Non-conductive electric field guide for resection cavities, and systems and methods for using the same.

Abstract

A method for treating tumor cells around a resection cavity includes disposing a non-conductive material within the resection cavity adjacent to a target region. At least one first electrode and at least one second electrode are positioned relative to the tumor resection cavity such that an electric field between the at least one first electrode and the at least one second electrode passes through the target region. A tumor treating electric field is generated between the at least one first electrode and the at least one second electrode.

Description

Technical Field

[0001] Cross - reference to Related Applications This application claims the priority and benefit of the filing date of U.S. Provisional Patent Application No. 63 / 216,970, filed on June 30, 2021, which is hereby incorporated by reference in its entirety.

Background Art

[0002] Tumors can be treated by removing all or part of the tumor by resection, thereby leaving a resection cavity. Often, not all tumor cells are removed. For example, in the case of brain tumors such as glioblastoma, most of the tumor can be removed, but a part of the tumor (finger - like roots) may combine with normal cells. Thus, it is not possible to excise peripheral tumor cells without removing or destroying a substantial amount of normal cells, which may be undesirable.

[0003] Therefore, after removing most of the tumor, the remaining cells around the resection cavity (e.g., within the tumor periphery) can be treated by a secondary treatment process. One such treatment includes tumor treatment fields (TTFields). However, when most of the tumor is removed, a highly conductive fluid refills the cavity. Thus, a substantial portion of the TTFields passes directly through the fluid in the cavity, thereby reducing the effect of the TTFields when treating tumor cells around the cavity.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Non - Patent Documents

[0005] [Non-Patent Document 1] American Chemical Society. “A DNA-based nanogel for targeted chemotherapy.” ScienceDaily. ScienceDaily, November 18, 2020 www.sciencedaily.com / releases / 2020 / 11 / 201118141731.htm [Non-Patent Document 2] Niu, Kai et al. “Polypeptide nanogels with different functional cores promote chemotherapy of lung carcinoma.” Frontiers in pharmacology 10 (2019): 37 [Non-Patent Document 3] Sahu, Prashant et al. “Nanogels: a new dawn in antimicrobial chemotherapy.” Antimicrobial Nanoarchitectonics. Elsevier, 2017. pp. 101-137 [Overview of the project] [Means for solving the problem]

[0006] This specification describes a method comprising the step of placing a nonconductive material in a resection cavity adjacent to a target region in various embodiments. At least one first electrode and at least one second electrode can be positioned relative to the tumor resection cavity such that the electric field between them passes through the target region. A tumor therapeutic electric field can be generated between at least one first electrode and at least one second electrode.

[0007] In another embodiment, the system may comprise at least one first electrode, at least one second electrode, and a non-conductive material disposed between the at least one first electrode and the at least one second electrode. The signal generator can communicate electrically with each of the at least one first electrode and the at least one second electrode. The signal generator may be configured to generate an electric field between the at least one first electrode and the at least one second electrode.

[0008] In another embodiment, a non-conductive biocompatible material can be configured to receive the excision cavity. The non-conductive material can define an internal passage configured to be filled with a fluid to induce an electric field.

[0009] Further advantages of the present invention will be partially described below, partially evident from the description, or recognized by practicing the invention. The advantages of the present invention will be realized and achieved, in particular, by the elements and combinations indicated in the appended claims. It should be understood that both the above general description and the following detailed description are illustrative and descriptive only and do not limit the claimed invention.

[0010] These and other features of preferred embodiments of the present invention will become more apparent in a detailed description with reference to the accompanying drawings. [Brief explanation of the drawing]

[0011] [Figure 1] This is a schematic diagram of the treatment system disclosed herein, positioned on a patient. [Figure 2] These are schematic diagrams of tumors, resection cavities, and non-conductive materials disclosed herein. [Figure 3A] This specification provides a schematic diagram of electric field lines propagating between electrodes / transducers and around non-conductive materials. [Figure 3B] This is a model showing electric field lines around a non-conductive material. [Figure 4]Schematic diagram of an exemplary non-conductive material disclosed in this specification. [Figure 5] Model of the electric field distribution in the brain where the non-conductive material is disposed. [Figure 6] Model of the electric field distribution in the brain where the non-conductive material is not disposed. [Figure 7] Schematic diagram of a treatment system disclosed in this specification. [Figure 8] Schematic diagram showing a computing device communicating with an electric field generator disclosed in this specification.

Best Mode for Carrying Out the Invention

[0012] Next, the present invention will be described in more detail below with reference to the accompanying drawings. Although some implementations of the present invention are shown in the drawings, not all embodiments are shown. In fact, the present invention may be embodied in many different forms and should not be construed as limited to the embodiments described herein. Rather, these embodiments are provided so that this disclosure will satisfy the applicable legal requirements. The same numbers refer to the same elements throughout this specification. It should be understood that the specific methods and procedures described may be modified, and thus the present invention is not limited to such methods and procedures. Also, it should be understood that the terms used herein are for the purpose of describing particular embodiments only and are not intended to limit the scope of the present invention.

[0013] Those skilled in the art of the technology related to the present invention, having the benefit of the teachings presented in the above description and related drawings, will envision numerous modifications and other embodiments of the present invention described herein. Therefore, it should be understood that the present invention is not limited to the particular embodiments disclosed, and that modifications and other embodiments are intended to be included within the scope of the appended claims. Although specific terms are used herein, these terms are used only in a general and descriptive sense and not for purposes of limitation.

[0014] In this specification, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise. For example, when the term "an electrode" is used, it may refer to one or more such electrodes, and the same applies in other cases.

[0015] All technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains, unless otherwise clearly indicated.

[0016] In this specification, the terms "optional" or "optionally" mean that the subsequent described event or situation may or may not occur, and the description is meant to include instances where the event or situation occurs and instances where the event or situation does not occur.

[0017] In this specification, the term "at least one of" is intended to be synonymous with "one or more of". For example, "at least one of A, B, and C" explicitly includes only A, only B, only C, and each combination thereof.

[0018] In this specification, a range can be expressed as "approximately" from one specific value and / or "approximately" from another specific value. When such a range is expressed, another aspect includes one specific value and / or other specific values. Similarly, when a value is expressed as an approximation by using the antecedent "approximately", it will be understood that a specific value forms another aspect. It will be further understood that each endpoint of a range is significant with respect to and independently of the other endpoints. Optionally, in some aspects, when a value is approximated by using the antecedent "approximately", it may be considered that values ​​within a range of up to 15%, up to 10%, up to 5%, or up to 1% (above or below) the specifically stated value may be included within the range of those aspects. Similarly, in further embodiments, when values ​​are approximated by using “approximately,” “substantially,” and “roughly,” it is considered that values ​​within a range of up to 15%, up to 10%, up to 5%, or up to 1% of the specifically stated value (up to or below the specifically stated value) may be included within the range of those embodiments.

[0019] Unless otherwise indicated, the word “or” as used herein may mean any single element of a particular list, and in other optional forms may include any combination of elements of that list.

[0020] Unless otherwise specified, it should be understood that no method described herein is intended to be interpreted as requiring its steps to be performed in a specific order. Therefore, if a method claim does not actually describe the order in which each step of the method should be followed, and unless otherwise expressly stated in the claims or description that the steps are limited to a specific order, no order should be inferred in any respect. This applies to all possible implicit grounds for interpretation, including logical matters relating to the structure of the steps or workflow, obvious meanings derived from grammatical structure or punctuation, and the number or type of embodiments described in the specification.

[0021] The following description will include specific details for the sake of complete understanding. Nevertheless, those skilled in the art will understand that the apparatus, system, and associated methods of using the apparatus can be implemented and used without using these specific details. In fact, the apparatus, system, and associated methods can be implemented by modifying the illustrated apparatus, system, and associated methods and can be used in conjunction with any other apparatus and techniques used in conventional industry.

[0022] Figure 7 shows an exemplary apparatus 10 for electrotherapy disclosed herein. Generally, the apparatus may be a portable battery or power-operated device and generates an alternating electric field in the body by stimulation zones (e.g., transducer arrays or electrodes) as disclosed herein. Apparatus 10 may comprise an electric field generator 12 and one or more stimulation zones (shown as transducer arrays 14 in this exemplary configuration). Apparatus 10 may be configured to generate tumor therapeutic electric fields (TTFields) (e.g., 150 kHz) via the electric field generator 12 and to deliver the TTFields to a region of the body through the stimulation zones (e.g., one or more transducer arrays 14 or electrodes). The electric field generator 12 may be powered by a battery and / or power supply.

[0023] As shown in Figure 7, each transducer array 14 may comprise a plurality of electrodes or transducers 15. In this specification, unless otherwise indicated, features described in relation to electrodes are also applicable to transducers, and features described in relation to transducers are also applicable to electrodes. Thus, the terms electrode and transducer are used interchangeably in this specification. In exemplary embodiments, the transducer 15 can capacitively couple an AC signal into a body of interest. In further embodiments, the transducer 15 may comprise a layer of conductive material, such as a layer of at least one metal (e.g., steel, gold, and / or copper). Additionally or alternatively, the transducer 15 may comprise one or more layers of conductive adhesive (e.g., hydrogel). The exemplary transducer 15 may further comprise a dielectric material. Optionally, the transducer 15 may comprise a ceramic disc, such as that described in Patent Document 1, which is incorporated herein by reference. In additional or alternative embodiments, the transducer 15 may comprise a polymer insulating layer and / or other insulating material.

[0024] The electric field generator 12 may include a processor 16 that communicates with the signal generator 18. The electric field generator 12 may also include control software 20 configured to control the performance of the processor 16 and the signal generator 18.

[0025] The signal generator 18 may generate one or more electrical signals in the form of a waveform or pulse train. The signal generator 18 may be configured to generate AC voltage waveforms (e.g., TTFields) with frequencies in the range of about 50 kHz to about 1 MHz (preferably about 50 kHz to about 500 kHz or about 100 kHz to about 300 kHz). The voltage is such that the electric field strength in the tissue being treated is generally in the range of about 0.1 V / cm to about 10 V / cm.

[0026] One or more outputs 24 of the electric field generator 12 may be coupled to one or more conductive leads 22, one end of which is attached to the signal generator 18. Both ends of the conductive leads 22 are connected to one or more stimulation zones (e.g., transducer array 14) that are actuated by an electrical signal (e.g., a waveform). The conductive leads 22 may comprise standard insulated conductors including a flexible metal shield and may be grounded to prevent diffusion of the electric field generated by the conductive leads 22. One or more outputs 24 may be actuated sequentially. Output parameters of the signal generator 18 may include, for example, the electric field intensity, the frequency of the wave (e.g., a therapeutic frequency), and the maximum allowable temperature of one or more stimulation zones (e.g., transducer array 14). The output parameters may be set and / or determined by the control software 20 together with the processor 106. After determining a desired (e.g., optimal) therapeutic frequency, the control software 20 may cause the processor 16 to send a control signal to the signal generator 18, which causes the signal generator 18 to output the desired therapeutic frequency to one or more stimulation zones (e.g., transducer array 14). Similarly, the processor 16 may communicate with a thermistor (e.g., a thermometer or thermocouple) configured to measure the temperature in each transducer array, and when a temperature threshold is reached, the control software 20 may cause the processor 16 to reduce the frequency and / or intensity of the electrical signal provided by the signal generator 18. In a further embodiment, the processor 16 may communicate with a sensor configured to measure the intensity of the electric field generated by the device 10, and the control software 20 may cause the processor 16 to increase or decrease the frequency and / or intensity of the electrical signal to achieve a desired increase or decrease in the electric field intensity.

[0027] One or more stimulation zones (e.g., transducer array 14) may be configured in various shapes and positions to generate an electric field of a desired configuration, direction, and intensity in a target volume to concentrate the treatment. Optionally, one or more stimulation zones (e.g., transducer array 14) may be configured to deliver two perpendicular electric fields through the volume of interest (e.g., the target region).

[0028] Referring to Figures 1 and 2, the target region 50 can be a region adjacent to (optionally, surrounding) the resection cavity 52. ​​That is, at least a portion of the tumor can be resected (for example, in a resection surgery or other surgical procedure) to form the resection cavity 52. ​​A nonconductive material 54 can be placed in the resection cavity 52. ​​In this specification, the term “nonconductive material” refers to a material that is not conductive and does not induce an electric field. Optionally, the nonconductive material 54 can be implanted in the resection cavity 52 during the surgery in which the resection is performed. In a further embodiment, the nonconductive material 54 can be implanted in a subsequent surgery (separate from the surgery in which the resection is performed, but performed after the surgery in which the resection is performed). In a further embodiment, the nonconductive material 54 can be injected into the resection cavity 52 or introduced through a port or stent that allows access to the resection cavity 52. At least one first electrode 15a and at least one second electrode 15b can be positioned relative to the resection cavity 52 such that the electric field between at least one first electrode and at least one second electrode passes through the target region 50. For example, as shown in Figure 3A, in some optional embodiments, the first electrode 15a and the second electrode 15b can be positioned such that the resection cavity 52 is located between them. An electric field generator 12 can be used to generate a tumor-treating electric field 56 between at least one first electrode 15a and at least one second electrode 15b. Referring to Figures 3A and 3B, a nonconductive material 54 can cause the electric field 56 to avoid (avoid passing through), largely avoid, or at least partially avoid the resection cavity. Furthermore, the nonconductive material 54 can displace a volume generally filled with a conductive fluid (e.g., cerebrospinal fluid (CSF)), thereby eliminating a low-resistance path that would conventionally be available to the electric field in the absence of the nonconductive material. Therefore, using the non-conductive material 54 can increase the concentration of the tumor-treating electric field passing through the target region 50, thereby improving the efficacy of the treatment. For example, as shown in the models of Figures 5 and 6, the non-conductive material 54 can increase the concentration of the electric field surrounding the non-conductive material, which is indicated by the brighter region surrounding the black circle in Figure 5 compared to the region surrounding the black circle in Figure 6.

[0029] In various embodiments, the nonconductive material 54 can be biocompatible. In some optional embodiments, the nonconductive material 54 includes or can be embodied as a scaffold, hydrogel, film, or three-dimensional (3D) printed structure.

[0030] In embodiments where the nonconductive material 54 is a 3D printed construct, the nonconductive material may include either a hydrogel or a polyimide.

[0031] In embodiments where the nonconductive material 54 is a scaffold, the scaffold may optionally be a nanofiber scaffold or a hybrid scaffold. In some embodiments, the scaffold may optionally contain natural polymers. For example, the scaffold may contain one or more of hyaluronic acid, fibrin, chitosan, gelatin, agarose, collagen, or a combination thereof. In further embodiments, the scaffold may contain synthetic polymers. For example, the scaffold may contain one or more of polyethylene glycol (PEG), polypropylene fumarate (PPF), polyanhydride, polycaprolactone (PCL), polyphosphazene polyether ether ketone (PEEK), polylactic acid (PLA), poly(glycolic acid) (PGA), or a combination thereof.

[0032] In some embodiments, the scaffold can be a three-dimensional (3D) two-layer scaffold. The three-dimensional (3D) two-layer scaffold may optionally contain decellularized human amniotic membrane (AM) having viscoelastic electrospun nanofiber silk fibroin (ESF).

[0033] In some embodiments, the nonconductive material includes a biosheet (e.g., optionally, a silicone biosheet). The biosheet can optionally be a thin structure covering at least a portion of the surface defining the resection cavity. Thus, in some optionally, the biosheet can define and / or enclose an internal volume. Optionally, the internal volume of the biosheet can receive and fill fluid from the body. Optionally, the biosheet can include a mesh. In some optionally, the biosheet can coagulate after implantation. When in use, it is conceivable that the shape of the biosheet can be selectively adjusted to match or complement the shape of at least a portion of the resection cavity before it coagulates.

[0034] In some optional embodiments, the nonconductive material may comprise a chemotherapeutic agent configured to be released into a target region 50. For example, the chemotherapeutic agent may include taxanes such as paclitaxel(I), docetaxel(II), cabazitaxel(III), and any other taxane or taxane derivative, and non-limiting examples of these include taxol B (cephalomannin), taxol C, taxol D, taxol E, taxol F, taxol G, taxadiene, baccatin III, 10-deacetylbaccatin, taxitinin A, brevifoliol, and taxispin D, as well as pharmaceutically acceptable salts of taxanes. In further embodiments, the nonconductive material may include a nanogel. The nanogel may have one or more chemotherapeutic agents configured for slow release. For example, a DNA nanogel may include a structure that can be recognized and cleaved by the biomarker FEN1. Several exemplary nanogels for performing chemotherapy are presented in Non-Patent Document 1, which is incorporated herein by reference in its entirety. Further exemplary nanogels for performing chemotherapy are presented in Non-Patent Document 2, which is incorporated herein by reference in its entirety.

[0035] In some optional embodiments, the nonconductive material may contain an antimicrobial agent. Thus, the nonconductive material may serve the additional purpose of suppressing infection. Exemplary antimicrobial agents include, for example, macrolides, clindamycin, and doxycycline, without limitation. In some optional embodiments, one or more antimicrobial agents may be delivered using a nanogel, for example, as described in Non-Patent Document 3. This document is incorporated herein by reference in its entirety.

[0036] Optionally, the nonconductive material can be configured to decompose and be absorbed by the body (i.e., bioabsorbable). In a further embodiment, the nonconductive material can be configured not to decompose. Optionally, the nonconductive material 54 can be removed after treatment to act as a temporary insert. For example, after treatment with a desired amount (e.g., duration) of the nonconductive material, a stent or port can be made to reach the nonconductive material 54 to allow for removal of the nonconductive material. In this example, the stent or port is thought to extend through or be in fluid communication with an opening in a part of the patient's body (e.g., a hole formed in the patient's skull, or an access port formed in the patient's torso (e.g., abdomen or back)). In a further embodiment, the nonconductive material can be left indefinitely (or until the nonconductive material is absorbed by the body).

[0037] In some optional embodiments, the nonconductive material 54 may include oil. Thus, in some optional embodiments, the nonconductive material 54 may be a fluid that fills at least a portion of the excision cavity 52 and conforms to the shape of at least a portion of the excision cavity 52. ​​As further described herein, in further optional embodiments, the nonconductive material 54 may constitute both a rigid material and a fluid material.

[0038] Therefore, in some optional embodiments, the nonconductive material 54 may have a distinct structure and geometric shape. For example, optionally, the nonconductive material may be shaped to complement the geometric shape of the resection cavity. Optionally, the nonconductive material may be spherical. In further embodiments, the nonconductive material may be elliptical, cylindrical, polyhedron, irregular, or amorphous. In further embodiments, other shapes are intended depending on the anatomical structure and geometric shape of the resection cavity in the patient. Optionally, the nonconductive material 54 may support a material surrounding the resection cavity to prevent collapse of the resection cavity. In further embodiments, the nonconductive material may have a structure configured to conform to the shape of the resection cavity. In further embodiments, the nonconductive material 54 may include both a portion having a distinct structure and a fluid configured to conform to the shape of the resection cavity.

[0039] Depending on the size, shape, and location of the target region 50 and the resection cavity 52, in some (but not all) situations, the nonconductive material 54 forming a complete electric field barrier can result in a suboptimal distribution of the electric field across the entire target region. Thus, as also referring to Figure 4, in some optional embodiments, the nonconductive material 54 can be embodied as a nonconductor 55, including biocompatible materials. The nonconductor 55 can define at least one path through which the electric field passes. For example, in some embodiments, the nonconductor 55 is hollow and can define an outer surface 57 and an internal volume 58 (e.g., a shell with a thickness of less than 1 mm, about 1 mm, at least 1 mm, at least 2 mm, at least 3 mm, 5 mm or less, or greater than 5 mm). The nonconductor 55 may further comprise a plurality of openings 60 between the outer surface 57 and the internal volume 58 (or possibly providing fluid communication between the outer surface 57 and the internal volume 58). In these embodiments, the nonconductor 55 can be filled with a fluid (e.g., CSF) such that an internal volume 58 is defined between at least two of a plurality of openings 60 that can be optionally arranged on both sides of the nonconductor, thereby defining an internal passage 62. The internal passage 62 can induce an electric field. Furthermore, the internal passage 62 can converge and concentrate the electric field into the excision cavity and maintain an effective electric field intensity throughout the target region. Thus, as shown in Figure 4, a portion of the electric field 56 70 can enter the opening on one side of the nonconductor 55 and exit through the opening on the other side of the nonconductor (optionally, the opposite side). For example, a first plurality of openings (e.g., two, three, four, or five or more openings) can be arranged on the first side of the nonconductor 55, and a second plurality of openings (e.g., two, three, four, or five or more openings) can be arranged on the second side of the nonconductor (optionally, the opposite side). Optionally, the number of openings in the first set of openings can be equal to the number of openings in the second set of openings. In a further embodiment, each side of the nonconductor 55 may have a single opening 60 that is in fluid communication with the internal volume 58.In a further optional embodiment, the total area of ​​the openings on the first side of the nonconductor may be made equal to, or substantially equal to, the total area of ​​the openings on the second side of the nonconductor. Although described above as a single internal passage 62, the nonconductor 55 may define multiple internal passages, for example, each pair of openings may define at least first and second internal passages extending between each pair of openings, located on both sides of the nonconductor.

[0040] In some embodiments, multiple openings 60 can be arranged so as to be evenly distributed throughout the nonconductive material 55. In further embodiments, multiple openings 60 can optionally be concentrated in regions (e.g., clusters) located at both ends of the nonconductive material 55. The openings 60 can be formed in a scaffold, 3D printed structure, or biosheet. Optionally, the openings 60 can be circular (e.g., round or elliptical), rectangular slots, or any suitable shape. Optionally, each opening may be at least 1 mm 2 , at least 2mm 2 , 2mm 2 ~5mm 2 at least 5mm 2 , or 5mm 2 The nonconductive material 55 may have an area of ​​less than 10. The nonconductive material 55 may have two openings 60, at least two openings, at least four openings, at least six openings, at least ten openings, or fewer than ten openings. Optionally, the openings 60 may collectively have an area of ​​at least 5%, at least 10%, 20%, or 10% to 20% of the outer surface area of ​​the nonconductive material 55. In a further embodiment, the internal passage 62 may be defined by one or more bores or any other structure that penetrates the nonconductive material 55 or enables telecommunications.

[0041] In a further optional embodiment, the nonconductor 55 can define one or more paths that penetrate the nonconductor 55 and can be filled with a fluid. For example, the nonconductor 55 may include an open-cell foam that can be filled with a fluid. Thus, such a nonconductor 55 can prevent a portion of the electric field from passing through the nonconductor 55, thereby allowing a portion of the electric field to be directed along the outer periphery of the nonconductor.

[0042] The resection cavity may, optionally, be located within the patient's brain. In a further embodiment, the resection cavity may be located within the patient's liver. In a further embodiment, the resection cavity may be located within the patient's lungs. In a further embodiment, the resection cavity may be located within any part of the patient's body (for example, within any selected organ).

[0043] Referring to Figure 8, in several exemplary embodiments, a computing device 100 can be used to determine an optimal treatment plan in relation to the use of the disclosed nonconductive material 54. In these embodiments, the computing device 100 may comprise a processor 110 and a memory 120, the memory 120 storing processor-executable instructions that, when executed by the processor, cause the computing device to determine one or more features of an optimal treatment plan. Exemplary computing devices include, without limitation, personal computers, computing stations (e.g., workstations), portable computers (e.g., laptops, mobile phones, tablet devices), smart devices (e.g., smartphones, smartwatches, activity trackers, smart apparel, smart accessories), security and / or monitoring devices, servers, routers, network computers, peer devices, edge devices, or other common network nodes. In exemplary embodiments, the processor 110 of the computing device 100 may be communicably coupled (e.g., via a wired or wireless connection) to the processor 16 of the electric field generator 12 so that the computing device 100 can directly operate the electric field generator 12 to realize an optimal treatment plan. In these embodiments, the computing device 100 and the electric field generator 12 are thought to comprise, respectively, transmitters, receivers, transceivers, and / or cables configured to enable such communication. Alternatively, in other embodiments, the processor 16 of the electric field generator 12 may be configured to determine an optimal treatment plan in the manner of the disclosed computing device 100.

[0044] In exemplary embodiments, the computing device 100 may be configured to provide one or more of the following: optimal position for transducer placement, optimal electric field intensity, treatment duration, or electric field direction change and its timing. The computing device 100 may receive the geometric shape of at least a portion of the patient, including the resection cavity 52. ​​For example, the computing device 100 may receive a medical image of the patient. In further embodiments, the computing device 100 may receive a computer-generated model of the patient. In some optional embodiments, the geometric shape of the nonconductive material 54 may be provided to the computing device. The computing device 100 may be configured to model the electric field between transducers to optimize the treatment plan based at least partially on the path of the electric field to avoid the nonconductive material 54. The computing device 100 may be further configured to model the electric field based at least partially on the placement of transducers and / or the geometric shape of the nonconductive material and / or the geometric shape of the patient (e.g., the geometric shape of the resection cavity). The computing device 100 may optionally include a user interface (e.g., a display and / or user input device, without limitation) configured to allow the operator of the device to input information (e.g., one or more of the parameters described above) that can be used to determine and / or execute an optimal treatment plan. Further details of the computing device and platform for providing treatment plans are disclosed in Patent Document 2, filed December 12, 2017. Patent Document 2 is incorporated herein by reference in its entirety for any purpose.

[0045] Exemplary aspects In view of the products, systems, and methods described herein, as well as their variations, several aspects of the present invention will be described in more detail below. However, these aspects described in detail should not be construed as having any limiting effect on any different claims, including different or more general teachings, as described herein, nor should the “particular” aspects be construed as being limited in any respect other than the inherent meaning of the wording used literally herein.

[0046] Appearance 1: The steps include placing a non-conductive material in the resection cavity adjacent to the target region, The steps include positioning at least one first electrode and at least one second electrode within the tumor resection cavity such that the electric field between them passes through the target region, The steps include generating a tumor treatment electric field between at least one first electrode and at least one second electrode, Methods that include...

[0047] Embodiment 2: The method according to Embodiment 1, wherein each of the at least one first electrode and the at least one second electrode comprises a plurality of electrodes arranged in their respective electrode arrays.

[0048] Embodiment 3: The method according to Embodiment 1 or 2, wherein the nonconductive material comprises at least one of a scaffold, hydrogel, film, or 3D printed structure.

[0049] Embodiment 4: The method according to Embodiment 3, wherein the nonconductive material is a 3D printed construct, and the 3D printed construct comprises either a hydrogel or a polyimide.

[0050] Embodiment 5: The method according to Embodiment 3, wherein the non-conductive material includes a scaffold.

[0051] Embodiment 6: The method according to Embodiment 5, wherein the scaffold is either a nanofiber scaffold or a hybrid scaffold.

[0052] Embodiment 7: The method according to Embodiment 5 or 6, wherein the scaffold comprises a natural polymer.

[0053] Embodiment 8: The method according to Embodiment 7, wherein the natural polymer comprises one or more of hyaluronic acid, fibrin, chitosan, gelatin, agarose, or collagen.

[0054] Embodiment 9: The method according to Embodiment 5 or 6, wherein the scaffold comprises a synthetic polymer.

[0055] Embodiment 10: The method according to Embodiment 9, wherein the synthetic polymer comprises polyethylene glycol (PEG), polypropylene fumarate (PPF), polyanhydride, polycaprolactone (PCL), polyphosphazene, polyetheretherketone (PEEK), polylactic acid (PLA), poly(glycolic acid) (PGA), or a combination thereof.

[0056] Embodiment 11: The method according to Embodiment 3, wherein the scaffold is a three-dimensional (3D) two-layer scaffold containing biodegraded human amniotic membrane (AM) containing viscoelastic electrospun nanofiber silk fibroin (ESF).

[0057] Embodiment 12: The method according to any one of Embodiments 1 to 11, wherein the nonconductive material includes a biosheet.

[0058] Embodiment 13: The method according to Embodiment 12, wherein the biosheet is a silicone sheet.

[0059] Embodiment 14: The method according to any one of Embodiments 1 to 13, wherein the nonconductive material comprises a chemotherapeutic agent.

[0060] Embodiment 15: The method according to any one of Embodiments 1 to 14, wherein the nonconductive material comprises an antimicrobial agent.

[0061] Embodiment 16: The method according to any one of Embodiments 1 to 15, wherein the nonconductive material comprises an oil.

[0062] Embodiment 17: The method according to any one of Embodiments 1 to 16, wherein the nonconductive material defines an internal passage configured to be filled with a fluid to induce an electric field.

[0063] Embodiment 18: The method according to Embodiment 17, wherein the nonconductive material comprises a hollow body defining an internal volume and at least a first opening and a second opening extending into the internal volume of the hollow body, and the internal passage is at least partially defined by the first opening, the second opening and the internal volume.

[0064] Embodiment 19: The method according to any one of embodiments 1 to 18, further comprising the step of excising at least a portion of the tumor to form an excision cavity before placing a nonconductive material into the excision cavity.

[0065] Embodiment 20: The resection cavity is located in the brain, according to any one of Embodiments 1 to 19.

[0066] Embodiment 21: The resection cavity is located within the liver, according to any one of Embodiments 1 to 19.

[0067] Embodiment 22: The resection cavity is located within the lung, according to any one of Embodiments 1 to 19.

[0068] Appearance 23: A step of providing a port from the resection cavity through which a non-conductive material can pass, The steps include generating a tumor treatment electric field between at least one first electrode and at least one second electrode, and then removing a non-conductive material from the resection cavity by passing it through a port, The method according to any one of embodiments 1 to 22, further comprising:

[0069] Embodiment 24: The method according to Embodiment 23, further comprising the step of passing a non-conductive material through a port and placing it in the resection cavity.

[0070] Appearance 25: At least one first electrode, At least one second electrode, A signal generator that electrically communicates with at least one first electrode and at least one second electrode, the signal generator configured to generate an electric field between the at least one first electrode and the at least one second electrode, A non-conductive material disposed between at least one first electrode and at least one second electrode, A system equipped with these features.

[0071] Embodiment 26: The system according to Embodiment 25, wherein the nonconductive material defines an internal passage configured to be filled with a fluid to induce an electric field.

[0072] Embodiment 27: The system according to Embodiment 26, wherein the nonconductive material comprises a hollow body defining an internal volume and at least a first opening and a second opening extending into the internal volume of the hollow body, and the internal passage is at least partially defined by the first opening, the second opening and the internal volume.

[0073] Embodiment 28: The system according to any one of embodiments 25 to 27, wherein each of at least one first electrode and at least one second electrode comprises a plurality of electrodes arranged on their respective electrode arrays.

[0074] Embodiment 29: The system according to any one of Embodiments 25 to 28, wherein the nonconductive material comprises at least one of a scaffold, a hydrogel, a film, or a 3D printed construct.

[0075] Embodiment 30: The system according to Embodiment 29, wherein the nonconductive material is a 3D printed construct, and the 3D printed construct comprises either a hydrogel or a polyimide.

[0076] Embodiment 31: The system according to Embodiment 29, wherein the nonconductive material includes a scaffold.

[0077] Embodiment 32: The system according to Embodiment 31, wherein the scaffold is either a nanofiber scaffold or a hybrid scaffold.

[0078] Embodiment 33: The system according to Embodiment 31 or 32, wherein the scaffold comprises a natural polymer.

[0079] Embodiment 34: The system according to Embodiment 33, wherein the natural polymer comprises one or more of hyaluronic acid, fibrin, chitosan, gelatin, agarose, or collagen.

[0080] Embodiment 35: The system according to Embodiment 31 or 32, wherein the scaffold comprises a synthetic polymer.

[0081] Embodiment 36: The system according to Embodiment 35, wherein the synthetic polymer comprises polyethylene glycol (PEG), polypropylene fumarate (PPF), polyanhydride, polycaprolactone (PCL), polyphosphazene, polyetheretherketone (PEEK), polylactic acid (PLA), poly(glycolic acid) (PGA), or a combination thereof.

[0082] Embodiment 37: The system according to Embodiment 29, wherein the scaffold is a three-dimensional (3D) two-layer scaffold containing biodegraded human amniotic membrane (AM) containing viscoelastic electrospun nanofiber silk fibroin (ESF).

[0083] Embodiment 38: The system according to any one of Embodiments 25 to 37, wherein the nonconductive material includes a biosheet.

[0084] Embodiment 39: The system according to Embodiment 38, wherein the biosheet is a silicone sheet.

[0085] Embodiment 40: A system according to any one of Embodiments 25 to 39, wherein the nonconductive material comprises a chemotherapeutic agent.

[0086] Embodiment 41: The system according to any one of Embodiments 25 to 40, wherein the nonconductive material comprises an antimicrobial agent.

[0087] Embodiment 42: The system according to any one of Embodiments 25 to 41, wherein the nonconductive material includes an oil.

[0088] Embodiment 43: The system according to any one of Embodiments 27 to 42, wherein the first opening and the second opening are located on both sides of the hollow body.

[0089] Embodiment 44: The system according to any one of Embodiments 25 to 43, further comprising a computing device that communicates with a signal generator.

[0090] Embodiment 45: A device comprising a nonconductor containing a biocompatible material, the nonconductor comprising an internal passage configured to be received into a resection cavity and to be filled with a fluid to induce an electric field.

[0091] Embodiment 46: The apparatus according to Embodiment 45, wherein the nonconductor is hollow and defines an internal volume and at least a first opening and a second opening extending into the internal volume of the nonconductor, and the internal passage is at least partially defined by the first opening, the second opening and the internal volume.

[0092] While the above invention has been described in some detail as an example and illustration for the purpose of clarifying understanding, certain changes and modifications may be made within the scope of the attached claims. [Explanation of Symbols]

[0093] 10 equipment 12. Electric field generator 14 transducer arrays 15 Transducers 15a First electrode 15b Second electrode 16 processors 18 Signal Generator 20 Control Software 22 Conductive lead wires 24 outputs 50 target area 52 Resection cavity 54 Non-conductive materials 55 Nonconductive 56 Tumor treatment electric field, electric field 57 Exterior 58 Internal volume 60 opening 62 Internal passage 70 Part of the electric field 100 Computing Devices 110 processors 120 memory

Claims

1. At least one first electrode and At least one second electrode, A signal generator that electrically communicates with each of the at least one first electrode and the at least one second electrode, the signal generator configured to generate an electric field between the at least one first electrode and the at least one second electrode, A nonconductive material disposed between the at least one first electrode and the at least one second electrode, defining an internal passage configured to be filled with a fluid to induce an electric field, A system equipped with these features.

2. The system according to claim 1, wherein the nonconductive material comprises a hollow body defining an internal volume and at least a first opening and a second opening extending into the internal volume of the hollow body, and the internal passage is at least partially defined by the first opening, the second opening and the internal volume.

3. The system according to claim 1 or 2, wherein each of the at least one first electrode and the at least one second electrode comprises a plurality of electrodes arranged on their respective electrode arrays.

4. The system according to claim 1 or 2, wherein the nonconductive material is a 3D printed construct, and the 3D printed construct comprises either a hydrogel or a polyimide.

5. The system according to claim 1 or 2, wherein the nonconductive material includes a scaffold.

6. The system according to claim 5, wherein the scaffold comprises a natural polymer, the natural polymer comprising one or more of hyaluronic acid, fibrin, chitosan, gelatin, agarose, or collagen.

7. The system according to claim 5, wherein the scaffold comprises a synthetic polymer, the synthetic polymer comprising polyethylene glycol (PEG), polypropylene fumarate (PPF), polyanhydride, polycaprolactone (PCL), polyphosphazene, polyetheretherketone (PEEK), polylactic acid (PLA), poly(glycolic acid) (PGA), or a combination thereof.

8. The system according to claim 5, wherein the scaffold is a three-dimensional (3D) two-layer scaffold containing biodegraded human amniotic membrane (AM) containing viscoelastic electrospun nanofiber silk fibroin (ESF).

9. The system according to claim 1 or 2, wherein the nonconductive material includes a biosheet.

10. The system according to claim 9, wherein the biosheet is a silicone sheet.

11. The system according to claim 1 or 2, wherein the nonconductive material comprises a chemotherapeutic agent.

12. The system according to claim 1 or 2, wherein the non-conductive material includes an antibacterial agent.

13. The system according to claim 1 or 2, wherein the non-conductive material includes oil.

14. The system according to claim 2, wherein the first opening and the second opening are located on both sides of the hollow body.

15. The system according to claim 1 or 2, further comprising a computing device that communicates with the signal generator.

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