Tumor therapy electric field (TTField) application with temperature sensor positioned between electrode element and subject skin

Abstract

An alternating electric field (e.g., a tumor therapy electric field or TTField) may be applied to a subject's body by positioning electrode elements on opposing sides of a target region in the subject's body and applying an AC voltage between the opposing electrode elements. A temperature sensor positioned in front of the electrode element (i.e., between the electrode element and the skin of the subject) and in thermal contact with the skin of the subject is used to monitor the temperature of the skin of the subject. The current applied to the electrode element is adjusted to a highest possible level that does not cause the subject's skin to exceed a safety threshold (e.g., 41 DEG C). Optionally, one or more heat exchangers are included to remove heat from the electrode element, in which case a greater current will be likely to be driven through the electrode element without exceeding the safety threshold.

Description

[0001] Cross-reference to related applications This application claims the benefit of U.S. Provisional Application No. 63 / 541,351, filed on September 29, 2023, the entire contents of which are incorporated herein by reference. Background Technology

[0002] Tumor therapeutic electric field (TTField) therapy is a proven cancer treatment method that uses an alternating electric field with a frequency, for example, between 50 kHz and 5 MHz (more commonly 100 kHz to 500 kHz). The alternating electric field is induced by electrode assemblies (e.g., an array of capacitively coupled electrodes, also known as a transducer array) placed on the skin of the subject on opposite sides of the subject's body. When an AC voltage is applied between the opposing electrode assemblies, an AC current is coupled through the electrode assemblies and enters the subject's body.

[0003] Higher current is closely associated with higher therapeutic efficacy. However, the current cannot be arbitrarily set to a high value because both the electrode assembly and the skin beneath it will generate heat during use, and safety considerations require that the skin temperature not exceed a threshold (e.g., 41°C).

[0004] U.S. Patent 8,715,203 describes an example of an electrode assembly that can be used to apply an alternating electric field to a subject's body. In this example, a thermistor is positioned in a small hole at the center of an electrode element within the electrode assembly and is in thermal contact with the electrode element. U.S. Patent Publication No. 2021 / 0402179 describes another example of an electrode assembly that can be used to apply an alternating electric field to a subject's body. In this example, a thermistor is positioned behind the electrode element and is in thermal contact with the electrode element. Prior art systems rely on signals from these thermistors to ensure that the current is low enough to prevent the subject's skin temperature from exceeding a safe threshold. Summary of the Invention

[0005] One aspect of the invention relates to a first device for applying an alternating electric field to a subject's body. The first device includes at least one electrode element, a support, and a plurality of temperature sensors. Each electrode element has a corresponding front face with a corresponding area. The support is configured to hold the at least one electrode element near the subject's body such that the front face of the at least one electrode element faces the subject's body. The plurality of temperature sensors are positioned in front of the at least one electrode element such that when the support holds the at least one electrode element near the subject's body, the plurality of temperature sensors are positioned between the front face of the at least one electrode element and the subject's body and are in thermal contact with the subject's body.

[0006] In some embodiments of the first device, each temperature sensor in the temperature sensor includes a thermistor.

[0007] Some embodiments of the first device also include a plurality of insulated wires positioned in front of the at least one electrode element, wherein the plurality of insulated wires are configured to route electrical signals to the temperature sensor. Optionally, in these embodiments, the plurality of temperature sensors and the plurality of insulated wires together occupy an area less than 10% of the sum of the areas of all the electrode elements.

[0008] Some embodiments of the first device also include a flexible circuit configured to support the plurality of temperature sensors and provide an electrical interface with the plurality of temperature sensors. Optionally, in these embodiments, the flexible circuit has an insulating substrate and a plurality of conductive traces, the flexible circuit being oriented such that the insulating substrate is positioned in front of the plurality of conductive traces, and the insulating substrate being shaped and sized to prevent the plurality of conductive traces from contacting the subject's body.

[0009] In some embodiments of the first device, the support is positioned behind the at least one electrode element.

[0010] Some embodiments of the first device also include a heat exchanger configured to be in thermal contact with the at least one electrode element, wherein the heat exchanger is positioned behind the at least one electrode element and configured to remove heat from the at least one electrode element.

[0011] Optionally, in the embodiments described in the previous paragraph, the heat exchanger may rely on the flow of a liquid to remove the heat. Optionally, in the embodiments described in the previous paragraph, the heat exchanger may include a passive radiator positioned in contact with a low-temperature object.

[0012] Some embodiments of the first device further include an insulating material layer having a dielectric constant greater than 10 and disposed on the front side of the at least one electrode element. In these embodiments, the plurality of temperature sensors are positioned in front of the insulating material layer.

[0013] Some embodiments of the first device further include: an insulating material layer having a dielectric constant greater than 10 and disposed on the front side of the at least one electrode element, wherein the insulating material layer has a front side; and a graphite sheet disposed on the front side of the insulating material layer. In these embodiments, the plurality of temperature sensors are positioned in front of the graphite layer.

[0014] Optionally, the embodiments described in the preceding paragraph may also include a heat exchanger configured to be in thermal contact with the at least one electrode element, wherein the heat exchanger is positioned behind the at least one electrode element and configured to remove heat from the at least one electrode element.

[0015] Some embodiments of the first device also include a graphite sheet and a conductive adhesive layer. The graphite sheet is disposed in front of the plurality of temperature sensors such that when the support holds the at least one electrode element near the subject's body, the graphite sheet is positioned between the plurality of temperature sensors and the subject's body. The conductive adhesive layer is disposed in front of the graphite sheet such that when the support holds the at least one electrode element near the subject's body, the conductive adhesive layer is positioned between the graphite sheet and the subject's body.

[0016] Another aspect of the invention relates to a second device for applying an alternating electric field to a subject's body. The second device includes a plurality of electrode elements, a support, a flexible circuit, and a plurality of temperature sensors. Each of the electrode elements has a corresponding front face with a corresponding area. The support is configured to hold the plurality of electrode elements near the subject's body such that the front faces of the electrode elements face the subject's body. The flexible circuit has an insulating substrate and a plurality of conductive traces, and is positioned such that when the support holds the plurality of electrode elements near the subject's body, the flexible circuit is positioned between the front faces of the electrode elements and the subject's body. The plurality of temperature sensors are attached to the flexible circuit, and the conductive traces of the flexible circuit are configured to provide electrical interfaces with the temperature sensors.

[0017] In some embodiments of the second device, each temperature sensor in the temperature sensor includes a thermistor.

[0018] In some embodiments of the second device, the flexible circuit is shaped and sized to cover less than 10% of the sum of the areas of all the electrode elements. Alternatively, in these embodiments, the sum of the areas of all the electrode elements is at least 10 cm².

[0019] In some embodiments of the second device, the flexible circuit is oriented such that the insulating substrate is in front of the plurality of conductive traces, and the insulating substrate is shaped and sized to prevent the plurality of conductive traces from coming into contact with the subject's body.

[0020] Some embodiments of the second device also include a heat exchanger configured to be in thermal contact with the plurality of electrode elements, wherein the heat exchanger is positioned behind the plurality of electrode elements and configured to remove heat from the plurality of electrode elements.

[0021] Another aspect of the invention relates to a third device for applying an alternating electric field to a subject's body. The third device includes at least one electrode element, a support, a plurality of temperature sensors, and a flexible circuit. Each electrode element has a corresponding front face with a corresponding area. The support is configured to hold the at least one electrode element near the subject's body such that the front face of the at least one electrode element faces the subject's body. The plurality of temperature sensors are positioned in front of the at least one electrode element such that when the support holds the at least one electrode element near the subject's body, the plurality of temperature sensors are positioned between the front face of the at least one electrode element and the subject's body and are in thermal contact with the subject's body. The flexible circuit has an insulating substrate and a plurality of conductive traces. The at least one electrode element includes a plurality of electrode elements. The flexible circuit is positioned such that when the support holds the plurality of electrode elements near the subject's body, the flexible circuit is positioned between the front face of the plurality of electrode elements and the subject's body. The plurality of temperature sensors are attached to the flexible circuit, and the plurality of conductive traces of the flexible circuit are configured to provide an electrical interface with the plurality of temperature sensors.

[0022] In some embodiments of the third device, each temperature sensor in the temperature sensor includes a thermistor.

[0023] In some embodiments of the third device, the flexible circuit is shaped and sized to cover less than 10% of the sum of the areas of all the electrode elements. Alternatively, in these embodiments, the sum of the areas of all the electrode elements is at least 10 cm².

[0024] Another aspect of the invention relates to a first method for applying an alternating electric field to a subject's body. The first method includes: positioning at least one first electrode element against the subject's body, wherein a plurality of first temperature sensors are sandwiched between the at least one first electrode element and the subject's body such that the first temperature sensors are in thermal contact with the subject's body, wherein each of the at least one first electrode element has a corresponding rear surface. The first method further includes: positioning a first heat exchanger in thermal contact with the rear surface of the at least one first electrode element. The first method further includes: positioning at least one second electrode element against the subject's body, wherein a plurality of second temperature sensors are sandwiched between the at least one second electrode element and the subject's body such that the second temperature sensors are in thermal contact with the subject's body, wherein each of the at least one second electrode element has a corresponding rear surface. The first method further includes: positioning a second heat exchanger in thermal contact with the rear surface of the at least one second electrode element. The first method further includes: applying an alternating voltage between the at least one first electrode element and the at least one second electrode element; passing a first cooling fluid through the first heat exchanger to remove heat from the at least one first electrode element; passing a second cooling fluid through the second heat exchanger to remove heat from the at least one second electrode element; determining a plurality of first temperatures based on the outputs of the plurality of first temperature sensors; and determining a plurality of second temperatures based on the outputs of the plurality of second temperature sensors. The first method further includes: adjusting at least one of the following based on the determined plurality of first temperatures: (a) the amplitude of the alternating voltage, and (b) the passage of the first cooling fluid through the first heat exchanger; and adjusting at least one of the following based on the determined plurality of second temperatures: (i) the amplitude of the alternating voltage, and (ii) the passage of the second cooling fluid through the second heat exchanger.

[0025] In some instances of the first method, the at least one first electrode element comprises a plurality of first electrode elements, and each of the plurality of first temperature sensors is sandwiched between a corresponding first electrode element and the subject's body. In these instances, the at least one second electrode element comprises a plurality of second electrode elements, and each of the plurality of second temperature sensors is sandwiched between a corresponding second electrode element and the subject's body.

[0026] In some instances of the first method, each of the first temperature sensors in the first temperature sensor and each of the second temperature sensors in the second temperature sensor includes a thermistor.

[0027] Another aspect of the invention relates to a kit for applying an alternating electric field to a subject's body. The kit includes: (1) a first component comprising: (a) a plurality of electrode elements, each of which has a corresponding front face with a corresponding area; and (b) a support configured to hold the plurality of electrode elements near the subject's body such that the front faces of the plurality of electrode elements face the subject's body; and (2) a second component comprising: (i) a flexible circuit including an insulating substrate and a plurality of conductive traces; and (ii) a plurality of temperature sensors attached to the flexible circuit. The plurality of conductive traces of the flexible circuit are configured to provide an electrical interface with the plurality of temperature sensors. The flexible circuit is configured to adapt between the front faces of the plurality of electrode elements and the subject's body when the support holds the plurality of electrode elements near the subject's body. Attached Figure Description

[0028] Figure 1 An example of a system that uses two electrode components to apply a TTField to a subject's body is described.

[0029] Figure 2 Depicting what is included Figure 1 One component within each of the electrode assemblies depicted.

[0030] Figure 3 Depicting what is included Figure 1 The second component within each of the electrode assemblies depicted.

[0031] Figure 4 Depicting being attached to Figure 3 The components depicted Figure 2 The components depicted.

[0032] Various embodiments are described in detail below with reference to the accompanying drawings, wherein the same reference numerals denote the same elements. Detailed Implementation

[0033] It is worth noting that in existing technology systems, the thermistor is positioned in thermal contact with the electrode element within the electrode assembly (rather than in direct thermal contact with the subject's skin). Therefore, a thermal gradient exists between the thermistor and the subject's skin. However, because this thermal gradient is relatively small, the temperature measurement obtained at the electrode element can still be used as a reliable substitute for the subject's skin temperature, provided the system takes this gradient into account. Existing technology systems account for this thermal gradient by controlling the current, ensuring that the thermistor temperature does not exceed a threshold below a safety threshold. For example, since the safety threshold is 41°C, some existing technology systems control the current to the electrode assembly to keep the thermistor temperature below 39.7°C. And because the thermal gradient between the thermistor and the subject's skin is relatively small, keeping the electrode element temperature below 39.7°C (using thermistor-based measurements) is sufficient to ensure that the skin temperature remains below 41°C.

[0034] One method for increasing the current (and thus improving therapeutic efficacy) without exceeding a safe threshold of 41°C is to cool the electrode assembly (e.g., using a heat exchanger). Examples of suitable heat exchangers for this purpose include those relying on ice packs or circulating cooling water. However, in systems using higher currents coupled to a heat exchanger, the temperature gradient between the subject's skin and the thermistor positioned in thermal contact with the electrode element can increase to such an extent that measuring the temperature of the electrode element no longer provides a reliable alternative to directly measuring the temperature of the subject's skin. This is especially true when the thermistor is positioned behind the electrode assembly and the heat exchanger is also positioned behind the electrode assembly. Due to this arrangement of components, the thermistor will be cooled to a maximum extent, the electrode element to a lower extent, and the subject's skin to an even lower extent. This can result in a significant temperature difference between the thermistor and the subject's skin.

[0035] The embodiments described below involve positioning a temperature sensor (e.g., a thermistor) on the electrode element. Front This problem is addressed by placing the temperature sensor closer to the subject's skin (i.e., between the electrode elements in the electrode assembly and the subject's skin) and making thermal contact with the subject's body. By positioning the temperature sensor closer to the subject's skin (compared to existing technologies), the temperature gradient between the temperature sensor and the subject's skin is significantly reduced, making the temperature readings obtained from the temperature sensor more reliable.

[0036] Figure 1An example of a system for applying a TTField to a subject's body using two electrode assemblies 50 (E1 to E9) and 60 (T1 to T9) is depicted. Each of these electrode assemblies has a set of temperature sensors 60 positioned in front of the electrode elements E1 to E9 within each of these electrode assemblies. Optionally, a separate heat exchanger 70 is used to cool each of these electrode assemblies. In an alternative embodiment (not shown), a single heat exchanger may be used to cool both electrode assemblies.

[0037] Figure 1 Each electrode assembly in the embodiments includes at least one electrode element E1 to E9, and each of these electrode elements has a corresponding front side with a corresponding area. The following is in conjunction with... Figure 2 The described support (e.g., PCB 50 and flexible backing 80) is configured to hold at least one electrode element E1 to E9 near the subject's body such that the front of the at least one electrode element faces the subject's body. A plurality of temperature sensors T1 to T9 (e.g., thermistors) are positioned in front of the at least one electrode element E1 to E9 such that when the support holds the at least one electrode element near the subject's body, the plurality of temperature sensors T1 to T9 are positioned between the front of the at least one electrode element E1 to E9 and the subject's body and are in thermal contact with the subject's body.

[0038] Figures 2 to 4 An example of a suitable two-part method is described, which is used to implement a support for holding electrode elements E1 to E9 in each electrode assembly in the electrode assembly near the subject's body, and for positioning temperature sensors T1 to T9 between the front of the electrode elements E1 to E9 and the subject's body.

[0039] Figure 2 The first part of the two-part method is described, which has a first flexible circuit 50 (i.e., a flexible PCB) with a plurality of conductive metal pads (e.g., copper pads) disposed on its front side. These metal pads serve as electrode elements E1 to E9. For example, the first flexible circuit 50 can be implemented using copper traces and pads formed on a polyimide substrate. However, alternative metals and / or alternative insulating substrates can be used instead of copper and polyimide. A flexible backing 80 is disposed behind the substrate of the first flexible circuit 50.

[0040] Optionally, one or more additional material layers may be positioned in front of the electrode elements E1 to E9 within the first part of the two-part method. For example, in some embodiments, an insulating material layer having a high dielectric constant (e.g., >10, >20, or >40) is positioned on the front side of each of the electrode elements E1 to E9. This insulating material layer may be implemented as a single large sheet covering all the electrode elements E1 to E9, or it may be implemented as a set of nine smaller pads, each sized and positioned to cover a corresponding electrode element among the electrode elements E1 to E9. The purpose of this insulating material layer is to capacitively couple the electrode elements E1 to E9 to the subject's body via any conductive layer positioned between the insulating material layer and the subject's body. On the other hand, when no insulating material layer is provided, the electrode elements E1 to E9 will be conductively coupled to the subject's body via any conductive layer positioned between the electrode elements E1 to E9 and the subject's body.

[0041] In another example, a sheet of graphite or another anisotropic material may be positioned in front of all electrode elements E1 to E9 within the first part of the two-part method. The purpose of this layer is to diffuse heat and current in a direction parallel to the plane of the electrode assembly. In yet another example, as described above, an insulating material layer is positioned on the front side of each of the electrode elements E1 to E9, and a graphite sheet is positioned in front of this insulating material layer (optionally, a conductive adhesive sheet is positioned between them). This example provides both capacitive coupling and the diffusion of heat and current within the first part of the two-part method.

[0042] Figure 3 The second part of the two-part method is described, which has a second flexible circuit 60 and a plurality of temperature sensors T1 to T9 (e.g., thermistors) attached thereto. The second flexible circuit 60 is configured to support the plurality of temperature sensors T1 to T9 and provide an electrical interface with the plurality of temperature sensors.

[0043] These two parts can be assembled by pressing the second flexible circuit 60 (of the second part) against the front of the electrode elements E1 to E9 (of the first part), thereby forming Figure 4 The depicted configuration includes a flexible backing 80 at the rear, followed by a first flexible circuit 50, and then a second flexible circuit 60 at the front. Electrode elements E1 to E9 are disposed on the front side of the first flexible circuit 50.

[0044] In this example, a second flexible circuit 60 is disposed between the front of a plurality of electrode elements E1 to E9 and the subject's body. The second flexible circuit has an insulating substrate and a plurality of conductive traces, and the second flexible circuit 60 is oriented such that the insulating substrate is in front of the plurality of conductive traces. The insulating substrate is shaped and sized to prevent the plurality of conductive traces on the second flexible circuit 60 from contacting the subject's body. This can be achieved, for example, by ensuring that the conductive traces do not extend all the way to the edge of the insulating substrate. In these embodiments, it is preferred that the flexible circuit is shaped and sized to cover less than 10% of the sum of the areas of all electrode elements, such that the coupling between electrode elements E1 to E9 and the subject's body is not excessively obstructed. In some preferred embodiments, the sum of the areas of all electrode elements E1 to E9 is at least 10 cm². (These embodiments are preferred because a larger area is beneficial for transmitting alternating electric fields and for heat dissipation.) Optionally, an additional layer positioned behind the thermistors T1 to T9 may be included in the electrode assembly. For example, a graphite sheet (not shown) covering the entire front side of the first flexible circuit 50 may be positioned immediately in front of the electrode elements E1 to E9 to diffuse heat and current in a direction parallel to the front side of the electrode assembly. Graphite has the added advantage of preventing ions from flowing into or out of the subject's body. Other materials that block ions and have high thermal conductivity, such as dry conductive carbon binders, may also be used instead of graphite.

[0045] The thermal contact between temperature sensors T1 to T9 and the subject's body can be direct thermal contact or indirect thermal contact through an intermediate component. In some preferred embodiments, steps are taken to improve the thermal contact between temperature sensors T1 to T9 and the subject's body as much as possible. For example, a thin layer of conductive adhesive and / or conductive hydrogel (not shown) may be positioned between temperature sensors T1 to T9 and the subject's body. Alternatively and / or additionally, temperature sensors T1 to T9 may be positioned as close as possible to the subject's skin.

[0046] Typically, reducing the distance between thermistors T1-T9 and the subject's body improves thermal contact between thermistors T1-T9 and the subject's body. In some preferred embodiments, thermal contact between thermistors T1-T9 within the subject's body is maximized by mounting thermistors T1-T9 on the front surface of the second flexible circuit 60 and / or by positioning a thin layer of conductive adhesive and / or conductive hydrogel between the subject's skin and the front surface of the second flexible circuit 60.

[0047] In some preferred embodiments, one or more additional material layers may be positioned between the thermistors T1 to T9, provided they do not excessively affect the thermal contact between the thermistors T1 to T9 and the subject's skin. For this purpose, any such additional layer should preferably be thin and have high thermal conductivity. Examples of materials suitable for such additional layers include graphite sheets coated (on the skin side) with a conductive adhesive (e.g., dry conductive carbon adhesive). And as noted above, both graphite and dry conductive carbon adhesive have the additional advantage of preventing ions from flowing into or out of the subject's body.

[0048] In some alternative embodiments (not shown), the electrode assembly may be provided to the end user as two separate components as a kit, rather than the entire electrode assembly being provided to the end user as a single integrated unit. One of these components in the kit includes electrode elements E1 to E9 and supports 50, 80 configured to hold these electrode elements, while the other component includes a second flexible circuit 60 and temperature sensors T1 to T9. To use these embodiments, the end user can attach the two components to each other and then apply them to their body. Alternatively, the end user can first apply the temperature sensing component to their body and then apply the component with the electrode elements directly to the top (i.e., the rear) of the temperature sensing component. The operation of this embodiment will then be combined with the above. Figures 1 to 4 The described embodiments are the same.

[0049] It should be noted that the above text is combined with... Figures 2 to 4 The described two-part method is not mandatory, and all electrode elements E1 to E9 and temperature sensors T1 to T9 can be incorporated into a single integrated sub-assembly, provided that the temperature sensors T1 to T9 are located between the electrode elements E1 to E9 and the subject's body. For example, in one such embodiment (not shown), instead of mounting the temperature sensors T1 to T9 to a second flexible circuit 60, which is omitted, the temperature sensors T1 to T9 are mounted to an insulated wire mesh positioned in front of at least one electrode element E1 to E9. These insulated wires are configured to route electrical signals to the temperature sensors T1 to T9. In these embodiments, it is preferred that the multiple temperature sensors T1 to T9 and the multiple insulated wires together occupy an area less than 10% of the sum of the areas of all the electrode elements, so that the coupling between the electrode elements E1 to E9 and the subject's body is not excessively obstructed.

[0050] Back Figure 1Each electrode assembly in electrode assemblies 50 (E1 to E9) and 60 (T1 to T9) (i.e., the left-hand electrode assembly and the right-hand electrode assembly) has an associated heat exchanger 70 configured to have thermal contact with at least one electrode element E1 to E9. It should be noted that the thermal contact between the heat exchanger 70 and the at least one electrode element E1 to E9 does not necessarily have to be a direct thermal coupling between these components. Instead, intermediate components may be provided between them, as long as these intermediate components conduct heat between the heat exchanger 70 and the at least one electrode element E1 to E9. The heat exchanger 70 is positioned behind the at least one electrode element E1 to E9 and is configured to remove heat from the at least one electrode element. In some embodiments (including...) Figure 1 In the described embodiment, heat exchanger 70 relies on the flow of a liquid to remove heat. This liquid can be, for example, water, oil, etc. In an alternative embodiment (not shown), the heat exchanger can be a passive radiator positioned in contact with a low-temperature object (e.g., a cooling blanket, ice, etc.). In another alternative embodiment (not shown), instead of positioning separate heat exchangers 70 at each of these electrode assemblies, a single heat exchanger can be used to cool both electrode assemblies. In other alternative embodiments, the heat exchanger is omitted.

[0051] In order to use Figure 1 The described system applies a TTField to a target region in a subject's body. First electrode assemblies 50 (E1 to E9) and 60 (T1 to T9) are positioned such that at least one first electrode element E1 to E9 within the first electrode assembly is positioned against the subject's body. A plurality of first temperature sensors T1 to T9 are sandwiched between the at least one first electrode element and the subject's body, such that the first temperature sensors are in thermal contact with the subject's body. Second electrode assemblies 50 (E1 to E9) and 60 (T1 to T9) are positioned such that at least one second electrode element E1 to E9 within the second electrode assembly is positioned against the subject's body. A plurality of second temperature sensors T1 to T9 are sandwiched between the at least one second electrode element and the subject's body, such that the second temperature sensors are in thermal contact with the subject's body. Each of the at least one first electrode element and each of the at least one second electrode element has a corresponding rear surface.

[0052] A first heat exchanger 70 is positioned to make thermal contact with the rear surface of at least one first electrode element E1 to E9, and a second heat exchanger 70 is positioned to make thermal contact with the rear surface of at least one second electrode element E1 to E9. (It should be noted again that these thermal contacts can be direct thermal contacts or indirect thermal contacts through intermediate components.) Applying an alternating voltage between the at least one first electrode element E1 to E9 and the at least one second electrode element E1 to E9 couples an electric field into the subject's body, and this electric field is transmitted through the target area. This causes the at least one first electrode element E1 to E9 and the at least one second electrode element E1 to E9 to heat above ambient temperature, and the amount of heating will depend on the current transmitted through the at least one first electrode element and the at least one second electrode element.

[0053] A first heat exchanger 70 removes heat from at least one first electrode element E1 to E9, and a second heat exchanger 70 removes heat from at least one second electrode element E1 to E9. Figure 1 In the example, each of these heat exchangers operates by passing a corresponding cooling fluid through the heat exchanger. However, in alternative embodiments, other types of heat exchangers (e.g., passive heat exchangers) may be used.

[0054] Since the temperature sensors T1 to T9 are in thermal contact with the subject's body, the temperature of the subject's skin in front of the first electrode assembly and the second electrode assembly can be monitored by the first temperature sensors T1 to T9 and the second temperature sensors T1 to T9 embedded in the first electrode assembly and the second electrode assembly, respectively. This is achieved by determining multiple first temperatures based on the outputs of the multiple first temperature sensors T1 to T9, and determining multiple second temperatures based on the outputs of the multiple second temperature sensors T1 to T9.

[0055] The amplitude of the AC voltage and / or the transfer of the first cooling fluid through the first heat exchanger 70 are adjusted based on a plurality of determined first temperatures. The amplitude of the AC voltage and / or the transfer of the second cooling fluid through the second heat exchanger 70 are also adjusted based on a plurality of determined second temperatures. These adjustments are preferably designed such that the current from the AC voltage generator 20 is as high as possible without raising the temperature of the subject's skin beneath the electrode assembly above a safe threshold (e.g., 41°C).

[0056] It is worth noting that, because temperature sensors T1 to T9 are positioned in front of their respective electrode elements E1 to E9 within the corresponding electrode assembly, making thermal contact with the subject's body, each temperature sensor T1 to T9 will more accurately reflect the subject's skin temperature (compared to existing techniques where temperature sensors are not positioned in front of the electrode elements). This is because... Figures 1 to 4In this embodiment, the thermistors T1 to T9 are in thermal contact with the subject's body and are closer to the subject's skin than thermistors in the prior art. This allows the system to operate at a higher current than prior art systems without the risk of the temperature of the subject's skin beneath the electrode assembly exceeding a safe threshold. For example, prior art Optune® systems used to apply TTFields to the subject's body always operate below 4A for thermal reasons. However, when active cooling is combined with a temperature sensor positioned in thermal contact with the subject's body and located in front of the electrode elements, as described herein, the system can achieve significantly higher currents (e.g., >5A, >6A, >8A, >10A, >12A, or >15A). These higher operating currents will result in greater therapeutic efficacy.

[0057] Finally, although the above text uses nine electrode elements E1 to E9 and nine temperature sensors T1 to T9 as examples and descriptions Figures 1 to 4 The illustrated embodiments are shown, but the number of electrode elements and the number of temperature sensors may vary (e.g., from 1 to 50). Similarly, although Figure 1 Two electrode assemblies are depicted (i.e., one electrode assembly located on the left side of the target region and one electrode assembly located on the right side of the target region), but more than two electrode assemblies (e.g., three, four or more) can be used.

[0058] While the invention has been disclosed with reference to certain embodiments, various modifications, alterations, and changes can be made to the described embodiments without departing from the scope and domain of the invention as defined by the appended claims. Therefore, the invention is intended to be limited to the described embodiments, but rather to have the full scope defined by the language of the appended claims and their equivalents.

Claims

1. A device for applying an alternating electric field to the body of a subject, the device comprising: At least one electrode element, wherein each electrode element has a corresponding front side with a corresponding area; A support member configured to hold the at least one electrode element near the subject's body such that the front of the at least one electrode element faces the subject's body; and Multiple temperature sensors are positioned in front of the at least one electrode element such that when the support holds the at least one electrode element near the subject's body, the multiple temperature sensors are positioned between the front of the at least one electrode element and the subject's body and are in thermal contact with the subject's body.

2. The apparatus of claim 1, wherein each of the temperature sensors comprises a thermistor.

3. The apparatus of claim 1, further comprising a plurality of insulated wires positioned in front of the at least one electrode element, wherein the plurality of insulated wires are configured to route an electrical signal to the temperature sensor.

4. The apparatus of claim 3, wherein the plurality of temperature sensors and the plurality of insulated wires together occupy an area less than 10% of the sum of the areas of all the electrode elements.

5. The apparatus of claim 1, further comprising a flexible circuit configured to support the plurality of temperature sensors and provide an electrical interface with the plurality of temperature sensors.

6. The apparatus of claim 5, wherein the flexible circuit has an insulating substrate and a plurality of conductive traces, wherein the flexible circuit is oriented such that the insulating substrate is positioned in front of the plurality of conductive traces; and The insulating substrate is shaped and sized to prevent the multiple conductive traces from coming into contact with the subject's body.

7. The apparatus of claim 1, wherein the support is positioned behind the at least one electrode element.

8. The apparatus of claim 1, further comprising a heat exchanger configured to be in thermal contact with the at least one electrode element, wherein the heat exchanger is positioned behind the at least one electrode element and configured to remove heat from the at least one electrode element.

9. The apparatus of claim 8, wherein the heat exchanger relies on the flow of a liquid to remove the heat.

10. The apparatus of claim 1, further comprising an insulating material layer having a dielectric constant greater than 10 and disposed on the front side of the at least one electrode element. The plurality of temperature sensors are positioned in front of the insulating material layer.

11. The apparatus according to claim 1, further comprising: An insulating material layer having a dielectric constant greater than 10 is disposed on the front side of the at least one electrode element, wherein the insulating material layer has a front side. and A graphite sheet, the graphite sheet being disposed on the front side of the insulating material layer. The plurality of temperature sensors are positioned in front of the graphite layer.

12. The apparatus according to claim 1, further comprising: A graphite sheet is disposed in front of the plurality of temperature sensors such that when the support holds the at least one electrode element near the subject's body, the graphite sheet will be positioned between the plurality of temperature sensors and the subject's body; and A conductive adhesive layer is disposed in front of the graphite sheet such that when the support holds the at least one electrode element near the subject's body, the conductive adhesive layer is positioned between the graphite sheet and the subject's body.

13. The apparatus of claim 1, further comprising a flexible circuit, the flexible circuit including an insulating substrate and a plurality of conductive traces. The at least one electrode element comprises multiple electrode elements. The flexible circuit is positioned such that when the support holds the plurality of electrode elements near the subject's body, the flexible circuit is positioned between the front surfaces of the plurality of electrode elements and the subject's body. The plurality of temperature sensors are attached to the flexible circuit, and The multiple conductive traces of the flexible circuit are configured to provide an electrical interface with the multiple temperature sensors.

14. The apparatus of claim 13, wherein each of the temperature sensors comprises a thermistor.

15. The apparatus of claim 13, wherein the flexible circuit is shaped and sized to cover less than 10% of the sum of the areas of all the electrode elements.

16. The apparatus of claim 13, wherein the sum of the areas of all the electrode elements is at least 10 cm².

17. A method for applying an alternating electric field to the body of a subject, the method comprising: At least one first electrode element is positioned against the subject's body, wherein a plurality of first temperature sensors are sandwiched between the at least one first electrode element and the subject's body such that the first temperature sensors are in thermal contact with the subject's body, wherein each of the at least one first electrode element has a corresponding rear surface; Position the first heat exchanger in thermal contact with the rear surface of the at least one first electrode element; At least one second electrode element is positioned against the subject's body, wherein a plurality of second temperature sensors are sandwiched between the at least one second electrode element and the subject's body such that the second temperature sensors are in thermal contact with the subject's body, wherein each of the at least one second electrode element has a corresponding rear surface; Position the second heat exchanger in thermal contact with the rear surface of the at least one second electrode element; An alternating voltage is applied between the at least one first electrode element and the at least one second electrode element; A first cooling fluid is passed through the first heat exchanger to remove heat from the at least one first electrode element; A second cooling fluid is passed through the second heat exchanger to remove heat from the at least one second electrode element; Multiple first temperatures are determined based on the outputs of the multiple first temperature sensors; Multiple second temperatures are determined based on the outputs of the multiple second temperature sensors; Based on the determined plurality of first temperatures, at least one of the following is adjusted: (a) the amplitude of the AC voltage, and (b) the transfer of the first cooling fluid through the first heat exchanger; and Based on the determined plurality of second temperatures, at least one of the following is adjusted: (i) the magnitude of the AC voltage, and (ii) the transfer of the second cooling fluid through the second heat exchanger.

18. The method of claim 17, wherein the at least one first electrode element comprises a plurality of first electrode elements, and wherein each of the plurality of first temperature sensors is sandwiched between a corresponding first electrode element of the plurality of first electrode elements and the subject's body; and The at least one second electrode element comprises a plurality of second electrode elements, and each of the plurality of second temperature sensors is sandwiched between a corresponding second electrode element of the plurality of second electrode elements and the subject's body.

19. The method of claim 17, wherein each of the first temperature sensors and each of the second temperature sensors comprises a thermistor.

20. A kit for applying an alternating electric field to the body of a subject, the kit comprising: The first component includes: Multiple electrode elements, wherein each of the electrode elements has a corresponding front side, and the front side has a corresponding area; and A support member configured to hold the plurality of electrode elements near the subject's body such that the front faces of the plurality of electrode elements face the subject's body; and The second component includes: A flexible circuit, comprising an insulating substrate and multiple conductive traces; and Multiple temperature sensors are attached to the flexible circuit. The multiple conductive traces of the flexible circuit are configured to provide an electrical interface with the multiple temperature sensors, and The flexible circuit is configured to fit between the front of the plurality of electrode elements and the subject's body when the support holds the plurality of electrode elements near the subject's body.

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