referring here to Figures 1C to 1D, an exemplary support member 216 can carry needle electrodes 14 such that the electrode array 215 is a grid or “matrix” pattern. The embodiment shown uses a matrix having five rows 217 and two columns 219 of electrodes 14 (i.e., a 5 × 2 electrode array 215 having two electrodes in each row and five electrodes in each column). The rows 217 are spaced apart along the longitudinal direction X1, while the columns 219 are spaced apart along the transverse direction Y1 which is substantially perpendicular to the longitudinal direction X1. In this way, the array 215 can be elongated along the longitudinal direction X1. It should be noted that the electrodes 14 in each row 217 can be aligned along a row axis 247 which may intersect with the central axis 245 of the electrodes 14 in the row 217. Additionally, the electrodes 14 in each column 219 can be aligned along a column axis 249 which may intersect with the central axis 245 of the electrodes 14 in the column 219. The array 215 may use equidistant row and column spacings X2, Y2, although in other embodiments, the row spacing X2 may differ from the column spacing Y2. The row and column spacings X2, Y2 are preferably measured between adjacent row axes 247 and column axes 249, respectively. The electrodes 14 may be configured similarly to those described above for the circular pattern electrode array 15, although in other embodiments, the electrodes 14 of the array 215 may be adapted as needed.

[0030] The support member 216 has first and second ends 202, 204 facing each other along the longitudinal direction X1, and opposing first and second sides 206, 208 facing each other along the transverse direction Y1. The bottom surface 260 of the support member can effectively define the stop surface as described above. As shown in the figure, the support member 216 may include three injection channels 236 which may be aligned with each other along the longitudinal direction X1 and be equidistant between first and second rows 219. The first injection channel 236 may also be positioned equidistant between first and second rows 217, the second injection channel 236 may be aligned laterally within a third row 217, and the third injection channel 236 may be positioned equidistant between fifth and sixth rows 217. Each chimney 238 may be configured to receive its respective injection needle 20, which may be configured according to any of the embodiments described above. As shown in Figure 1C, the chimney 238 may extend proximal to the upper surface 262 of the support member 216 along the vertical direction Z1 to a chimney height L4, and the height L4 may be configured to position the distal end of the injection needle 20 in a preferred position relative to the distal end 19 of the electrode 14, such as the preferred injection offset distance L3 described above.

[0031] As illustrated in Figure 1D, the injection needles 20 can each discharge their respective injection fluids, which can be dispersed radially outward toward adjacent needle electrodes 14. By using multiple injection channels 236, the array 215 can be configured to disperse a larger volume of injection fluid into a larger electroporation field. According to one example of this embodiment, the array 215 can be configured to deliver a total injection volume of about 3 mL from the injection needles 20, in particular 1 mL per injection needle 20. When used for intramuscular (IM) electroporation, it should be recognized that the elongated array 215 allows the physician to orient the array 215 so that its longitudinal direction X1 is roughly aligned with the direction of muscle fiber stretching, thereby further enhancing fluid dispersion within the patient's muscle tissue.

[0032] Referring here to Figures 2A to 2D, another exemplary array assembly 312 includes a support member 316 having an array 315 of needle electrodes 14 arranged in a matrix having six rows 317 and four columns 319 (i.e., a 6×4 matrix electrode array 315). As described above, the rows 317 are spaced apart along the longitudinal direction X1, while the columns 319 are spaced apart along the transverse direction Y1, so that the array 315 may be elongated along the longitudinal direction X1. The array 315 can use equidistant row and column spacings. As a non-limiting example, the rows 317 can be spaced apart from each other at a distance of about 10 mm X2, and the columns 319 can be spaced apart from each other at a distance of about 10 mm Y2. It should be recognized that such a 10 mm spacing approximates the diameter of the circular electrode array of the CELLECTRA® 5P-IM array, as illustrated in Figure 2C for reference.

[0033] In other embodiments, as shown in Figures 3A and 3B, the row spacing can differ from the column spacing. In this example, the columns can be spaced about 10 mm apart (X2), and the rows can be spaced about 7.5 mm apart (Y2). Additional spacing distances are described below.

[0034] The support member 316 of the array 315 illustrated in Figures 2A and 2B preferably includes a plurality of injection channels 336 which may be defined within a vertically elongated chimney 338. As shown, the plurality of injection channels 336 may include six injection channels 336 which may be arranged along two rows 340 of channels, such as a first row 340 of channels 336 equidistant between the second and third rows 319 of electrodes 14, and a second row 340 of channels 336 equidistant between the fourth and fifth rows 319 of electrodes 14. As shown in Figure 2D, the channel rows 340 may be spaced apart from each other by a spacing distance X3, measured between each channel row axis 351 intersecting the central axis 355 of the injection channels 336 within the channel row 340. In the shown embodiment, the spacing distance X3 is twice the electrode row spacing distance X2. Channel 336 may also be arranged in rows 342 of channel 336, such as the first, second, and third rows 342 of channel 336. The channel rows 342 may be spaced apart from each other by a spacing distance Y3, measured between the respective channel row axes 353 that intersect with the central axis 355 of the injection channels 336 within the channel row 342. In the shown embodiment, the spacing distance Y3 is equivalent to the spacing distance of the electrode row 319.

[0035] According to one example of this embodiment, the array 315 may be configured to deliver a total injection volume of approximately 6 mL from the injection needle 20, in particular at 1 mL per injection needle 20. It should be recognized that the array 315 may be used to deliver injection volumes greater than and less than 6 mL. Similar to the array 215 described above, the array 315 may be preferably oriented with respect to the direction of muscle fiber stretching, thereby enhancing fluid dispersion within the muscle tissue. Additionally, the chimney 338 has a height L4 which may be configured to position the injection area of ​​the injection needle 20 in a preferred position relative to the distal end 19 of the electrode 14. It should be recognized that the electrode and channel spacing distances X2, Y2, X3, Y3, electrode depth L1, and / or chimney height L4 of the matrix arrays 215, 315 described above can be varied as needed. For example, the spacing distances X2, Y2, X3, and Y3 may be in the range of approximately 2.5 mm to approximately 50 mm, more specifically in the range of approximately 4.0 mm to approximately 20 mm, and more specifically in the range of approximately 5.0 mm to approximately 15.0 mm. The electrode spacing distances X2 and Y2 along the direction of muscle fiber extension are preferably in the range of approximately 10.0 mm to approximately 15.0 mm. The electrode spacing distances X2 and Y2 along the direction perpendicular to the direction of muscle fiber extension are preferably in the range of approximately 5.0 mm to approximately 10.0 mm. It should be recognized that the aforementioned spacing distances can be particularly adapted to the anatomical structure of the target tissue, especially when the target tissue has anisotropic electrical and fluid properties.

[0036] Referring here to Figure 3C, a computer model shows an example of the electric field generated by the array 315 illustrated in Figures 3A and 3B. As illustrated, the electric field can have a substantially uniform magnitude, expressed in V / cm, along the longitudinal direction X1 between adjacent rows. In this way, the array 315 can provide both preferred longitudinal fluid dispersion and a preferred "smooth" electroporation field along the longitudinal direction X1. A physician can utilize such a smooth electroporation field by oriented the array 315 in a preferred manner with respect to the underlying target tissue. For example, when used in IM electroporation, a physician can orient the array 315 so that its longitudinal direction coincides with the direction of muscle fiber stretching.

[0037] In further embodiments, the matrix arrays 215, 315 may be further configured for selective or "modular" use of electrodes 14 and / or their injection channels 236, 336. Referring here to Figure 4, as a non-limiting example, an exemplary array 415 having electrodes 14 arranged in a matrix such as a 6×4 matrix with equal spacing X2, Y2 between electrode rows 417 and columns 419 may include a total of 15 chimneys 438 (and channels 436) arranged in rows 440 and column 442 of a 5×3 chimney array, configured such that each chimney 438 is equidistant between adjacent rows 419 and rows 417 of electrodes 14. The array 415 may include circuits for individually connecting each electrode 14 to a pulse generator 112 so that the pulse generator 112 can deliver electroporation pulses to any subset of electrodes 14. Similarly, any subset of chimneys 438 may be used to receive their respective injection needles 20. In this way, a single matrix array 438 can provide the functionality of multiple matrix arrays 438. For example, the described 6×4 matrix array can be selectively used as one of 1×1, 1×2, 1×3, 2×1, 2×2, 2×3, 3×1, 3×2, 3×3, 4×1, 4×2, 4×3, 5×1, 5×2, and 5×3 chimney arrays, and as one of 1×1, 1×2, 1×3, 1×4, 2×1, 2×2, 2×3, 2×4, 3×1, 3×2, 3×3, 3×4, 4×1, 4×2, 4×3, 4×4, 5×1, 5×2, 5×3, 5×4, 6×1, 6×2, 6×3, and 6×4 electrode arrays.

[0038] Referring here to Figures 5A to 5C, an example of an electroporation system 602 is illustrated, which includes an electrode array assembly 612 having a plurality of needle electrodes 625 arranged in rows 617 and columns 619 in a matrix array 615, similar in general to the embodiments described above. However, in this embodiment, one or more, and up to all, of the electrodes 625 in the matrix array 615 may be dual-purpose injection needle electrodes 625 configured to both inject fluid into target tissue and deliver one or more electroporation pulses to the target tissue.

[0039] The electroporation system 602 of this embodiment may include tubing 659 for delivering fluid injection to each dual-purpose needle electrode 625 in a matrix array 615. The tubing 659 can connect the proximal ends 657 of the dual-purpose needle electrodes 625 to reservoirs, for example, via a manifold of a reservoir assembly and / or via a plurality of individual reservoirs. The array assembly 612 may be configured to couple with the applicator head 610 of a handheld electroporation device 604. For example, the array assembly 612 may include a support member 616 configured to couple with one or more complementary mounting members of the applicator head 610, similar to the configuration described above with reference to Figure 1B. The dual-purpose electrodes 625 may extend through dual-purpose channels 636 defined through the support member 616. It should be recognized that the support member 616 may be used in a modular manner, similar to the configuration described above with reference to Figure 4. For example, the dual-purpose electrode 625 may be inserted into a selected subset of the available dual-purpose channels 636, which may be selected based on the required fluid delivery and electroporation field parameters, and which parameters (and thus subset selection) may be adapted to the target tissue. It should be recognized that the matrix array 615 can be used with various combinations and patterns of the needle electrode 14, the injection needle 20, and the dual-purpose injection needle electrode 625.

[0040] As illustrated in Figure 5C, the matrix array 615 can be positioned relative to muscle tissue 675 such that the dual-purpose injection needle electrodes 625 are oriented as desired relative to the muscle tissue, particularly in the direction of muscle fiber stretch M1. For example, the matrix array 615 may be oriented such that its longitudinal direction X1 extends along the direction of muscle fiber stretch M1, as indicated by the position of the array 615 illustrated by the dashed line. Alternatively, the physician may choose to orient the array 615 such that its longitudinal direction X1 is substantially perpendicular to the direction of muscle fiber stretch M1, which can therefore provide fluid injection distributed along more individual muscle fiber striae. Such selective orientation and use of the array 615 can be further adjusted by applying a pulse pattern with respect to a particular subset of dual-purpose electrodes, which can be adapted to focus the EP field along the direction of muscle fiber stretch M1. These configurations and uses can also take advantage of the fact that during the flow of EP current, impedance is reduced when it is oriented in the same direction as the muscle fibers. Furthermore, the direction of fluid discharge from the injection needles 20,625 can also be expected to experience less mechanical impedance to the fluid flow, which can enable the distribution of beneficial drugs along the electroporation field.

[0041] Referring here to Figures 6A–6B, an exemplary embodiment of the array assembly 712 is illustrated having a matrix electrode array 715 coupled to a support member 716. In this exemplary embodiment, the matrix array 715 includes a plurality of needle electrodes 14, having injection channels 736 arranged in rows 717 and columns 719 and positioned between the needle electrodes 14, similar in general to the embodiments described above with reference to Figures 1C–3B and 4–5C. However, in this embodiment, one or more, and at most all, of the injection channels 736 are eccentrically offset from adjacent rows 717 and / or adjacent columns 719. As used herein with respect to the injection channels 736 and adjacent rows 717 and / or adjacent columns 719, the term “eccentrically offset” means that the injection channels 736 are spaced apart from the nearest row 717 and / or column 719 by an offset distance smaller than the distance along each respective direction between the injection channel 736 and the next nearest row 717 and / or column 719.

[0042] In the shown embodiment, each of the injection channels 736 is eccentrically offset from its nearest row 717 along the longitudinal direction X1. In particular, each injection channel 736 in the shown embodiment is longitudinally spaced from the nearest row 717 by an offset distance X4 less than the secondary offset distance X5 between the injection channel 736 and the next nearest row 717. The offset distance X4 and the secondary offset distance X5 are measured between the central axis 755 of the injection channel 736 and the nearest electrode row axis 747 and the next nearest electrode row axis 747, respectively. The offset distance X4 can be quantified as a coefficient (i.e., a multiple) of the secondary offset distance X5. For example, the offset distance X4 may range from a coefficient of approximately 0.001 to a coefficient of approximately 0.999 of the secondary offset distance X5.

[0043] According to a non-limiting example of the embodiment shown, the matrix array 715 has six electrodes 14 arranged in a 3×2 matrix (i.e., three rows 717 and two columns 719) with equidistant row and column spacings X2, Y2. The injection channels 736 are arranged in a 3×1 channel array (i.e., three rows 740 and one column 742 of channels 136) such that each injection channel 736 is eccentrically offset from the nearest row 717 of the electrodes 14 by an equidistant offset distance X4. In this example, each offset distance X4 is a coefficient of approximately 0.25 of the respective secondary offset distance X5. In particular, in this example, the electrode row spacing X2, electrode column spacing Y2, and channel row spacing X3 are each approximately 10 mm, and the injection channels are eccentrically offset by an offset distance X4 of approximately 2.5 mm along the longitudinal direction X1. It should be recognized that any of these spacing distances X2, Y2, and offsets X4, X5 can be adjusted as needed.

[0044] Furthermore, it should be recognized that in other embodiments, the injection channel 736 may be eccentrically offset from one of the electrode rows 719 along the lateral direction Y1. It should also be further recognized that the number of electrodes 14 and / or injection channels 736 in the matrix array 715 may be reduced or increased as needed, based on various factors such as the target treatment location, target tissue, and injection volume, as a non-limiting example. For example, the matrix array 715 may be increased to include one or more additional rows 717 and / or columns 719 of electrodes 14, and one or more additional rows 740 and / or columns 742 of injection channels 736, such that the injection channels 736 are eccentrically offset from the electrode rows 717. Furthermore, it should be recognized that the matrix array 715 may utilize a combination of eccentrically offset injection channels 717 (e.g., by being positioned equally between each electrode 14 or aligned with each electrode row 717) and non-eccentrically offset injection channels 717. The matrix array 715 of this embodiment offers significant advantages for electroporation procedures. One such advantage is that by using multiple injection channels 736 within the electrode array 715, the drug dose can be fractionated across multiple injection sites. This is expected to enhance fluid dispersion within the target tissue.

[0045] Referring here to Figures 7A-7B, in another exemplary embodiment, the array assembly 812 has a support member 816 including a matrix array 815 configured similarly to the embodiments described above with reference to Figures 6A-6B. Similar to the embodiments described above, the matrix array 815 has six electrodes 14 arranged in a 3x2 matrix with equidistant electrode row and column spacings X2, Y2, and three injection channels 836 arranged in a 3x1 channel array. However, in this embodiment, the injection channels 836 are aligned with the rows 817 of electrodes 14 such that the injection channels 836 intersect by their respective electrode row axes 847. In one non-limiting example of the matrix array 815, the array 815 may use electrode row spacing X2, electrode column spacing Y2, and channel row spacing X3, each approximately 10 mm. It should be recognized that any of these spacing distances X2, Y2, and X3 can be adjusted as needed.

[0046] The matrix array 815 of this embodiment offers significant advantages for electroporation procedures. Similar to the matrix array described above, the array 815 utilizes multiple injection channels 836 that enable fractionation of drug dosages between multiple injection sites. Furthermore, the injection fluid dispersed at multiple injection sites can be targeted by respective electroporation fields delivered by each subset of electrodes 14 within the array 815. Another advantage is that the matrix array 815 can use pulse patterns that enhance the co-localization of the electroporation field with the delivered fluid dispersion from the injection channels 836 aligned with the electrode rows 817. In particular, the matrix array 815 can use pulse patterns that deliver pulses between the electrode pairs of each row 817, thereby directing the pulses across the area below the injection channels 836. This allows for better co-localization of the electroporation field with the fluid dispersion released from the injection needles 14 extending through the injection channels 836, as will be described in more detail below.

[0047] Referring here to Figure 8A, an exemplary pulse pattern is described for the matrix array 81 illustrated in Figures 7A and 7B. For the purpose of illustrating the pulse pattern, the electrodes 14 of the matrix array 815 are referred to by electrode positions E1 to E6, where electrode positions E1 and E2 are on the first electrode row 817, electrode positions E3 and E4 are on the second electrode row 817, and electrode positions E5 and E6 are on the third electrode row 817. In this example, the pulse pattern includes three pulses, of which the first pulse P1 is delivered between E1 and E2, the second pulse P2 is delivered between E3 and E4, and the third pulse P3 is delivered between E5 and E6. In another example, the pulse pattern illustrated in Figure 8A can be repeated to provide a pulse pattern having two identical pulse trains and a total of six pulses. Such a repeated pulse pattern provides two pulses per electrode pair, which can facilitate enhanced electroporation results.

[0048] Referring here to Figure 8B, in an additional example, the pulse pattern can use four additional pulses P4-P7 delivered diagonally between adjacent electrode rows 817 and column 819, in addition to the three pulses P1-P3 illustrated in Figure 8A. In this particular example, the fourth pulse P4 is delivered between E1 and E4, the fifth pulse P5 is delivered between E4 and E5, the sixth pulse P6 is delivered between E2 and E3, and the seventh pulse P7 is delivered between E3 and E6. The four diagonal pulses P4-P7 may be useful for colocalizing the electroporation field with any injection solution dispersed between the electrode rows 817 along the longitudinal direction X1.

[0049] Referring here to Figure 8C, in a further example for colocalizing the electroporation field with the injection fluid longitudinally dispersed between the electrode rows 817, the pulse pattern can effectively replace pulses P4-P7 illustrated in Figure 8B with two alternative pulses P4-P5 that diagonally divide the current from the central row 817 to the first and third rows 817, respectively. In particular, in this example, the fourth pulse P5 is delivered from E3 to both E2 and E6, and the fifth pulse P5 is delivered from E4 to both E1 and E5. This pulse pattern can effectively target the injection fluid dispersed between the electrode rows 817 using fewer total pulses than the pattern illustrated in Figure 8B.

[0050] Referring to Figures 8A to 8C, it should be recognized that the exemplary pulse patterns described above represent non-limiting examples of pulse patterns that can be used with the matrix array 815. It should also be recognized that the aforementioned pulse patterns can be used with the matrix array 715 illustrated in Figures 6A to 6B. Furthermore, these pulse patterns can be adjusted as needed based on the specific factors involved.

[0051] Referring here to Figures 9A-9C, an additional advantage of the matrix array 815 described above, with reference to Figures 7A-7B, is its particular effectiveness in tissues that affect fluid dispersion along a specific direction. One such tissue is muscle tissue 675. As mentioned above, intramuscular (IM) tissue tends to affect the injected fluid 7 (e.g., injection solution) and disperse it mainly along the direction of muscle fiber extension M1. One particular advantage of the matrix array 815 is that its design allows for favorable IM electroporation results regardless of its orientation relative to the direction of muscle fiber extension M1. Thus, the matrix array 815 can be said to be more robust to misorientation in muscle.

[0052] As illustrated in Figure 9A, the matrix array 815 can be inserted into muscle tissue 675 in an orientation in which the electrode rows 817 are aligned with the direction of muscle fiber extension M1. This orientation can be characterized as a “parallel” or “0-degree” orientation. In this orientation, each electrode row 817 and associated injection channel 836 generally extends along and / or between the same muscle fibers 677. Three fluid injections (utilizing the injection channel 836) are dispersed mainly along the direction of muscle fiber extension M1, generally resulting in three aligned fluid dispersions 7. In this way, each of the electroporation pulses P1-P3 can effectively target its respective fluid dispersion 7 such that a large portion of the electroporation field colocalizes with its respective fluid dispersion 7.

[0053] As illustrated in Figure 9B, the matrix array 815 can alternatively be inserted into muscle tissue 675 in an orientation in which the electrode rows 817 are oriented perpendicular to the direction of muscle fiber extension M1. This orientation can be characterized as a “perpendicular” or “90-degree” orientation. In this orientation, each electrode row 817 can traverse multiple muscle fibers 677. Three fluid injections (utilizing injection channels 836) are dispersed primarily along the direction of muscle fiber extension M1, resulting in a longitudinally overlapping fluid dispersion 7 with the maximum concentration between electrodes E3 and E4. In this way, the electroporation pulses P1-P3 can effectively target more muscle fibers and contain more injected fluid than in the 0-degree orientation. Therefore, physicians can use the matrix array 815 in a 90-degree orientation to target more injection fluid in a more homogeneous electric field, which may lead to transfecting more muscle cells.

[0054] Referring here to Figure 9C, each electrode pair (i.e., electrodes in a single row 817) exhibits strong colocalization of the electroporation field and fluid dispersion, regardless of the array orientation relative to the direction of muscle fiber stretching M1. For example, in a 0-degree orientation, the high-magnitude portion of the electric field aligns with the high-concentration portion of the fluid dispersion 7. One reason for this result is that muscle fibers 677 exhibit the highest anisotropic electrical conductivity along the direction of muscle fiber stretching M1. Thus, the electrical impedance is minimized along direction M1. Additionally, muscle fibers provide lower mesohydrodynamic impedance along the direction of muscle fiber stretching M1, as described above. However, even when the orientation is rotated toward a higher angle, the injectable fluid still disperses along the direction of muscle fiber stretching M1, while the electric field deforms to somewhat coincide (due to its anisotropic and highest electrical conductivity along the fiber axis). Even in a 90-degree orientation, the electric field is effectively "stretched" in direction M1, resulting in an electric field that bulges in the center where the injectable fluid is located. Therefore, regardless of the orientation of array 815 relative to the muscle fibers, array 815 beneficially co-localizes the electric field with the injection solution.

[0055] In other embodiments of the matrix array 815, the number of electrode rows 817 and / or columns 819, and / or the number of injection channel rows 840 and / or columns 842 of the matrix array 815, may be reduced or increased as needed, based on various factors such as the target treatment location, target tissue, and injection volume, as a non-limiting example. For example, the matrix array 815 may be increased to include one or more additional rows 817 and / or columns 819 of electrodes, and / or one or more additional rows 840 and / or columns 842 of injection channels 836, such that row 840 of injection channels 836 aligns with row 817 of electrode 14. It should also be recognized that the matrix array 815 may use a combination of one or more injection channels 836 aligned with each electrode row 817 and one or more injection channels 836 offset from each electrode row 817 (including eccentric offset or equidistant offset).

[0056] It should be recognized that the various parameters of the injection needles 20, 625 and associated array assemblies 212, 312, 412, 612, 712, 812 and / or electrode arrays 215, 315, 415, 615, 715, 815 described herein are provided as exemplary features, such as to enhance the injection volume in the extended electroporation field and thereby enhance electropermeable transfection. These parameters can be adjusted as needed without departing from the scope of this disclosure. For example, the electrode arrays and chimney arrays shown represent non-limiting examples of possible array sizes and designs according to embodiments herein. Electrode arrays and chimney arrays can be used in substantially any array size (e.g., 15 × 15, 50 × 50, 100 × 100, and greater than 100 × 100). Furthermore, the array assemblies disclosed herein can be adapted so that their electrode arrays and chimney arrays can approximate the shape of the entire or partial shape of a patient's muscle, including, in non-limiting examples, the entire length of the patient's muscle, including long muscles such as the sartorius muscle. Furthermore, it should be recognized that electrode arrays and / or chimney arrays can be arranged in a variety of patterns, including alternating patterns, curved patterns, and irregular patterns, with varying and / or non-uniform spacing distances.

[0057] When numerical prepositions (e.g., “first,” “second,” “third”) are used herein in reference to elements, components, dimensions, or features thereof (e.g., “first” electrode, “second” electrode, “third” electrode), it should be understood that such numerical prepositions are used to distinguish the above elements, components, dimensions, and / or features from other such elements, components, dimensions, and / or features, and are not limited to the specific numerical prepositions used in the examples. For example, “first” electrode, direction, or support member may, as a non-limiting example, be referred to as “second” electrode, direction, or support member in a different context without departing from the scope of this disclosure, provided that the above elements, components, dimensions, and / or features remain appropriately distinguished in the context in which the numerical prepositions are used.

[0058] Although this disclosure has been described in detail, it should be understood that various modifications, substitutions, and alternatives can be made herein without departing from the spirit and scope of the invention as defined by the appended claims. Furthermore, the scope of this disclosure is not intended to be limited to the specific embodiments described herein. In particular, one or more features from the embodiments described above can be used in other embodiments herein. As will be readily apparent to those skilled in the art, existing or subsequently developed processes, machines, manufactures, compositions of materials, means, methods, or steps that perform substantially the same functions or achieve substantially the same results as the corresponding embodiments described herein can be utilized in accordance with this disclosure. This disclosure also includes the following aspects: [Aspect 1] An electrode array for use with an electroporation device, A support member having an upper surface and a bottom surface, wherein a plurality of injection channels extending from the upper surface to the bottom surface are defined, An electrode array comprising a plurality of needle electrodes, wherein the plurality of needle electrodes are coupled to a support member such that the distal ends of the plurality of needle electrodes extend to a needle depth below the bottom surface of the support member, the plurality of needle electrodes are arranged in a matrix pattern having rows and columns of the needle electrodes arranged along the support member, and the plurality of injection channels are dispersed within the matrix pattern of the needle electrodes. [Aspect 2] The electrode array according to embodiment 1, wherein the support member includes a plurality of tubular components extending outward from the upper surface, and the plurality of tubular components define the extensions of the plurality of injection channels. [Aspect 3] The electrode array according to embodiment 2, wherein the plurality of tubular components define outer ends configured to be fitted with complementary attachment components of an injection needle, so that when the attachment components of the injection needle are seated against the outer ends of the tubular components, the distal end of the injection needle extends to at least one second depth below the bottom surface. [Aspect 4] The electrode array according to embodiment 3, wherein the second depth is at least 0.5 mm smaller than the needle depth. [Aspect 5] The electrode array according to embodiment 3, wherein the second depth is at least 1.0 mm smaller than the needle depth. [Aspect 6] The electrode array according to embodiment 3, wherein the second depth is at least 5 mm smaller than the needle depth. [Aspect 7] The electrode array according to embodiment 1, wherein the matrix has four or more rows and two or more columns, and the support member defines at least two injection channels. [Aspect 8] The electrode array according to embodiment 1, wherein the matrix has five or more rows and two or more columns, and the support member defines at least two injection channels. [Aspect 9] The electrode array according to embodiment 1, wherein the matrix is ​​a 3x2 matrix having six needle electrodes arranged in three rows and two columns, and the support member defines three injection channels. [Aspect 10] The electrode array according to embodiment 10, wherein the three injection channels are arranged in a single row equidistant between the two rows of needle electrodes. [Aspect 11] The electrode array according to embodiment 11, wherein the three injection channels coincide with the three rows of the needle electrode. [Aspect 12] The electrode array according to embodiment 11, wherein the three injection channels are eccentrically offset from the three rows of needle electrodes by their respective offset distances. [Aspect 13] The electrode array according to embodiment 1, wherein the support member has a circuit that individually provides electrical communication to each of the plurality of needle electrodes so that a selected subset of needle electrodes are configured to deliver electroporation pulses. [Aspect 14] An electroporation device for inducing reversible electroporation in tissue cells, An electrode array, A support member having an upper surface and a bottom surface, wherein a plurality of injection channels extending from the upper surface to the bottom surface are defined, An electrode array comprising a plurality of needle electrodes, wherein the plurality of needle electrodes are coupled to the support member such that the distal ends of the plurality of needle electrodes extend to the needle depth below the bottom surface of the support member, the plurality of needle electrodes are arranged in a matrix pattern having rows and columns of the needle electrodes arranged along the support member, and the plurality of injection channels are dispersed within the matrix pattern of the needle electrodes, An electroporation device comprising: a plurality of injection needles configured to extend into the tissue through at least a plurality of injection channels. [Aspect 15] The electroporation device according to embodiment 14, further comprising an applicator having a handle and a mounting portion connected to the handle, wherein the electrode array is mountable to a mounting component, and the plurality of needle electrodes communicate with a circuit of the applicator to control the delivery of one or more electroporation pulses to the plurality of needle electrodes when the electrode array is mounted to the mounting component. [Aspect 16] The electroporation device according to embodiment 14, wherein the support member includes a plurality of tubular components extending outward from the upper surface, and the plurality of tubular components define the extensions of the plurality of injection channels. [Aspect 17] The electroporation device according to embodiment 16, wherein the plurality of tubular components define outer ends configured to be fitted with complementary attachment components of the injection needle, so that the distal end of the injection needle extends to at least one second depth below the bottom surface when the attachment components of the injection needle are seated against the outer ends of the tubular components. [Aspect 18] The electroporation device according to embodiment 17, wherein the second depth is at least 0.5 mm smaller than the first depth. [Aspect 19] The electroporation device according to embodiment 17, wherein the second depth is at least 1.0 mm smaller than the needle depth. [Aspect 20] The electroporation device according to embodiment 17, wherein the second depth is at least 5 mm smaller than the needle depth. [Aspect 21] The electroporation device according to embodiment 14, wherein the matrix has four or more rows and two or more columns, and the support member defines at least two injection channels. [Aspect 22] The electroporation device according to embodiment 1, wherein the support member has a circuit that individually provides electrical communication to each of the plurality of needle electrodes so that a selected subset of needle electrodes are configured to deliver electroporation pulses. [Aspect 23] An electroporation system for inducing reversible electroporation in tissue cells, An electrode array, A support member having an upper surface and a bottom surface, wherein a plurality of channels extending from the upper surface to the bottom surface are defined, An electropermeability system comprising an electrode array, which includes a plurality of needle electrodes, wherein the plurality of needle electrodes are coupled to the support member such that the distal ends of the plurality of needle electrodes extend to a needle depth below the bottom surface of the support member, and extend through a plurality of channels, wherein the plurality of needle electrodes are arranged in a matrix pattern having rows and columns of the needle electrodes arranged along the support member, and at least some of the plurality of needle electrodes are dual-purpose injection needle electrodes configured to inject a drug into the tissue and to deliver one or more electropermeability pulses to the tissue in order to cause the reversible electropermeation within the cells of the tissue. [Aspect 24] The electroporation system according to embodiment 23, further comprising an applicator having a handle and a mounting portion connected to the handle, wherein the electrode array is mountable to a mounting component, and the plurality of needle electrodes communicate with a circuit of the applicator to control the delivery of one or more electroporation pulses to the plurality of needle electrodes. [Aspect 25] The electroporation system according to embodiment 24, further comprising tubes connected to the dual-purpose injection needle electrode and in fluid communication with the dual-purpose injection needle electrode, wherein the tubes are configured to deliver an injection solution from a reservoir assembly to the dual-purpose injection needle electrode. [Aspect 26] The electroporation system according to embodiment 25, wherein all of the plurality of needle electrodes are dual-purpose injection needle electrodes.

Claims

1. An electrode array for use with an electroporation device, A support member having an upper surface and a lower surface, wherein the support member defines a plurality of injection channels extending from the upper surface to the lower surface, and includes a plurality of tubular components extending outward from the upper surface, the plurality of tubular components defining the extensions of the plurality of injection channels, A plurality of needle electrodes, wherein the plurality of needle electrodes are coupled to the support member such that the distal ends of the plurality of needle electrodes extend to the needle depth below the bottom surface of the support member, the plurality of needle electrodes are arranged in a matrix pattern having rows and columns of needle electrodes arranged along the support member, and the plurality of injection channels are dispersed within the matrix pattern of the needle electrodes, An electrode array in which the plurality of tubular components define outer ends configured to be attached to complementary attachment components of an injection needle, thereby, when the attachment components of the injection needle are seated against the outer ends of the tubular components, the distal end of the injection needle extends to at least one second depth below the bottom surface, the second depth being less than the needle depth.

2. The electrode array according to claim 1, wherein the matrix pattern has four or more rows and two or more columns, and the support member defines at least two injection channels.

3. The electrode array according to claim 1, wherein the matrix pattern has five or more rows and two or more columns, and the support member defines at least two injection channels.

4. The electrode array according to claim 1, wherein the matrix pattern is a 3x2 matrix having six needle electrodes arranged in three rows and two columns, and the support member defines three injection channels.

5. The electrode array according to claim 4, wherein the three injection channels are arranged in a single row equidistant from the two rows of needle electrodes.

6. The electrode array according to claim 5, wherein the three injection channels coincide with the three rows of needle electrodes.

7. The electrode array according to claim 5, wherein the three injection channels are eccentrically offset from the three rows of needle electrodes by their respective offset distances.

8. The electrode array according to claim 1, wherein the support member has a circuit that individually provides electrical communication to each of the plurality of needle electrodes so that a selected subset of needle electrodes are configured to deliver electroporation pulses.

9. An electroporation device for inducing reversible electroporation in tissue cells, An electrode array, A support member having an upper surface and a bottom surface, wherein the support member defines a plurality of injection channels extending from the upper surface to the bottom surface, and includes a plurality of tubular components extending outward from the upper surface, the plurality of tubular components defining the extensions of the plurality of injection channels, An electrode array comprising a plurality of needle electrodes, wherein the plurality of needle electrodes are coupled to the support member such that the distal ends of the plurality of needle electrodes extend to the needle depth below the bottom surface of the support member, the plurality of needle electrodes are arranged in a matrix pattern having rows and columns of the needle electrodes arranged along the support member, and the plurality of injection channels are dispersed within the matrix pattern of the needle electrodes, A plurality of injection needles configured to extend into the tissue through at least some of the plurality of injection channels, An electroporation device in which the plurality of injection needles are configured to be attached to at least some of the plurality of tubular components, so that when the injection needle attachment components are seated against the outer ends of the tubular components, the distal ends of the injection needles extend to at least one second depth below the bottom surface, the second depth being less than the needle depth.

10. The electroporation device according to claim 9, further comprising an applicator having a handle and a mounting portion extending from the handle, wherein the electrode array is attachable to the mounting portion, and the plurality of needle electrodes communicate with a circuit of the applicator to control the delivery of one or more electroporation pulses to the plurality of needle electrodes when the electrode array is attached to the mounting portion.

11. The electroporation device according to claim 9, wherein the matrix pattern has four or more rows and two or more columns, and the support member defines at least two injection channels.

12. The electroporation device according to claim 9, wherein the support member has a circuit that individually provides electrical communication to each of the plurality of needle electrodes so that a selected subset of needle electrodes are configured to deliver electroporation pulses.

13. An electroporation system for inducing reversible electroporation in tissue cells, An electrode array, A support member having an upper surface and a bottom surface, wherein a plurality of channels extending from the upper surface to the bottom surface are defined, and the support member includes a plurality of tubular components extending proximal from the upper surface to the outer ends of each of the plurality of tubular components, and the plurality of tubular components define the proximal extension of a first subset of the plurality of channels, A plurality of needle electrodes, wherein the plurality of needle electrodes are coupled to the support member such that the distal ends of the plurality of needle electrodes extend to the needle depth below the bottom surface of the support member, and the plurality of needle electrodes are arranged in a matrix pattern having rows and columns of needle electrodes arranged along the support member, An electrode array comprising a plurality of injection needles configured to extend into the tissue through a first subset of the plurality of channels, wherein the plurality of injection needles are configured to be attached to at least a portion of the outer ends of the plurality of tubular structures, and when the plurality of injection needles are seated against at least a portion of the outer ends of the plurality of tubular structures, the distal ends of the injection needles extend to at least one second depth below the bottom surface, the at least one second depth being less than the needle depth, An electroporation system in which at least some of the plurality of needle electrodes are dual-purpose injection needle electrodes extending through a second subset of the plurality of channels, configured to inject a drug into the tissue and to deliver one or more electroporation pulses to the tissue to cause the reversible electroporation within the cells of the tissue.

14. The electroporation system according to claim 13, further comprising an applicator having a handle and a mounting portion extending from the handle, wherein the electrode array is attachable to the mounting portion, and the plurality of needle electrodes communicate with a circuit of the applicator to control the delivery of one or more electroporation pulses to the plurality of needle electrodes when the electrode array is attached to the mounting portion.

15. The electroporation system according to claim 14, further comprising tubes connected to the dual-purpose injection needle electrode and in fluid communication with the dual-purpose injection needle electrode, wherein the tubes are configured to deliver an injection solution from a reservoir assembly to the dual-purpose injection needle electrode.

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