Constructing a 3D phantom using liquid hydrogel

Abstract

Described herein is a hydrogel phantom. The hydrogel phantom includes a plurality of adjacently arranged hydrogel elements. A first one of the hydrogel elements has a first electrical impedance and a second one of the hydrogel elements has a second impedance. The first impedance is different from the second impedance.

Description

Technical Field

[0001] Cross-Reference to Related Applications / Incorporation by Reference This patent application claims priority to a provisional patent application identified by U.S. Patent Application No. 63 / 162,921, filed on March 18, 2021. The entire content of U.S. Patent Application No. 63 / 162,921 is incorporated herein by reference.

[0002] Description of Research and Development Sponsored by Federal Funds Not applicable.

Background Art

[0003] Tumor treating fields (TTFields or TTFs) are low-intensity (e.g., 1 - 3 V / cm) alternating electric fields in the intermediate frequency range (100 - 500 kHz) that attack solid tumors by disrupting mitosis. This non-invasive treatment targets solid tumors and is described, for example, in U.S. Patent Nos. 7,016,725; 7,089,054; 7,333,852; 7,565,205; 8,244,345; 8,715,203; 8,764,675; 10,188,851; and 10,441,776. TTFields are typically delivered through two pairs of transducer arrays that generate perpendicular electric fields within the treated tumor; the transducer arrays that make up each of these pairs are positioned on opposite sides of the body part being treated. TTFields are approved for the treatment of glioblastoma multiforme (GBM) and can be delivered, for example, via the OPTUNE® system (Novocure Limited, St. Helier, Jersey), which includes transducer arrays placed on the shaved head of a patient.

[0004] Each transducer array used for TTField delivery within the OPTUNE® device comprises a set of non-conductive ceramic disc electrodes, which are bonded to the patient's skin (e.g., the patient's shaved head for the treatment of GBM) through a layer of conductive medical gel. To form the ceramic disc electrodes, a conductive layer is formed on the upper surface of the non-conductive ceramic material. The bottom surface of the non-conductive ceramic material is bonded to the conductive medical gel.

[0005] One approach to applying a TTField in different directions is to apply an electric field between a first set of electrodes over a predetermined period of time, then apply an electric field between a second set of electrodes over a predetermined period of time, and then repeat that cycle over a longer duration (e.g., over several days or weeks). To generate a TTField, a current is applied to each electrode of the transducer array. The TTField interacts with the patient and one or more of the patient's organs based on the electrical conductivity of each of the patient's organs. As the TTField interacts with the patient, the electric field can change shape, partly based on the electrical conductivity and relative position of each of the patient's organs. It is important that we can determine how the applied TTField will shape within the patient, as the electrical conductivity of each of the patient's organs modifies the TTField shape, and a specific TTField shape may be required to effectively target and attack a tumor.

[0006] Currently, there is no way to measure the actual TTField shape in a patient without computer simulation; however, computer simulations or other models rely on programming techniques and estimations and cannot accurately represent the expected actual TTField shape in a patient.

[0007] Since the electrical conductivity of each patient's organs may modify the TTField shape, potentially requiring specific TTField shapes to effectively target and attack tumors, there is a need for novel and improved assemblies and methods that use physical 3D models to determine the real-world interaction between the TTField and various organs. This disclosure relates to such assemblies as well as methods for producing and using them. [Prior art documents] [Patent Documents]

[0008] [Patent Document 1] U.S. Patent No. 7,016,725 [Patent Document 2] U.S. Patent No. 7,089,054 [Patent Document 3] U.S. Patent No. 7,333,852 [Patent Document 4] U.S. Patent No. 7,565,205 [Patent Document 5] U.S. Patent No. 8,244,345 [Patent Document 6] U.S. Patent No. 8,715,203 [Patent Document 7] U.S. Patent No. 8,764,675 [Patent Document 8] U.S. Patent No. 10,188,851 [Patent Document 9] U.S. Patent No. 10,441,776 [Patent Document 10] U.S. Patent Application No. 63 / 020,636 [Patent Document 11] U.S. Patent Publication No. 2020 / 0146586 [Patent Document 12] U.S. Patent Publication No. 2020 / 0023179 [Overview of the project] [Means for solving the problem]

[0009] The present invention constructs a 3D phantom with a liquid hydrogel.

Brief Description of the Drawings

[0010] [Figure 1] It is a diagram showing an exemplary embodiment of a schematic diagram of an electrode as applied to a biological tissue. [Figure 2] It is a diagram showing an exemplary embodiment of an electronic device configured to generate TTFields. [Figure 3A] It is a cross-sectional diagram of an exemplary embodiment of a hydrogel phantom. [Figure 3B] It is a cross-sectional diagram of another exemplary embodiment of a hydrogel phantom. [Figure 4A] It is a diagram of an exemplary embodiment of a gel application system constructed in accordance with the present disclosure. [Figure 4B] It is a diagram of an exemplary embodiment of a second gel application system constructed in accordance with the present disclosure. [Figure 5] It is a process flow diagram of an exemplary embodiment of a hydrogel phantom generation process. [Figure 6] It is a process flow diagram of an exemplary embodiment of an electric field generating pad placement process. [Figure 7] It is a flowchart of an exemplary method for verifying a computer simulation using a hydrogel phantom according to the present disclosure.

Modes for Carrying Out the Invention

[0011] When used in accordance with the present disclosure, the following terms shall be understood to have the following meanings, unless otherwise indicated:

[0012] The use of the terms "a" or "an" in the claims and / or specification with the term "comprising" may mean "one," but it is also consistent with the meanings of "one or more," "at least one," and "one or two or more." Thus, the terms "a," "an," and "the" include multiple referents unless the context explicitly indicates otherwise. For example, a reference to "a compound" may refer to one or more compounds, two or more compounds, three or more compounds, four or more compounds, or more than that number of compounds. The term "multiple" means "two or more."

[0013] The use of the term "at least one" is understood to include one and any two or more quantities, including, but not limited to, 2, 3, 4, 5, 10, 15, 20, 30, 40, 50, 100, etc. In addition, the use of the term "at least one of X, Y, and Z" is understood to include X alone, Y alone, and Z alone, as well as any combination of X, Y, and Z. The use of ordinal terminology (i.e., "first," "second," "third," "fourth," etc.) is solely for the purpose of differentiating between two or more items and does not imply, for example, any sequence or order or importance of one item relative to another, or any additional order.

[0014] The use of the term “or” in the claims is used to mean an inclusive “and / or” unless it is explicitly indicated to refer only to the options, or unless the options are mutually exclusive. For example, the condition “A or B” is satisfied by any of the following: A is true (or exists) and B is false (or does not exist); A is false (or does not exist) and B is true (or exists); and both A and B are true (or exist).

[0015] Any reference to “one embodiment,” “a certain embodiment,” “several embodiments,” “one example,” “for example,” or “a certain example,” as used herein, means that a particular element, feature, structure, or characteristic described in relation to an embodiment is included in at least one embodiment. Occurrences of the phrases “in several embodiments” or “one example” in various places within this specification do not necessarily all refer to the same embodiment, for example. Furthermore, all references to one or more embodiments or examples should be interpreted as not limiting the scope of the claims.

[0016] Throughout this application, the term "approximately" is used to indicate that the value includes inherent variations in errors relating to the composition / apparatus / device, the method used to determine the value, or the variations present between the subjects under consideration.

[0017] When used herein and in the claims, the words “comprising” (and any form of “comprising,” such as “comprise” and “comprises”), “having” (and any form of “having,” such as “have” and “has”), “including” (and any form of “including,” such as “includes” and “include”), or “containing” (and any form of “containing,” such as “contains” and “contain”) are either inclusive or open-ending and do not exclude any additional, undescribed elements or method steps.

[0018] The terms “or any combination thereof” as used herein refer to all permutations and combinations of the items listed preceding the term. For example, “A, B, C, or any combination thereof” includes at least one of A, B, C, AB, AC, BC, or ABC, and is also intended to include BA, CA, CB, CBA, BCA, ACB, BAC, or CAB, where the order is important in the particular context.

[0019] As used herein, all numbers or ranges include values ​​and integer fractions within such ranges, as well as integer fractions within such ranges, unless the context explicitly indicates otherwise. Therefore, for illustrative purposes, references to numerical ranges such as 1 to 10 include 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 1.1, 1.2, 1.3, 1.4, 1.5, etc.

[0020] As used herein, the term “substantially” means that the events or circumstances described thereafter occur completely, or that the events or circumstances described thereafter occur to a large extent or degree.

[0021] As used herein, the terms “associated with” and “connected to” include both direct association / connection of two parts to each other and indirect association / connection of two parts to each other.

[0022] The term “patient” as used herein includes human and veterinary subjects. “Mammal” for therapeutic purposes means any animal classified as a mammal, which includes (but not limited to) humans, livestock, and farm animals, non-human primates, and any other animals having mammary gland tissue.

[0023] As used herein, a circuit can be an analog and / or digital component, or one or more appropriately programmed processors (e.g., microprocessors) and associated hardware and software, or hardwired logic. Furthermore, a “component” can perform one or more functions. The term “component” can include hardware (e.g., processors (e.g., microprocessors), application-specific integrated circuits (ASICs), field-programmable gate arrays (FPGAs), etc.), and / or combinations of hardware and software. The term “processor” as used herein means a single or multiple processors working independently or together to collectively perform a task.

[0024] The term "resistance" or "resistivity" refers to the degree to which a material or device resists the passage of an electric current that causes energy dissipation.

[0025] The term "impedance" refers to the effective resistance of an electrical circuit or component to alternating current, resulting from the combined effect of ohmic resistance and reactance.

[0026] The term "conductivity" refers to the degree to which a particular material conducts electricity, and it is calculated as the ratio of the current density in the material to the electric field that causes the flow of current. The "conductivity" of a material is the reciprocal of its resistivity.

[0027] Referring here to the drawings, in particular Figure 1, therein is a diagram of an exemplary embodiment of a dividing cell 10 under the influence of an external TT Field (e.g., an alternating electric field in the frequency range of about 100 kHz to about 300 kHz), generally indicated by lines of force 14, generated by a first electrode 18a having a negative charge and a second electrode 18b having a positive charge. Microtubules 22, which are known to have a very strong dipole moment, are further shown. This strong polarization makes the microtubules 22, as well as other polar macromolecules, and in particular those having a specific orientation within or around the cell 10, susceptible to the influence of the electric field. The positive charge of the microtubule 22 is located in two centrioles 26, while two sets of negative poles are located at the center 30 of the dividing cell 10 and at the point of attachment 34 of the microtubule 22 to the cell membrane. The locations of the charges form a set of bidipoles and are therefore susceptible to the influence of electric fields in opposite directions. While the direction of the electric field can be adjusted by adjusting the positions of the first electrode 18a and the second electrode 18b relative to the dividing cell 10, interactions between the electric field and one or more cells or organelles between each electrode 18 and the dividing cell may cause changes in the electric field (e.g., deflection of the electric field).

[0028] Looking at Figure 2, the TTField described above, which has been found to favorably destroy tumor cells, is generated by the electronic device 50. Figure 2 is a simple schematic diagram of the electronic device 50 illustrating its main components. The electronic device 50 includes a generator 54 and a pair of conductive leads 58 (including a first conductive lead 58a and a second conductive lead 58b). The first conductive lead 58a includes a first end 62a and a second end 62b. The second conductive lead 58b includes a first end 66a and a second end 66b. The first end 62a of the first conductive lead 58a is conductively attached to the generator 54, and the first end 66a of the second conductive lead 58b is conductively attached to the generator 54. The generator 54 generates a desired electrical signal (TT signal) in the shape of a waveform or a string of pulses as an output. The second end 62b of the first conductive lead 58a is connected to the first electric field generating pad 70a, and the second end 66b of the second conductive lead 58b is connected to the second electric field generating pad 70b, which is supplied with an electrical signal (e.g., a waveform). Each of the first electric field generating pad 70a and the second electric field generating pad 70b is in contact with or otherwise associated with the electric field target 74. The electrical signal generates an electric field (i.e., TTField) capacitively connected into the electric field target 74, the TTField having frequency and amplitude, which is generated between the first electric field generating pad 70a and the second electric field generating pad 70b in the electric field target 74. In one embodiment, the electric field target 74 is a hydrogel phantom 78 which generally includes two or more hydrogel elements 82a-n shown in Figure 2 as hydrogel elements 82a and 82b, which are described in more detail below.

[0029] Each of the first electric field generating pad 70a and the second electric field generating pad 70b includes one or more conductive electrode elements which can be capacitively coupled to the electric field target 74 by a nonconductive layer. Alternative constructs may also be used for the first electric field generating pad 70a and the second electric field generating pad 70b, which include, for example, transducer arrays using nonconductive layers made of a nonconductive layer formed from a disk-shaped (or non-disk-shaped) ceramic element, and / or a nonconductive layer using a non-ceramic dielectric material positioned on a plurality of flat conductors. An example of the latter includes a polymer film which is disposed on a pad on a printed circuit board or on a flat piece of metal. Furthermore, the first electric field generating pad 70a and the second electric field generating pad 70b may also include electrode elements that are not capacitively coupled to the electric field target 74. In this configuration, each of the first electric field generating pad 70a and the second electric field generating pad 70b can be implemented using a region of conductive material configured to be placed against a human body without an insulating dielectric layer disposed between the conductive element and the body. Examples of conductive materials include, but are not limited to, conductive films, conductive fabrics, and / or conductive foams. Other alternative constructs for implementing the first electric field generating pad 70a and the second electric field generating pad 70b can also be used, as long as they can deliver the TTField to the human body. Optionally, a layer of hydrogel can be disposed between the first electric field generating pad 70a and the electric field target 74; and between the second electric field generating pad 70b and the electric field target 74 in any of the embodiments described herein.

[0030] The generator 54 generates an AC voltage waveform (i.e., TTField) at a frequency in the range of approximately 50 kHz to approximately 1 MHz (preferably, approximately 100 kHz to approximately 300 kHz). The required voltage is such that the electric field strength in the tissue within the target region is in the range of approximately 0.1 V / cm to approximately 10 V / cm. To realize this electric field, the potential difference between the two electrodes 18 of the first electric field generating pad 70a and the second electric field generating pad 70b is determined by the relative impedance of the system components; that is, the electric field fraction for each component is given by dividing the impedance of that component by the total circuit impedance.

[0031] In certain (but non-limiting) embodiments, the first electric field generating pad 70a and the second electric field generating pad 70b generate an alternating current electric field within the target region of the electric field target 74. The alternating current electric field can be selected to emulate one or more sources of electromagnetic radiation. For example, to simulate a TTField, the alternating current electric field can be selected to emulate a TTField (as described below). In other embodiments, for example, when simulating electromagnetic radiation supplied by a mobile phone, a mobile phone communication radio signal is generated as an alternating current electric field. Simulating electromagnetic radiation supplied by a mobile phone may be particularly necessary when measuring the specific absorption rate of a particular mobile phone.

[0032] In certain (but non-limiting) embodiments, when the electric field target 74 is a patient, the target region can typically include at least a portion of the patient's body and also be a portion of the patient's body having a foreign body such as a tumor, a specific cell or cluster of cells of the same or different type, a virus or bacteria, and / or similar (for example, only such a portion), and the generation of an alternating electric field selectively destroys or inhibits the growth of the tumor. The alternating electric field can be generated at any frequency that selectively destroys or inhibits the growth of the tumor.

[0033] To optimize the distribution of the electric field (i.e., TTField), the first electric field generating pad 70a and the second electric field generating pad 70b (a pair of electric field generating pads 70) can be configured or oriented differently depending on the application in which the pair of electric field generating pads 70a and 70b will be used. As described herein, the pair of electric field generating pads 70a and 70b are applied externally to an electric field target 74. When the electric field target 74 is a patient, the pair of electric field generating pads 70 can be applied to the patient's skin to apply an electric current and electric field (TTField), thereby generating an electric current within the patient's tissue. Generally, the pair of electric field generating pads 70 are placed by the user on the patient's skin so that the electric field is generated across the patient's tissue within the treatment area. The externally applied TTField can be of a localized type or a broadly distributed type, for example, in the treatment of skin tumors and lesions close to the skin surface. Similarly, the electric field applied to the electric field target 74 can be of a localized type or a widely distributed type.

[0034] According to optional and other exemplary embodiments, the electronic device 50 includes a control box 86 and a temperature sensor 90 connected to the control box 86, which are included for controlling the amplitude of the electric field.

[0035] When a control box 86 is included, the control box 86 controls the output of the generator 54, causing the output to remain constant at a value preset by the user. Alternatively, the control box 86 sets the output of the generator 54. A temperature sensor 90 can be mechanically connected to and / or otherwise associated with the first electric field generating pad 70a or the second electric field generating pad 70b, and is configured to sense the temperature of the electric field target 74 in either or both of the first electric field generating pad 70a or the second electric field generating pad 70b.

[0036] The conductive lead 58 is a standard isolated conductor with a flexible metal shield, preferably grounded to prevent any spreading of the electric field generated by the conductive lead 58. The electric field generating pads 70a and 70b can have a specific shape and positioning, and are configured to generate a TTField of a desired configuration, direction, and intensity in a target region of the electric field target 74, and to concentrate the electric field only there.

[0037] The specifications of the electronic device 50 as a whole, and the specifications of its individual components, are greatly influenced by the fact that, at frequencies in the TTField (e.g., 50 kHz to 500 kHz), biological systems behave according to their "Ohm's Law" rather than their dielectric properties.

[0038] Figures 3A and 3B illustrate exemplary embodiments of the hydrogel phantom 78 of Figure 2. In some embodiments, the hydrogel phantom 78 can be formed in the shape of a human or non-human body part (e.g., an arm, elbow, chest, leg, and torso, or a combination thereof) or in the shape of another type of object (e.g., a cell phone, or a portion of a wall). In some embodiments, the hydrogel phantom 78 is formed in the shape of a human body or the body of another animal. In some embodiments, the hydrogel phantom 78 is formed to be an anatomically accurate representation of a particular human or other animal or a part thereof.

[0039] Referring to Figure 3A, which is shown therein is a cross-sectional diagram of an exemplary embodiment of the hydrogel phantom 78 of Figure 2, depicted as a hydrogel phantom head 100 (phantom head 100) formed from a plurality of hydrogel elements 82a-n. In the example shown, the hydrogel phantom head 100 is formed from a skin hydrogel element 82c, a bone hydrogel element 82d, and a brain hydrogel element 82e. The phantom head 100 shown in Figure 3A is depicted for simplicity only as containing three hydrogel elements 82a-n, and can also contain any number of hydrogel elements 82a-n required by the user to appropriately model the electrical conductivity of a selected part of a human or non-human body. Also shown in Figure 3A are a first electric field generating pad 70a and a second electric field generating pad 70b on the outer surface 84 of the phantom head 100.

[0040] Therefore, in some embodiments, in order to appropriately model the electrical conductivity of the selected biological component, the user should first determine the desired frequency (or frequency range) of the signal to be tested, and thus, a suitable conductivity can be selected with respect to the hydrogel phantom 78 to best match the conductivity of the selected biological component. The user can select one or more conductivity values ​​from the conductivity of biological components known in the art, such as, for example, S. Gabriel, in The Dielectric Properties of Biological Tissues: II Measurements in the frequency range of 10 Hz to 20 GHz (S. Gabriel et al. 1996 Phys. Med. Biol. 41 2251).

[0041] In other embodiments, the user can select the average conductivity for one or more biological components, as calculated by Ramon et al. (Ramon C, Gargiulo P, Frigeirsson EA and Haueisen J (2014) Changes in Scalp Potentials and Spatial Smoothing Effects of Inclusion of Dura Layer in Human Head Models for EEG Simulations. Front. Neuroeng. 7:32. doi:10.3389 / fneng. 2014.00032). As just one example, and as calculated by Ramon, the user can select 1.35E-3 S / cm as the average conductivity for the skin hydrogel element 82c, 6.25E-5 S / cm as the average conductivity for the bone hydrogel element 82d, and 3.334E-3 S / cm as the average conductivity for the brain hydrogel element 82e.

[0042] In some embodiments, the hydrogel phantom 78 includes one or more support structures (not shown) for providing support to the hydrogel phantom 78. Each of the one or more support structures can be nonconductive, electrically isolated, or both. In one embodiment, the one or more support structures are selected to cause minimal interference with the generated TTField.

[0043] While the exemplary embodiment of the hydrogel phantom 78 in Figure 2 is depicted as an ultra-accurate representation of a human head, it should be noted that in some embodiments, the hydrogel phantom 78 can also be formed from the minimum number of hydrogel elements 82a-n required to model the electric field target 74 for a desired purpose.

[0044] By generating a hydrogel phantom 78, the user can determine the actual values ​​and shapes of the TTFfield in and / or around the hydrogel phantom 78 resulting from the application of an alternating electric field. For example, by utilizing one or more sensors 102a~n (discussed in more detail below), the user can determine magnetic properties (e.g., one or more electric or electromagnetic field power / intensity); electrical properties (e.g., voltage, current, inductance, capacitance); thermal properties (e.g., temperature); or pressure; force; and / or similar properties at various locations within the hydrogel phantom 78. The determined actual values ​​can be recorded for various configurations of the hydrogel phantom 78 and made available to the user to generate or improve computer simulations. If the hydrogel phantom 78 represents a particular patient, the determined actual values ​​can be used to improve or increase the therapeutic benefits of TTField therapy for that particular patient. Furthermore, by applying an alternating current electric field to the hydrogel phantom 78, users can understand how an alternating current electric field (e.g., TTField) travels through human or non-human bodies and around various types of tissues and / or bones in an accurate, non-computer-simulation-based setting.

[0045] In one embodiment, the hydrogel phantom 78 is a polymerized gel (in solid form) and comprises two or more hydrogel elements 82a-n, which are polymerized gels having a bulk electron transporter that provides a source of free ions within them to allow electrical conductivity to result in volume resistivity. In one embodiment, each hydrogel element 82a-n is formed from a conductive gel or a semi-solid conductive gel.

[0046] In the embodiment depicted in Figure 3A, the phantom head 100 includes three hydrogel elements 82: a skin hydrogel element 82c, a bone hydrogel element 82d, and a brain hydrogel element 82e, each of which is bonded to at least a portion of another hydrogel element 82. The skin hydrogel element 82c includes the shape, thickness, and volume of human skin and also includes substantially uniform electrical resistance / impedance / conductivity that mimics the electrical resistance / impedance / conductivity of human skin. The bone hydrogel element 82d is positioned within the hydrogel phantom 78 in a manner that mimics the location of bone in a human head. The bone hydrogel element 82d includes the shape, thickness, and volume of human bone in a human head and may also include substantially uniform electrical resistance / impedance / conductivity that mimics the electrical conductivity of human bone. The bone hydrogel element 82d is adjacent to the skin hydrogel element 82c and defines the boundary of the skin hydrogel element 82c. The brain hydrogel element 82e includes the shape, thickness, and volume of a human brain. The brain hydrogel element 82e can contain substantially uniform electrical resistance / impedance / conductivity that mimics the electrical resistance / impedance / conductivity of a human brain. The brain hydrogel element 82e is partially surrounded by the bone hydrogel element 82d, which defines the boundary of the bone hydrogel element 82d.

[0047] Although the hydrogel phantom 78 is described as having three different types of hydrogel elements (i.e., skin hydrogel element 82c, bone hydrogel element 82d, and brain hydrogel element 82e), the hydrogel phantom 78 can be provided with other types of hydrogel elements (e.g., vascular hydrogel elements, cerebrospinal fluid hydrogel elements, blood hydrogel elements, or tumor hydrogel elements). In some embodiments, the hydrogel elements 82 are connected together to form a continuous hydrogel device having regions of varying electrical resistance / conductivity, and are designed to collectively mimic the electrical resistance / impedance / conductivity of the human head.

[0048] In one embodiment, each hydrogel element 82a-n is primarily formed from a conductive gel or a semi-solid conductive gel, as described below, for example. The hydrogel elements 82a-n taught herein can be used with modified hydrogels (which include not only perforations but also recesses, protrusions, etc.) as disclosed in detail in U.S. Patent Application No. 63 / 020,636, titled "Conductive Gel Compositions Comprising Bulk Electron Transport Agents and Methods of Production and Use Thereof," which is incorporated herein in its entirety.

[0049] The conductive gel can be in any form that enables the composition to function in accordance with this disclosure. For example (but not limited to), each hydrogel element 82a-n can be in the form of a hydrogel or a hydrocolloid.

[0050] In one embodiment, each hydrogel element 82a-n can be formed from two or more constituent hydrogels. Each constituent hydrogel is a conductive gel having one or more structural water-soluble polymers, one or more crosslinking agents, one or more photoinitiators, one or more electrolytes, and one or more additives.

[0051] The conductive gels can be formed from any hydrophilic polymer that enables each of the constituent hydrogels of each hydrogel element 82a-n to function in accordance with this disclosure. For example (but not limited to), one or more of the conductive gels can be polyacrylic acid gels, povidone gels, or cellulose gels. In addition, one or more conductive gels can include at least one of chitosan, alginates, agarose, methylcellulose, hyaluronic acid, collagen, laminin, Matrigel, fibronectin, vitronectin, poly-1-lysine, proteoglycans, fibrin glue, gels made by decellularization of artificial and / or natural tissues, and any combination thereof. Furthermore, one or more conductive gels may contain at least one of the following: polyglycolic acid (PGA), polylactic acid (PLA), polycaprolactone (PCL), polyvinyl alcohol (PVA), polyethylene glycol (PEG), methyl methacrylate, poly(methyl methacrylate) (PMMA), poly(2-hydroxyethyl methacrylate) (PolyHEMA), poly(glycerol sebacate), polyurethane, poly(isopropylacrylamide), poly(N-isopropylacrylamide), or any combination thereof.

[0052] In certain non-limiting embodiments, the conductive gel comprises one or more of the following chemical and structural features / properties: polymer chain length in the range of about 1 nm to about 200 nm; free salts present at concentrations in the range of about 0.1 mM to about 1 M; pH in the range of about 6 pH to about 8 pH; and volume resistivity of less than about 100 Ohm-in.

[0053] The polymer for the conductive gel can be provided having any polymer chain length that enables the conductive gel composition to function as described herein. For example (but not limited to), the polymer chain length can be in the range of about 3 nm to about 175 nm, in the range of about 5 nm to about 150 nm, or in the range of about 10 nm to about 125 nm, in the range of about 15 nm to about 100 nm, and in the range of a combination of two integers that fall between two of the above values ​​(i.e., in the range of about 3 nm to about 157 nm).

[0054] In some embodiments, the constituent hydrogel comprises one or more electrolytes (for example, purified water electrolyte or free salt).

[0055] In one embodiment, each hydrogel element 82a-n can be formed from two or more components. Each component can include one or more structural water-soluble polymers, one or more crosslinking agents, one or more photoinitiators, one or more electrolytes, and one or more additives. In one embodiment, one or more additives in each component can include one or more humectants and / or preservatives.

[0056] In one embodiment, each component comprises one or more crosslinkers and one or more photoinitiators. The crosslinkers are structural polymers, which provide stabilization of the hydrogel and, when activated, lead to multidimensional elongation of the polymer chains. The photoinitiators are specific crosslinkers, which, during the curing of the hydrogel, activate one or more crosslinkers, thereby causing one or more crosslinkers to form multidimensional elongation of the polymer chains of the structural polymer, and thus form a three-dimensional (3D) gel. Crosslinking can be formed by double bonds or functional groups in the structural polymer.

[0057] The curing of a hydrogel is the polymerization of the hydrogel, which can be constructed by a combination of two or more components, generally by applying a curing agent. Prior to polymerization, the hydrogel can be a liquid hydrogel. In one embodiment, polymerization can be achieved by applying UV irradiation of a certain amount to the hydrogel. The amount of UV irradiation can include the duration and intensity of the irradiation and can be determined based on user requirements (e.g., the degree of crosslinking) that affect the tackiness and conductivity of the hydrogel. That is, by adjusting the amount of UV irradiation (e.g., the duration and / or intensity of the UV irradiation), the user can adjust the curing properties of the hydrogel (e.g., the conductivity and tackiness of the hydrogel). In another embodiment, polymerization can be achieved by applying an alternative form of energy (e.g., an electron beam or laser) to cure the hydrogel. Applying an electron beam or laser to the hydrogel can result in high crosslinking rates and efficiency. The duration of electron beam or laser application, and the intensity of electron beam or laser application, can be modified to adjust the curing properties of the hydrogel.

[0058] In one embodiment, specific components for forming a hydrogel, and / or curing the hydrogel, are used to provide desired curing properties to each of the multiple hydrogel elements 82a to n.

[0059] For example, in the laboratory experiments summarized in Table 1 below, a UV-curable hydrogel (product number #JN0917-A) obtained from Polychem UV / EB International Corp. in Taipei, Taiwan was used. This UV-curable hydrogel contains two components (referred to as the first and second components). The first and second components were mixed together in three different ratios, resulting in a first experimental hydrogel element, a second experimental hydrogel element, and a third experimental hydrogel element. For each experimental hydrogel element, the volume resistivity value was calculated over a varying hydrogel curing duration while curing with a UV LED providing light at a wavelength of 365 nm.

[0060] The first experimental hydrogel element was composed of a first component and a second component in a ratio of 1:0.3. The volume resistivity was determined to be 2909ρ (Ω / cm) after a hydrogel curing period of 10 minutes; 2909ρ (Ω / cm) after a hydrogel curing period of 20 minutes; and 4160ρ (Ω / cm) after a hydrogel curing period of 40 minutes.

[0061] The second experimental hydrogel element was composed of the first and second components in a ratio of 1:0.65. The volume resistivity was determined to be 272ρ (Ω / cm²) after a hydrogel curing duration of 10 minutes; 356ρ (Ω / cm²) after a hydrogel curing duration of 20 minutes; and 364ρ (Ω / cm²) after a hydrogel curing duration of 40 minutes. The second experimental hydrogel element is POLYCHEM Advanced UV Curable Conductive #JN0917-A, a fully synthetic polyacrylamide-based and chemically crosslinked high-performance hydrogel containing purified water, a humectant, and a fully synthetic photopolymer. The second experimental hydrogel element had a liquid viscosity of 150±50 cps and a pH between 4.0 and 7.0 at 25°C.

[0062] The third experimental hydrogel element was composed of the first and second constituent hydrogels in a ratio of 1:0.9. After a 10-minute hydrogel curing period, the third experimental hydrogel element still remained in an almost liquid state and required an additional 5-minute hydrogel curing period, at which point the volume resistivity was determined to be 86ρ (Ω / cm); after a 25-minute hydrogel curing period, the volume resistivity was determined to be 104ρ (Ω / cm); and after a 45-minute hydrogel curing period, the volume resistivity was determined to be 104ρ (Ω / cm).

[0063] [Table 1]

[0064] Referring again to Figure 3A, each of the skin hydrogel element 82c, bone hydrogel element 82d, and brain hydrogel element 82e can be composed of the same or different ratios of first and second components as another hydrogel element 82. For example, the skin hydrogel element 82c can be composed of first and second components in a first ratio that results in a first volume resistivity, the bone hydrogel element 82d can be composed of first and second components in a second ratio that results in a second volume resistivity, and the brain hydrogel element 82e can be composed of first and second components in a third ratio that results in a third volume resistivity, where the first, second, and third ratios may be the same or different, and the first, second, and third volume resistivity may be the same or different. In one embodiment, one or more of the skin hydrogel element 82c, bone hydrogel element 82d, and brain hydrogel element 82e may be partially composed of additional components different from the first and / or second components.

[0065] In one embodiment, a user can construct a phantom head 100 that is electrically similar to a human head (e.g., a patient's head). That is, a user can construct a phantom head 100 such that the volume resistivity of the skin hydrogel element 82c is similar to that of a patient's skin in terms of volume resistivity, the volume resistivity of the bone hydrogel element 82d is similar to that of the bone of a patient's skull in terms of volume resistivity, and the brain hydrogel element 82e is similar to that of a patient's brain in terms of volume resistivity. In one embodiment, a user can also construct a phantom head 100 that includes a target hydrogel element 82f having a volume resistivity similar to that of a target (e.g., a target tumor) in terms of resistivity.

[0066] In one embodiment, the user can construct the phantom head 100 to include one or more additional hydrogel elements 82a-n that model the volume resistivity of other components in or around the patient's head (e.g., cartilage, eyes, hair, mucus, saliva, and nerves). In one embodiment, the user can construct one or more hydrogel elements 82a-n to simulate a portion of an organ; for example, the user can construct a first brain hydrogel element that is similar to the gray matter of the brain in terms of volume resistivity, and a second brain hydrogel element that is similar to the white matter of the brain in terms of volume resistivity; or the user can construct a first bone hydrogel element that is similar to bone marrow in terms of volume resistivity, a second bone hydrogel element that is similar to cancellous bone in terms of volume resistivity, and a third bone hydrogel element that is similar to compact bone in terms of volume resistivity.

[0067] In one embodiment, the phantom head 100 may have one or more sensors 102a-n, each having sensor leads 104a-n and associated with a specific location on or within the phantom head 100, where the sensors 102a-n are, for example, a first sensor 102a and a second sensor 102b, where the first sensor 102a has a sensor lead 104a and is associated with a target hydrogel element 82f, and the second sensor 102b has a sensor lead 104b and is associated with a skin hydrogel element 82c. Additionally, each electric field generating pad 70 (for example, a first electric field generating pad 70a and a second electric field generating pad 70b) may include one or more sensors 102a-n. Each of the sensors 102a-n may include one or more of the following: electric field sensors, voltage sensors, ampere sensors, temperature sensors, and / or electromagnetic field sensors. In one embodiment, by monitoring each of the sensors 102a-n, the user can determine the optimal placement of each of the one or more electric field generating pads 70. The optimal placement of each of the one or more electric field generating pads 70 can be determined by receiving data from the sensors 102a-n that shows the maximized therapeutic benefit of the TTField generated when one or more TTF signals are supplied to the first electric field generating pad 70a, the second electric field generating pad 70b, and any other electric field generating pads 70 that will be applied to the hydrogel phantom 78.

[0068] In some embodiments, one or more sensors 102a-n can be placed at multiple different locations throughout the phantom hydrogel 78. For example, sensor 102c is placed in the anterior region of the brain hydrogel element 82c. By placing one or more sensors 102a-n throughout the hydrogel phantom 78, a user can determine the characteristics of the alternating electric field (e.g., TTField) at multiple locations within the phantom hydrogel 78. In other embodiments, at least one of the one or more sensors 102a-n can be placed at the intersection between two or more hydrogel elements 82a-n. By placing sensor 102 at the intersection between two or more hydrogel elements 82a-n, a user can determine one or more characteristics of the alternating electric field as it passes from the first hydrogel element 82 to the second hydrogel element 82.

[0069] In some embodiments, each of one or more sensors 102a-n includes sensor leads 104a-n that are communicatively coupled to an external device 120. By accessing the external device 120, a user may be able to determine values ​​relating to one or more characteristics of each sensor 102a-n. However, in other embodiments, each of one or more sensors 102a-n may not include sensor leads 104a-n but may include a wireless transceiver, which is communicatively coupled to the external device 120 using a wireless communication topology that meets the requirements of Bluetooth, RFID, WIFI, Xbee, and Z-wave, or some combination thereof, or any other wireless communication topology. In some embodiments, sensor 102 includes a sensor coupled to a processor through an analog-to-digital converter to provide a digital signal that can be read and interpreted by the processor. In these embodiments, one sensor lead may couple the processor to the wireless transceiver, allowing the processor to transfer data and instructions to the external device 120 via the wireless transceiver.

[0070] In one embodiment, the phantom head 100 may have one or more simulated veins 108a-n. While one or more simulated veins 108a-n are referred to as veins, one or more simulated veins 108a-n may also simulate arteries or other parts of the human body designed to carry or transport a model fluid. In one embodiment, each of the one or more simulated veins 108a-n may include a tube or hose, etc., that can operate to circulate a model fluid (e.g., blood, or synthetic blood having electrical conductivity and / or volume resistivity properties similar to human blood) within the phantom head 100. In one embodiment, the synthetic blood also has thermal conductivity properties similar to human blood. In one embodiment, the model fluid is circulated while receiving data from one or more sensors 102a-n.

[0071] In one embodiment, the hydrogel phantom 78 can be constructed to include one or more non-gel elements 112 (e.g., medical devices or one or more simulated veins 108a-n). For example, if the hydrogel phantom 78 is a phantom head 100, the user can construct the phantom head 100 to include one or more non-gel elements 112 (e.g., medical devices including metal plates such as bone-fixed hearing aids, cochlear implants, and / or those used to close skull defects). By constructing the hydrogel phantom 78 to include one or more non-gel elements 112, the user can measure changes in the electric field (e.g., TTField) within the hydrogel phantom 78 due to one or more non-gel elements 112.

[0072] In some embodiments, one or more non-gel elements 112 actively generate an electric field as a medical device (e.g., a pacemaker). In one embodiment, by constructing a hydrogel phantom 78 as a thoracic cavity having one or more hydrogel elements 82a~n having similar volume resistivity to various organs in the thoracic cavity, and by including a pacemaker within the hydrogel phantom 78, a user can measure the electric field caused by the electric field generating pads 70a~n and any fluctuations in the electric field caused by electrical signals generated by the pacemaker.

[0073] In one embodiment, one or more additional electric field generating pads 70 (not shown) can be attached to the phantom head 100. A generator 54 connected to each electric field generating pad 70 can supply a first electrical signal having a first power and a first frequency to a first group of one or more electric field generating pads 70 (e.g., a first electric field generating pad 70a and a second electric field generating pad 70b), and can also supply a second electrical signal having a second power and a second frequency to a second group of one or more electric field generating pads 70 attached to the phantom head 100 in the same instance in time. That is, the generator 54 can supply the first electrical signal to the first group and the second electrical signal to the second group simultaneously. Although the above embodiment describes only the first and second groups, it will be understood that there can be three or more groups.

[0074] Figure 3B is a cross-sectional diagram of another exemplary embodiment of the hydrogel phantom 78 of Figure 2, depicted as a fluid container 130 configured to appropriately model the electrical conductivity of the external and internal components of the biological components. The fluid container 130 can be any shape, including, but is not limited to, a cube, a rectangular prism, a sphere, a cone, a cylinder, or any hypothetical shape. The fluid container 130 shown in Figure 3B is a concave, nearly hemispherical container formed to hold the fluid.

[0075] The fluid container 130 includes at least one external wall portion 134 having an external surface 136 and an internal surface 138. The at least one external wall portion 134 can be formed from at least one hydrogel element 82. In some embodiments, the fluid container 130 includes a single wall portion formed from a first hydrogel element 82g. The hydrogel element 82g can be configured to approximate and / or model the electrical conductivity of external components of biological components (e.g., skull, external skin of the torso, and combinations thereof). For example, the hydrogel element 82g can be configured to approximate and / or model the electrical conductivity of the skull of a human or non-human body. To that end, the hydrogel element 82g can be configured to approximate and / or model the electrical conductivity of bone, skin, and / or brain material.

[0076] The interior of the fluid container 130 can be filled or partially filled with a fluid solution 140. The fluid solution 140 can be configured to approximate and / or model the electrical conductivity inside biological components (e.g., brain material, blood, organs). For example, the fluid solution 140 can be configured to approximate and / or model the electrical conductivity of brain material (i.e., white matter and / or gray matter). In some embodiments, the fluid solution 140 can be configured to approximate, for example, the average conductivity of white matter and gray matter. In some embodiments, the fluid solution 140 can be a saline solution, and the salt content of the saline solution is configured to approximate the electrical conductivity inside biological components.

[0077] Referring to Figure 3B, in some embodiments, one or more target hydrogel elements 82f can be formed on or attached to at least a portion of one movable probe 142. The target hydrogel elements 82f can be configured to have a resistivity approximating one or more target tumors. The target hydrogel elements 82f can be positioned at any point on the movable probe 142. At least one movable probe 142 (having a target hydrogel element 82f formed on or attached thereto) can be positioned around the interior of the fluid container 130 and can move within the fluid solution 140 of the fluid container 130. For example, at least one movable probe 142 can be positioned at a first location inside the fluid container 130, where one or more measurements can be taken against the target hydrogel element 82f. Next, at least one movable probe 142 can be positioned in a second location within the fluid container 130, where one or more measurements can be taken for a target hydrogel element 82f. Additionally, one or more target hydrogel elements 82f can be used in conjunction with at least one movable probe 142. For this purpose, at least one movable probe 142 can be positioned in a first location, where one or more measurements can be taken for a first target hydrogel element 82f attached to the probe 142. At least one movable probe 142 can be positioned in a second location, where one or more measurements can be taken for a second target hydrogel element 82f attached to the probe 142. It should be noted that additional probes (movable or stationary) can be positioned within the fluid container 130 in accordance with this disclosure.

[0078] In some embodiments, the fluid container 130 may include one or more sensors 102a-n (shown in Figure 3A), one or more simulated veins 108a-n (shown in Figure 3A), and / or one or more non-gel elements 112 (shown in Figure 3A), positioned inside the fluid container 130 (for example, in the fluid solution 140 of the fluid container 130), similar to the phantom head 100.

[0079] At least one movable probe 142 can be configured to be positioned inside the fluid container 130 to measure the electric field inside the fluid container 130. The interior of the fluid container 130 is bounded by the interior surface 138 of the outer wall 134. Referring to Figures 2 and 3B, one or more electric field generating pads 70 can be attached to the exterior surface 136 of the outer wall 134 of the fluid container 130. A generator 54 connected to each electric field generating pad 70 can supply a first electrical signal having a first power and a first frequency to a first group of one or more electric field generating pads 70 (e.g., a first electric field generating pad 70a and a second electric field generating pad 70b), and can also supply a second electrical signal having a second power and a second frequency to a second group of one or more electric field generating pads 70 attached outside the fluid container 130. At least one movable probe 142 (having at least one target hydrogel element 82f on or attached thereto) can be configured to measure the electric field in the internal fluid container 130 and, in some embodiments, the electric field in the target hydrogel element 82f during the generation of an electrical signal from the generator 54.

[0080] Referring here to Figure 4A, which shows a diagram of an exemplary embodiment of a gel dispensing system 200 constructed in accordance with the present disclosure. The gel dispensing system 200 generally includes one or more applicators 204 and a platform 208 movably mounted to a housing 212. Only one applicator 204 is shown for the purpose of simplification, however, two or more applicators 204 may also be utilized. One or more applicators 204 further include at least a nozzle 216 for dispensing a conductive gel (described in more detail above) at a predetermined discharge rate. The platform 208 supports the hydrogel phantom 78 (depicted as a partial phantom head 100' having partial skin hydrogel elements 82c' and partial bone hydrogel elements 82d') while the hydrogel phantom 78 is being constructed. In one embodiment, the first and second components (in liquid form) can be mixed in an applicator 204 and discharged as a liquid conductive gel from a nozzle 216 of the applicator 204.

[0081] In one embodiment, the applicator 204 is capable of moving in one of the following directions: a first direction 220, a second direction 224, or a third direction 226, or a combination thereof. In one embodiment, the platform 208 is capable of moving in the first direction 220, a second direction 224, a third direction 226, or a combination thereof. The first direction 220 can be the y-direction, the second direction 224 can be the x-direction, and the third direction 226 can be the z-direction. In one embodiment, the gel dispensing system 200 includes a controller 228 to control the movement of the platform 208 and / or the movement of the applicator 204.

[0082] In some embodiments, the controller 228 is loaded with a three-dimensional model of a proposed hydrogel phantom having at least one proposed hydrogel element. In these embodiments, the three-dimensional model provides a plurality of voxels, each voxel being a portion of one of the at least one proposed hydrogel element. Each voxel is provided with characteristic information that identifies (or is used to determine) a specific resistance, impedance, or conductance for the voxel. The characteristic information can be read by the controller 228 and used to generate a voxel having resistance, impedance, or conductance.

[0083] In one embodiment, the controller 228 may be provided with a memory 229 (e.g., a non-temporary computer-readable medium) communicably coupled to a circuit, for example, at least one processor 230. The memory 229, which stores the three-dimensional model and computer-executable code configured to read the three-dimensional model, may be accessed by the processor 230. The processor 230 (executing the computer-executable code configured to read the three-dimensional model) may cause the applicator 204 (of the platform 208) to move in one or more of the first direction 220, the second direction 224, or the third direction 228, causing the applicator 204 to release the conductive gel at a predetermined release rate. In one embodiment, a computer system (not shown) is used to model the hydrogel phantom 78 as a plurality of voxels of the three-dimensional model and to communicate the three-dimensional model to the controller 228, where the three-dimensional model may then be stored in the memory 229. In one embodiment, the controller 228 communicates with one or more computer systems and receives a three-dimensional model or a plurality of voxels forming a three-dimensional model.

[0084] In one embodiment, the gel application system 200 further includes a curing device 232 that causes the first and second components (in liquid form) to cure (or polymerize) to become a three-dimensional conductive gel of one or more hydrogel elements 82. The curing device 232 is capable of supplying a curing agent (e.g., UV radiation, laser, and / or electron beam) to a particular voxel 234, for example, containing the first and second components (in liquid form), where the particular voxel 234 is an uncured voxel in a three-dimensional model corresponding to a particular one of the one or more hydrogel elements 82, as shown in Figure 4A as a partial skin hydrogel element 82c' or a partial bone hydrogel element 82d'. Thereafter, the curing device 232, by applying the curing agent, causes the particular voxel 234 to polymerize to become a three-dimensional conductive gel that forms a portion of a particular one of the one or more hydrogel elements 82.

[0085] In one embodiment, the user uses the controller 228 to cause the applicator 204 of the gel application system 200 to release a first liquid hydrogel composed of a first component and a second component having a first ratio, and to cause the curing device 232 to supply a curing agent to the first liquid hydrogel at a first intensity over a first duration to form a first voxel of a partial skin hydrogel element 82c' having a volume resistivity similar to that of the patient's skin, and to cause the applicator 204 of the gel application system 200 to release a second liquid hydrogel composed of a first component and a second component having a second ratio, and to cause the curing device 232 to supply a curing agent to the second liquid hydrogel at a second intensity over a second duration to form a second voxel of a partial bone hydrogel element 82d' having a volume resistivity similar to that of the patient's skull.

[0086] In one embodiment, the user uses a controller 228 to cause the applicator 204 of the gel application system 200 to release a liquid hydrogel composed of a first component and a second component having a specific ratio, and the curing device 232 supplies a curing agent to the liquid hydrogel at a specific intensity over a specific duration on a per-voxel basis (i.e., with respect to a particular voxel), for example, with respect to each portion of at least one hydrogel element 82, the applicator 204 releases the liquid hydrogel, and after the liquid hydrogel for a particular voxel has been released, the curing device 232 supplies a curing agent to the released liquid hydrogel. In one embodiment, the volume of each voxel can be determined based on one or more of the following: the precision required when forming the hydrogel phantom 78, the volume of liquid hydrogel that can be cured in each voxel based (partially) on the viscosity of the liquid hydrogel, and the penetration limit of the curing agent into the liquid hydrogel in the voxel. In one embodiment, each voxel of each hydrogel element 82 has a similar volume. In some embodiments, each voxel is 0.001 mm 3 1cm 3 It has a volume between [a certain range]. In some embodiments, each voxel has approximately the same volume, while in other embodiments, not all voxels have the same volume. In some embodiments, each voxel has a width between 0.01 mm and 1 cm.

[0087] In one embodiment, the controller 228 is capable of slicing a three-dimensional model into one or more layers, where each layer is a plurality of substantially coplanar voxels, and each voxel of the plurality of substantially coplanar voxels corresponds to a volume of a particular hydrogel element 82a-n. With respect to each voxel on a particular layer, the controller 228 is capable of causing the applicator 204 to release liquid hydrogel (composed of at least a first and a second component), and also applying a curing agent to the voxel so that the voxel exhibits electrical conductivity, impedance, and / or volume resistivity similar to the corresponding volume of the voxel of the particular hydrogel element 82a-n. In one embodiment, the controller 228 causes all or most of the substantially coplanar voxels to be released and cured on a layer-by-layer basis, i.e., when the controller 228 slices a three-dimensional model into a first layer having a first plurality of substantially coplanar voxels and a second layer having a second plurality of substantially coplanar voxels, the controller 228 can cause most or all of the first plurality of substantially coplanar voxels to be formed in the first layer before causing most or all of the second plurality of substantially coplanar voxels in the second layer to be formed. In one embodiment, the computer system is capable of slicing a three-dimensional model into one or more layers, where each layer is a plurality of substantially coplanar voxels, and each voxel of the plurality of substantially coplanar voxels corresponds to a volume of a particular hydrogel element 82a~n.

[0088] In one embodiment, the nozzle 216 has a dispensing distance determined by the distance between the nozzle 216 and the platform 208, and dispenses a conductive gel (e.g., hydrogel, etc.) (in liquid form) at a predetermined dispensing pressure and moves relative to the platform 208 at a predetermined dispensing speed. By adjusting the dispensing distance, dispensing pressure, and dispensing speed, the voxel volume and / or voxel shape can be adjusted.

[0089] In one embodiment, two or more applicators 204 are used, making it possible to form two or more hydrogel phantoms 78 simultaneously.

[0090] In one embodiment, while a partial phantom head 100' is being constructed (or printed) by a gel application system 200, one or more non-gel elements (e.g., one or more medical devices and / or one or more simulated veins 108a-n, etc.) can be placed on a specific layer of the partial phantom head 100'. By attaching one or more non-gel elements during the construction of the phantom head 100, the conductive gel can adhere to the non-gel elements as the conductive gel hardens, thereby preventing the movement of one or more non-gel elements. This is because the movement of the non-gel elements could introduce an error into the hydrogel phantom 78.

[0091] Referring now to Figure 4B, which is shown therein is a diagram of an exemplary embodiment of a gel dispensing system 200a constructed in accordance with the present disclosure. The applicator 204 comprises a first applicator 204a and a second applicator 204b, the first applicator 204a being operable to discharge a first component (in liquid form) at a first velocity through a first nozzle 216a, and the second applicator 204b being operable to discharge a second component (in liquid form) at a second velocity through a second nozzle 216b, and the gel dispensing system 200a is similar in construction and function to the gel dispensing system 200 described above and shown in Figure 4A, except that the first and second components mix to form one portion of the hydrogel element 82. In this embodiment, by adjusting the first release rate of the first component and the second release rate of the second component over a predetermined period of time, the user can select a ratio between the first component and the second component so that they solidify into a solid gel form. By repeating the steps of applying the first and second components and then curing the applied first and second components, the gel application system 200 can generate the hydrogel elements 82a-n of the hydrogel phantom 78.

[0092] The gel application system 200a further includes a platform 208 that is movably mounted on the housing 212. The platform 208 supports the hydrogel phantom 78 while it is being constructed. The hydrogel phantom 78 is depicted as a partial phantom head 100' having a partial skin hydrogel element 82c' and a partial bone hydrogel element 82d'.

[0093] In some embodiments, the controller 228 is loaded with a three-dimensional model of a proposed hydrogel phantom having at least one proposed hydrogel element. In these embodiments, the three-dimensional model provides a plurality of voxels, each voxel being a portion of one of the at least one proposed hydrogel element. Each voxel is provided with characteristic information that identifies (or is used to determine) a specific resistance, impedance, or conductance for the voxel. The characteristic information can be read by the controller 228 and used to generate voxels having resistance, impedance, or conductance. The controller 228 can be provided with a memory 229 (e.g., a non-temporary computer-readable medium) that is communicably coupled to at least one processor 230. The memory 229, which stores the three-dimensional model and computer-executable code configured to read the three-dimensional model, can be accessed by the processor 230. Processor 230 (which executes computer-executable code configured to read a three-dimensional model) can cause the first applicator 204a and the second applicator 204b (of platform 208) to move in one or more of the first direction 220, the second direction 224, or the third direction 228, and can cause the first applicator 204a to discharge the first component (in liquid form) at a first velocity through the first nozzle 216a, and the second applicator 204b can operate to discharge the second component (in liquid form) at a second velocity through the second nozzle 216b.

[0094] In one embodiment, a computer system (not shown) is used to model the hydrogel phantom 78 as a plurality of voxels in a three-dimensional model, and is also used to communicate the three-dimensional model to a controller 228, in which the three-dimensional model can then be stored in memory 229. In one embodiment, the controller 228 communicates with one or more computer systems and receives a three-dimensional model or a plurality of voxels forming the three-dimensional model. In one embodiment, the computer system can slice the three-dimensional model into one or more layers, where each layer is a plurality of substantially coplanar voxels, and each voxel of the plurality of substantially coplanar voxels corresponds to a volume of a particular hydrogel element 82a-n.

[0095] Referring now to Figure 5, which shows an exemplary embodiment of the hydrogel phantom formation process 250, the hydrogel phantom formation process 250 generally includes the steps of determining a desired volume resistivity (step 254), combining a first volume of first component hydrogel and a second volume of second hydrogel to form a hydrogel element (step 258), and curing the hydrogel element to form a hydrogel phantom (step 262).

[0096] In one embodiment, the step of determining a desired volume resistivity (step 254) can be carried out by measuring the volume resistivity of a target area of ​​the patient (e.g., a target tumor). In one embodiment, the step of determining a desired volume resistivity (step 254) can include the step of selecting a volume resistivity for a specific part of the patient (e.g., a specific organ) with respect to a predetermined set of electrical conductivity for that specific organ. For example, if the specific organ is the liver, and it is predetermined that the liver generally has a predetermined liver volume resistivity, then the predetermined liver volume resistivity can be selected as the desired volume resistivity.

[0097] In one embodiment, the step of combining a first component of a first volume and a second component of a second volume to form a hydrogel element (step 258) generally includes the step of selecting a hydrogel component ratio such that it is determined to produce, for example, Table 1, where the particular ratio includes a volume resistivity that approximates or is similar to a desired volume resistivity, and the step of selecting the first volume and the second volume such that the ratio of the first volume to the second volume is approximately equal to the hydrogel component ratio.

[0098] In one embodiment, the step of combining a first component of a first volume and a second component of a second volume to form a hydrogel element (step 258) may further include the step of forming one or more voxels having a first volume of the first component and a second volume of the second component, where each voxel is a discrete volume or portion of the hydrogel element.

[0099] In one embodiment, the step of curing the hydrogel element to form a hydrogel phantom (step 262) generally includes the step of applying a curing agent to the hydrogel element over a specific duration. For example, the specific duration can be determined based on a portion of the curing duration corresponding to the hydrogel component ratio with respect to a desired volume resistivity. In one embodiment, the step of curing the hydrogel element to form a hydrogel phantom (step 262) can include curing each of one or more voxels as each voxel is formed, such that the cured and solidified voxels collectively form the hydrogel element.

[0100] Referring now to Figure 6, which shows an exemplary embodiment of the electric field generating pad location setting process 300, the electric field generating pad location setting process 300 generally includes the steps of: attaching two or more electric field generating pads to the hydrogel phantom 78 at specific locations (step 304); generating an alternating electric field having a frequency in the range of about 50 kHz to about 1 MHz for a predetermined period of time (step 308); measuring one or more sensors to determine effectiveness (step 312); determining whether the effectiveness exceeds an effectiveness threshold (step 316); selecting each of the two or more electric field generating pads on the hydrogel phantom at specific locations as therapeutic electric field generating pad locations if the effectiveness exceeds the effectiveness threshold (step 320); otherwise, returning to step 304.

[0101] In one embodiment, the step of attaching two or more electric field generating pads to the hydrogel phantom (step 304) can be performed by a user and may include the steps of attaching two or more electric field generating pads to specific locations on the hydrogel phantom 78 and attaching one or more sensors to the hydrogel phantom 78. In one embodiment, the step of generating an alternating electric field having a frequency in the range of about 50 kHz to about 500 kHz over a predetermined period of time (step 308) may be performed by a user and include the steps of accessing the generator 54 or the control box 86 and causing the generator 54 to generate an alternating electric field.

[0102] In some embodiments, the step of measuring one or more sensors to determine effectiveness (step 312) may include measuring electric field strength or intensity, measuring voltage, measuring amperage, or measuring temperature, or some combination thereof, with respect to one or more sensors 102a-n attached to the hydrogel phantom 78, in order to determine the effectiveness of the applied AC electric field in the target region. In one embodiment, the applied AC electric field is the TTField, and the target region is the target region of the electric field target 74. In some embodiments, the step of measuring to determine effectiveness may include obtaining one or more measurements of the electric field from the movable probe 142.

[0103] In one embodiment, the step of determining whether the effectiveness threshold is exceeded (step 316) includes comparing the effectiveness, as determined in step 312, to the effectiveness threshold, and if it is exceeded, selecting each of the current locations of the two or more electric field generating pads 70 on the hydrogel phantom 78 as therapeutic electric field generating pad locations. If the effectiveness is below the effectiveness threshold, the step of attaching the two or more electric field generating pads to the hydrogel phantom 78 (step 304) is repeated, and the two or more electric field generating pads are attached to the hydrogel phantom at locations different from at least one of the specific locations. For example, if the effectiveness threshold is a temperature threshold, the step of determining whether the effectiveness is below the effectiveness threshold (step 316) includes comparing the effectiveness, as determined by measuring the temperature, to the temperature threshold, and if the temperature is above the temperature threshold, the step of continuing to select each of the specific locations of the two or more electric field generating pads on the hydrogel phantom as therapeutic electric field generating pad locations (step 320).

[0104] Figure 7 is a flowchart of an exemplary method 400 for verifying the simulation of TTField intensity (i.e., the estimated TTField intensity predicted in the computer model) according to this disclosure. Furthermore, according to this disclosure, instead of, or in addition to, TTField intensity, the following can also be verified: voltage, amperage, temperature, or several combinations thereof.

[0105] In step 402, one or more computer simulations can determine an estimated TTField intensity for a target area in the body. Generally, the computer simulation determines the position of electrodes for TTField treatment. One or more computer models of electrical conductivity in the body (e.g., head, torso) can be generated by obtaining CT scans and / or MRI images of specific parts of the body. For example, the disclosures in the following patents and patent publications detail the segmentation of CT scans and / or MRI images to provide computer models of conductivity used to determine the position of electrodes in TTField treatment: U.S. Patent No. 10,188,851 filed October 27, 2016; U.S. Patent Publication No. 2020 / 0146586 filed November 12, 2019; and U.S. Patent Publication No. 2020 / 0023179 filed July 18, 2019; all of those documents are incorporated herein by reference in their entirety. In computer simulations, the estimated TTField intensity can be determined in relation to a target area in the body (e.g., a tumor) based on the simulated positioning of the electrodes.

[0106] In step 404, the actual TTField intensity within the hydrogel phantom 78 can be obtained in accordance with this disclosure using the hydrogel phantom 78. The electric field generating pads 70a and 70b can be positioned around the hydrogel phantom 78 based on the positioning of electrodes in a computer simulation or model. An alternating electric field can be applied to the hydrogel phantom 78 by the electric field generating pads 70a and 70b. The actual TTField intensity can be measured in relation to the alternating electric field passing through at least a portion of the hydrogel phantom 78.

[0107] In step 406, the estimated TTField intensity from the computer simulation and the actual TTField intensity of the hydrogel phantom 78 are compared, and a resulting comparison output can be provided. In step 408, the resulting comparison output can be used to validate the computer simulation of the estimated TTField intensity, and / or to update the computer simulation. For example, the resulting comparison output can be used to validate the estimated TTField intensity provided by the computer simulation if the difference between the actual TTField intensity and the estimated TTField intensity is within a predetermined threshold. In some embodiments, the resulting comparison can be used to adjust or calibrate the computer simulation (e.g., to update one or more algorithms in the computer simulation).

[0108] The following is a numbered list of non-limiting exemplary embodiments of the inventive concept disclosed herein.

[0109] 1. A hydrogel phantom comprising a plurality of connected hydrogel elements, wherein the first hydrogel element has a first electrical impedance, the second hydrogel element has a second impedance, and the first impedance is different from the second impedance.

[0110] 2. A hydrogel phantom according to exemplary embodiment 1, wherein multiple connected hydrogel elements are shaped like parts of a patient's body.

[0111] 3. A hydrogel phantom according to exemplary embodiment 1, wherein at least one of the hydrogel elements is in the form of a tumor, and at least one of a plurality of adjacently arranged hydrogel elements has an impedance that mimics the impedance of a tumor.

[0112] 4. A hydrogel phantom according to exemplary embodiment 1, wherein multiple connected hydrogel elements are shaped like a human head.

[0113] 5. A hydrogel phantom according to exemplary embodiment 1, wherein each of the multiple connected hydrogel elements comprises a first component and a second component in a predetermined ratio.

[0114] 6. The hydrogel phantom according to exemplary embodiment 1, further comprising a non-gel element communicating with at least one of a plurality of connected hydrogel elements.

[0115] 7. A hydrogel phantom according to exemplary embodiment 6, wherein the non-gel element is a medical device that communicates with at least one of a plurality of adjacently arranged hydrogel elements.

[0116] 8. A hydrogel phantom according to exemplary embodiment 6, wherein non-gel elements are embedded within a plurality of adjacently arranged hydrogel elements.

[0117] 9. A step of receiving a three-dimensional model of an object, wherein the three-dimensional model has multiple voxels, and each voxel is provided with characteristic information that can be used to identify or determine at least one of impedance or resistance related to the voxel; The steps involve operating a gel coating system to generate a hydrogel phantom using a 3D model, by generating hydrogel elements corresponding to voxels in the 3D model within the hydrogel phantom, and Methods that include...

[0118] 10. A step of attaching an electric field generating pad to a hydrogel phantom at a specific location on the hydrogel phantom, wherein the hydrogel phantom has a plurality of connected hydrogel elements, the first of which has a first electrical impedance, the second of which has a second impedance, and the first impedance is different from the second impedance; The steps include: applying an alternating electric field to the hydrogel phantom using an electric field generating pad; The steps include measuring at least one property related to an alternating electric field passing through at least a portion of the hydrogel phantom using multiple sensors; The following steps: A step of determining the effectiveness of an alternating electric field on a target region within a hydrogel phantom; and, The step of modeling the alternating electric field passing through at least a portion of the hydrogel phantom using data measured by multiple sensors. A step of performing at least one of the following: Methods that include...

[0119] 11. The method according to an exemplary embodiment 10, wherein the step of applying an alternating electric field includes the step of applying a tumor-treating electric field to a hydrogel phantom by an electric field generating pad.

[0120] 12. The method according to an exemplary embodiment 10, further comprising the step of calculating the specific absorption rate of an alternating electric field by a hydrogel phantom, at least in part, based on at least one measured characteristic related to the alternating electric field.

[0121] 13. The method according to an exemplary embodiment 10, further comprising the step of attaching a plurality of sensors associated with a particular portion of a hydrogel phantom to or within a hydrogel phantom, wherein each sensor provides at least one property.

[0122] 14. The method according to an exemplary embodiment 13, wherein the step of measuring at least one characteristic related to an alternating electric field further includes the step of measuring at least one of a plurality of sensors to determine at least one characteristic.

[0123] 15. The method of an exemplary embodiment 14, further comprising the step of measuring at least one characteristic related to an alternating electric field to determine the temperature related to an alternating electric field passing through a particular portion of the hydrogel phantom, wherein the step of measuring at least one of a plurality of sensors is further included.

[0124] 16. The method of an exemplary embodiment 14, further comprising the step of measuring at least one property related to an alternating electric field to determine an electrical property related to an alternating electric field passing through a particular portion of the hydrogel phantom.

[0125] 17. The method of an exemplary embodiment 14, further comprising the step of measuring at least one property related to an alternating electric field to determine a magnetic property related to an alternating electric field passing through a particular portion of the hydrogel phantom, wherein the step of measuring at least one of one or more sensors is further included.

[0126] 18. The method according to exemplary embodiment 14, wherein the step of applying an alternating electric field includes the step of applying a tumor-treating electric field to the hydrogel phantom by an electric field generating pad.

[0127] 19. The method according to an exemplary embodiment 18, wherein the step of modeling a tumor therapeutic electric field includes determining the effectiveness of an alternating electric field on a target region in a hydrogel phantom.

[0128] 20. A step of attaching an electric field generating pad to a hydrogel phantom at a location predetermined based on computer simulation, wherein the hydrogel phantom has a plurality of hydrogel elements, the first of which has a first electrical impedance, the second of which has a second impedance, and the first impedance is different from the second impedance; The steps include: applying an alternating electric field to the hydrogel phantom using an electric field generating pad; To obtain the actual TTField intensity, the steps include: measuring the TTField intensity related to the alternating electric field passing through at least a portion of the hydrogel phantom; The steps include comparing the actual TTField intensity with the estimated TTField intensity obtained from computer simulations, and Methods that include...

[0129] 21. The method according to exemplary embodiment 20, wherein the electric field generating pad is attached to the outer wall of the hydrogel phantom.

[0130] 22. The method according to the exemplary embodiment 20, wherein the second impedance of the second hydrogel element matches the impedance of the tumor.

[0131] 23. The method according to an exemplary embodiment 22, wherein a second hydrogel element is attached to a probe configured to measure TTField intensity, and the method further includes the step of moving the probe relative to the first hydrogel element.

[0132] From the above description, it is clear that the inventive concepts disclosed and claimed herein are well adapted to perform the purposes and obtain the advantages described herein, as well as those specific to the present invention. For the purposes of this disclosure, exemplary embodiments of the inventive concepts have been described, but numerous variations are possible, and it will be understood that numerous variations will be readily apparent to those skilled in the art and will be achieved in the spirit of the inventive concepts disclosed and claimed herein. Features disclosed in the foregoing description, exemplary embodiments, or the following claims, or in the accompanying drawings (which are expressed in their particular forms, or in terms of means for performing the disclosed functions, or in terms of methods or processes for obtaining the disclosed results), can be used individually or in any combination of such features to realize this disclosure in a variety of forms. [Explanation of symbols]

[0133] 10 dividing cells 14 Lines of Force 18a First electrode 18b Second electrode 22 Microtubules 26 centriole 30 Center of a dividing cell 34 Key points for attaching microtubules 22 to the cell membrane 50 Electronic equipment 54 Generator 58 Conductive Leads 58a First conductive lead 58b Second conductive lead 62a First end 62b Second end 66a First end 66b Second end 70a First electric field generating pad 70b Second electric field generating pad 74 Electric Field Target 78 Hydrogel Phantom 82a~n Hydrogel Elements 82a Hydrogel element 82b Hydrogel element 82c Skin Hydrogel Element 82c' Partial skin hydrogel element 82d Bone Hydrogel Element 82d' Partial bone hydrogel element 82e Brain Hydrogel Element 82f Target Hydrogel Element 82g First hydrogel element 84 Outer surface 86 Control Box 90 Temperature Sensor 100 Hydrogel Phantom Heads 100' Partial Phantom Head 102a~n Sensor 102a First sensor 102b Second sensor 104a~n Sensor Lead 108a~n Simulated veins 112 Non-gel element 120 External devices 130 Fluid Containers 134 Exterior wall section 136 External surface 140 Fluid Solutions 142 Movable probe 200 Gel Dispensing System 200a Gel Dispensing System 204 Applicators 204a First Applicator 204b Second Applicator 208 Platforms 212 Housing 216 Nozzles 216a First nozzle 216b Second nozzle 220 First direction 224 Second direction 228 Third Direction 228 Controllers 229 memory 230 Processors 232 Curing equipment 234 voxels

Claims

1. A step of attaching an electric field generating pad to a hydrogel phantom at a specific location on the hydrogel phantom, wherein the hydrogel phantom has a plurality of connected hydrogel elements, the first of the hydrogel elements having a first electrical impedance, the second of the hydrogel elements having a second impedance, the first impedance being different from the second impedance; The steps include: applying an alternating electric field to the hydrogel phantom using the electric field generating pad; The steps include: measuring, using multiple sensors, at least one characteristic related to the alternating electric field passing through at least a portion of the hydrogel phantom; The following steps: A step of determining the effectiveness of the alternating electric field on a target region within the hydrogel phantom; and, The step of modeling the alternating electric field passing through at least a portion of the hydrogel phantom using data measured by the plurality of sensors. A step of performing at least one of the following: Methods that include...

2. The method according to claim 1, wherein the step of applying an alternating electric field includes the step of applying a tumor treatment electric field to the hydrogel phantom with the electric field generating pad.

3. The method according to claim 1, further comprising the step of calculating the specific absorption rate of the alternating electric field by the hydrogel phantom, at least partially based on the measured at least one characteristic relating to the alternating electric field.

4. The method according to claim 1, further comprising the step of attaching the plurality of sensors associated with a particular portion of the hydrogel phantom to or within the hydrogel phantom, wherein each sensor provides at least one property.

5. The method according to claim 4, wherein the step of measuring at least one characteristic related to the alternating electric field further includes the step of measuring at least one of the plurality of sensors in order to determine the at least one characteristic.

6. The method according to claim 5, wherein the step of measuring at least one characteristic related to the alternating electric field further includes the step of measuring at least one of the plurality of sensors to determine the temperature related to the alternating electric field passing through the particular portion of the hydrogel phantom.

7. The method according to claim 5, wherein the step of measuring at least one characteristic related to the alternating electric field further includes the step of measuring at least one of the one or more sensors to determine the electrical characteristics related to the alternating electric field passing through the particular portion of the hydrogel phantom.

8. The method according to claim 5, wherein the step of measuring at least one property related to the alternating electric field further includes the step of measuring at least one of the one or more sensors to determine the magnetic property related to the alternating electric field passing through the particular portion of the hydrogel phantom.

9. The method according to claim 5, wherein the step of applying an alternating electric field includes the step of applying a tumor treatment electric field to the hydrogel phantom with the electric field generating pad.

10. The method according to claim 9, wherein the step of modeling the tumor treatment electric field includes the step of determining the effectiveness of the alternating electric field on a target region in the hydrogel phantom.

11. A step of attaching an electric field generating pad to a hydrogel phantom at a location predetermined based on computer simulation, wherein the hydrogel phantom has a plurality of hydrogel elements, the first of the hydrogel elements having a first electrical impedance, the second of the hydrogel elements having a second impedance, the first impedance being different from the second impedance; The steps include: applying an alternating electric field to the hydrogel phantom using the electric field generating pad; To obtain the actual TTField intensity, the steps include: measuring the TTField intensity related to the alternating electric field passing through at least a portion of the hydrogel phantom; The steps include comparing the actual TTField intensity with the estimated TTField intensity obtained from the computer simulation. Methods that include...

12. The method according to claim 11, wherein the electric field generating pad is attached to the outer wall portion of the hydrogel phantom.

13. The method according to claim 11, wherein the second impedance of the second hydrogel element matches the impedance of the tumor.

14. The method according to claim 13, wherein the second hydrogel element is attached to a probe configured to measure TTField intensity, and the method further comprises the step of moving the probe relative to the first hydrogel element.

15. The method according to claim 11, wherein the hydrogel phantom represents a human head.

16. The method according to claim 11, wherein the first of the hydrogel elements is a skin hydrogel element, a bone hydrogel element, or a brain hydrogel element, and the impedance of the first is matched to the impedance of the corresponding biological component.

17. The method according to claim 11, wherein each of the plurality of hydrogel elements is formed from two or more constituent hydrogels, and each of the two or more constituent hydrogels is a conductive gel having one or more structurally water-soluble polymers, one or more crosslinking agents, one or more photoinitiators, one or more electrolytes, and one or more additives.

18. The method according to claim 11, wherein the comparison result of the comparison step is used for calibrating the computer simulation.

19. The method according to claim 11, wherein the estimated TTField intensity is determined with respect to the target area.

20. The method according to claim 19, wherein the target area is a tumor.

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