Varying Metallization Coverage on Individual Electrode Elements in Tumor Treating Fields (TTFields) to Maximize Current Without Overheating

Abstract

Conventional transducer arrays for applying tumor treating electric fields (TTFields) include a set of individual electrode elements, with the more peripherally located electrode elements (e.g., electrode elements at the corners or edges of the transducer array) tending to become hotter than the more centrally located electrode elements. This situation can be improved by reducing the capacitance of the more peripherally located electrode elements. Reducing the capacitance of those elements reduces the current through those elements (at any given voltage), which reduces their temperature. When the capacitance of the more peripherally located electrode elements is reduced, a higher voltage can be used without overheating. This results in an increase in overall current, which can improve the effectiveness of TTFields treatment.

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of U.S. Application No. 63 / 083,590, filed September 25, 2020, the entire disclosure of which is incorporated herein by reference in its entirety. [Background technology]

[0002] U.S. Patent Nos. 7,136,699 and 7,146,210, each incorporated herein by reference, describe treating tumors or other rapidly dividing cells with AC electric fields at particular frequencies and field strengths. These AC electric fields are referred to herein as "Tumor Treating Fields" or "TTFields."

[0003] U.S. Patent No. 8,715,203 describes a prior art "composite electrode" (also referred to as a "transducer array") used to apply TTFields. The transducer array of the '203 patent is shown in FIG. 1 and comprises nine circular electrode elements, each comprising a ceramic element (e.g., a ceramic disk) approximately 2 cm in diameter. One side of each ceramic element faces the subject's skin, and the other side has a conductive backing (e.g., silver-plated). A flex circuit connects all of the silver-plated back surfaces of the ceramic elements in any given transducer array to a single lead wire. A layer of hydrogel is placed between each of the ceramic elements and the subject's skin.

[0004] When a first transducer array is positioned against the person's skin on one side of the person's body and a second transducer array is positioned against the person's skin on the opposite side of the person's body and an AC voltage is applied between the leads of the first transducer array and the leads of the second transducer array, a current is capacitively coupled into the person's body. For TTFields to be effective, a sufficient current must be capacitively coupled through the electrodes into the person's body, with higher currents being strongly correlated with greater therapeutic efficacy. Because increasing the capacitance of each transducer array results in a corresponding increase in current, prior art transducer arrays have typically used relatively thin ceramic elements (e.g., ceramic discs about 1 mm thick) with very high dielectric constants (e.g., greater than 1000) to achieve sufficiently high currents.

[0005] The ceramic elements heat up during use and safety reasons require that the temperature at each of the ceramic elements remains below a certain safety threshold (eg, 41°C).

[0006] When the ceramic elements in any given transducer array are wired in parallel, if the temperature in any one of the ceramic elements in a given transducer array becomes too high, the voltage applied to the entire transducer array must be reduced to prevent the temperature of the hottest element from exceeding a safety threshold. (In the '203 patent, temperature readings are obtained using multiple thermistors, each positioned at the center of a respective ceramic element.) For example, assume that the temperature of only one of the ceramic elements in the prior art system of FIG. 1 rises to 41°C, while the temperature of the remaining eight ceramic elements is only 39°C. In this situation, even though the average temperature of the electrode elements is ((8 x 39) + 41) / 9 = 39.2°C, the voltage applied to the transducer array must be reduced to prevent the hottest element from overheating. This reduction in voltage results in a reduction in current, which can reduce the effectiveness of the treatment. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] U.S. Patent No. 7,136,699 [Patent Document 2] U.S. Patent No. 7,146,210 [Patent Document 3] U.S. Patent No. 8,715,203 Summary of the Invention [Means for solving the problem]

[0008] One aspect of the present invention is directed to a first device for applying an alternating current electric field to a living subject. The first device includes a plurality of conductive regions, a plurality of regions of dielectric material, a substrate, and at least one electrical conductor. Each of the conductive regions has a front surface and a respective area. Each of the regions of dielectric material has (i) a respective front surface and (ii) a respective rear surface positioned opposite the front surface of a respective one of the conductive regions. The substrate is configured to hold the front surfaces of the plurality of regions of dielectric material on or within the subject's body and support the plurality of conductive regions at respective locations distributed around the center of gravity. The at least one electrical conductor is positioned in electrical contact with the plurality of conductive regions. The plurality of conductive regions includes at least one first conductive region and a plurality of second conductive regions, each of which is positioned more peripherally relative to the center of gravity than the at least one first conductive region. The area of ​​each of the second conductive regions is at least 10% smaller than the area of ​​each of the first conductive regions.

[0009] In some embodiments of the first apparatus, each of the regions of dielectric material comprises a ceramic disc and each of the plurality of conductive regions comprises a layer of metal disposed on a rear surface of a respective one of the ceramic discs. In some embodiments of the first apparatus, each of the regions of dielectric material comprises a flat ceramic material and each of the plurality of conductive regions comprises a layer of metal disposed on a rear surface of a respective one of the ceramic material.

[0010] In some embodiments of the first apparatus, each of the plurality of conductive regions comprises a printed circuit pad and each of the regions of dielectric material comprises a polymer film. In some embodiments of the first apparatus, each of the plurality of conductive regions comprises a printed circuit pad and each of the regions of dielectric material is implemented using different sections of a single continuous polymer film. In some embodiments of the first apparatus, each of the plurality of conductive regions comprises a layer of metal foil and each of the regions of dielectric material comprises a polymer film. In some embodiments of the first apparatus, each of the plurality of conductive regions comprises a layer of metal foil and each of the regions of dielectric material is implemented using different sections of a single continuous polymer film.

[0011] Some embodiments of the first device further comprise an adhesive layer configured to hold the substrate against a person's skin such that the front surface of the plurality of regions of dielectric material faces the subject's body.

[0012] In one embodiment of the first device, the plurality of conductive regions comprises at least one first conductive region, a plurality of second conductive regions, and a plurality of third conductive regions, each of the third conductive regions being positioned more peripherally with respect to the center of gravity than the plurality of second conductive regions, and the extent of each of the third conductive regions being at least 10% smaller than the extent of each of the second conductive regions, and each of the second conductive regions being positioned more peripherally with respect to the center of gravity than the at least one first conductive region, and the extent of each of the second conductive regions being at least 10% smaller than the extent of each of the first conductive regions.

[0013] Another aspect of the present invention is directed to a second device for applying an alternating current electric field to a living subject. The second device includes a plurality of conductive regions, a plurality of regions of dielectric material, a substrate, a plurality of temperature sensors, and at least one electrical conductor. Each of the conductive regions has a front surface and a respective area. Each of the regions of dielectric material has (i) a respective front surface and (ii) a respective rear surface positioned opposite the front surface of a respective one of the conductive regions. The substrate is configured to hold the front surfaces of the plurality of regions of dielectric material on or within the subject's body and support the plurality of conductive regions at respective locations distributed around the center of gravity. Each of the temperature sensors is positioned in thermal contact with a respective region of the dielectric material. The at least one electrical conductor is positioned in electrical contact with the plurality of conductive regions. The plurality of conductive regions includes at least one first conductive region and a plurality of second conductive regions, each of which is positioned more peripherally relative to the center of gravity than the at least one first conductive region. The capacitance associated with each of the second conductive regions is at least 10% less than the capacitance associated with each of the first conductive regions.

[0014] In some embodiments of the second device, each of the second conductive regions has an extent that is at least 10% less than each of the first conductive regions. In some embodiments of the second device, the region of dielectric material disposed opposite a front surface of each of the second conductive regions is at least 10% thicker than the region of dielectric material disposed opposite a front surface of each of the first conductive regions. In some embodiments of the second device, the region of dielectric material disposed opposite a front surface of each of the second conductive regions has a dielectric constant that is at least 10% less than the region of dielectric material disposed opposite a front surface of each of the first conductive regions.

[0015] Another aspect of the present invention is directed to a third device for applying an alternating current electric field to a biological subject. The third device includes a flex circuit, at least one first flexible polymer region, and a plurality of second flexible polymer regions. The flex circuit includes: (a) at least one first conductive pad positioned on a front side of the flex circuit, each having a first extent; (b) a plurality of second conductive pads positioned on the front side of the flex circuit at locations peripheral to the at least one first conductive pad, each having a respective extent at least 10% less than the first extent; and (c) at least one conductive trace disposed in electrical contact with the at least one first conductive pad and the plurality of second conductive pads. The at least one conductive trace is disposed such that each of the first conductive pads and each of the second conductive pads can be driven by an electrical signal. Each of the first flexible polymer regions has a front surface, and each of the at least one first flexible polymer region is disposed on and in front of a respective one of the first conductive pads on the front side of the flex circuit. Each of the second flexible polymer regions has a front surface, and is disposed on and in front of a respective one of the second conductive pads on the front side of the flex circuit. At at least one frequency between 100 kHz and 500 kHz, each of the polymer regions has a dielectric constant of at least 20, and each of the polymer regions has a thickness of less than 20 μm in a direction perpendicular to its front surface.

[0016] Some embodiments of the third device further include a plurality of thermistors positioned on the rear side of the flex circuit, wherein each of the plurality of thermistors is disposed in thermal contact with a respective one of the plurality of second conductive pads, and the flex circuit further includes a plurality of conductive traces providing access to the plurality of thermistors.

[0017] Some embodiments of the third device further include a flexible third layer and a layer of conductive hydrogel. In these embodiments, the flexible third layer is configured to support the flex circuit. The flexible third layer has a front surface. A first portion of the front surface of the flexible third layer is coated with an adhesive that adheres to and is easily removable from a person's skin. The first portion is positioned outwardly relative to the flex circuit such that when the first portion is pressed against an area of ​​skin, the adhesive in the first portion adheres to the skin and holds the plurality of second flexible polymer regions adjacent to the skin. A layer of conductive hydrogel is disposed on the front surface of each of the first flexible polymer regions and on the front surface of each of the second flexible polymer regions, the hydrogel being positioned to contact the skin when each of the second flexible polymer regions is held adjacent to the skin by the adhesive.

[0018] In some embodiments of the third device, each of the polymer regions has a thickness of less than 5 μm. In some embodiments of the third device, each of the second conductive pads comprises a plurality of conductive subregions interconnected by severable conductive links.

[0019] An embodiment of the third device further includes a flexible third layer, a layer of conductive hydrogel, and a plurality of thermistors. The flexible third layer is configured to support the flex circuit. The flexible third layer has a front surface. A first portion of the front surface of the flexible third layer is coated with an adhesive that adheres to and is easily removable from a person's skin. The first portion is positioned outwardly relative to the flex circuit such that when the first portion is pressed against an area of ​​skin, the adhesive in the first portion adheres to the skin and holds the plurality of second flexible polymer regions adjacent to the skin. A layer of conductive hydrogel is disposed on the front surface of each of the first and second flexible polymer regions, and the hydrogel is positioned to contact the skin when each of the second flexible polymer regions is held adjacent to the skin by the adhesive. The plurality of thermistors are positioned on the rear side of the flex circuit, each of the plurality of thermistors being disposed in thermal contact with a respective one of the plurality of second conductive pads. The flex circuit further includes a plurality of conductive traces providing access to the plurality of thermistors. Optionally, in these embodiments, each of the polymer regions has a thickness of less than 5 μm. [Brief explanation of the drawings]

[0020] [Figure 1] FIG. 1 is a diagram of a prior art transducer array for delivering TTFields. [Figure 2] FIG. 1 is a diagram of a layout for a first embodiment of a transducer array in which the capacitance of the four corner elements is smaller than the capacitance of more centrally located elements. [Figure 3] 1A-1C are diagrams of three different approaches to reducing capacitance by varying the extent of conductive metallization on the backside of a set of dielectric ceramic elements. [Figure 4] FIG. 10 is a diagram of a layout for a second embodiment of a transducer array in which the capacitance of the six edge elements is smaller than the capacitance of the more centrally located elements. [Figure 5A]FIG. 1 is a front view of an embodiment using a flex circuit to implement a transducer array. [Figure 5B] FIG. 1 is a side (cross-sectional) view of one embodiment using a flex circuit to implement a transducer array. [Figure 6A] FIG. 10 is a front view of another embodiment using a flex circuit to implement a transducer array. [Figure 6B] FIG. 10 is a side (cross-sectional) view of another embodiment using a flex circuit to implement a transducer array. [Figure 6C] FIG. 10 is an exploded view of another embodiment using a flex circuit to implement a transducer array. [Figure 7A] FIG. 10 is a front view of another embodiment using a flex circuit to implement a transducer array. [Figure 7B] FIG. 10 is a side (cross-sectional) view of another embodiment using a flex circuit to implement a transducer array. [Figure 8] FIG. 1 is a diagram of a technique for reducing capacitance by reducing the area of ​​a PCB pad (or metal) that serves as a plate of a capacitor by incorporating voids into the PCB pad (or metal). [Figure 9] FIG. 1 is a diagram of a PCB pad layout that provides lower capacitance for pads located more peripherally. [Figure 10] FIG. 10 illustrates an alternative approach to reducing capacitance in specific areas of a flex circuit by severing thin conductive links. DETAILED DESCRIPTION OF THE INVENTION

[0021] Various embodiments are described in detail below with reference to the accompanying drawings, in which like numerals represent like elements.

[0022] The electrode elements in the transducer arrays used to deliver TTFields to the patient's body can overheat during use, requiring a reduction in voltage to avoid exceeding a temperature safety threshold (approximately 41°C), resulting in a reduction in current that can reduce the effectiveness of the treatment.

[0023] One factor that can cause overheating of any given element is a poor connection between the element and the subject's skin, which can occur, for example, if the hydrogel between the electrode element and the skin dissolves or becomes detached from the skin as a result of poor tape adhesion, etc. However, after examining the temperature data captured from the nine-element 3x3 transducer array, the inventors realized that another factor was also at play.

[0024] More specifically, the inventors obtained temperature data from 80 prior art transducer arrays when they were used to apply TTFields to 20 randomly selected human subjects. Each transducer array had nine ceramic elements arranged in a 3 x 3 array, and the structure of all ceramic elements in any given transducer array was identical. The data included temperature measurements (obtained using thermistors integrated into the transducer array) from individual ceramic elements within each transducer array. The temperature measurement data was analyzed to determine which ceramic element in any given transducer array reached 41.1°C first (in this case, a voltage drop was required to prevent that element from overheating). This analysis revealed that 90% of the time, the first ceramic element to reach 41.1°C was one of the four corner elements. Notably, the temperature difference between the hottest and coolest elements in these cases was typically between 3°C and 5°C. Computer simulations also suggest that the current flowing through the corner elements is higher than that of the non-corner elements.

[0025] The temperature measurement data was also analyzed to find the mean temperature and standard deviation for each disk location. This analysis revealed that the mean temperature for the four corner elements was 37.84°C (standard deviation = 1.32, N = 639,413 temperature readings), while the mean temperature for all non-corner elements was 37.14°C (standard deviation = 1.15, N = 641,708 temperature readings). This means that, on average, the four corner elements were operating 0.7°C hotter than the non-corner elements measured.

[0026] The inventors have recognized that electrode elements at the corners / edges of an array operating at higher temperatures than non-corner elements are problematic because when corner elements operate at higher temperatures, they reduce the maximum current that can be delivered by a given transducer array (which can limit the effectiveness of the treatment).

[0027] The embodiments described herein offset the average predicted temperature rise of the electrode elements in a given transducer array by proactively reducing the current flowing through the corner / edge elements of each transducer array (compared to the current flowing through more central elements) to proactively reduce the temperature rise of the corner / edge elements. Notably, this reduction in current is not achieved by increasing the ohmic resistance of the corner / edge elements (I 2 (This causes heating of R.) Instead, the reduction in current is achieved by reducing the capacitance of the corner / edge elements (compared to the capacitance of more centrally located elements).

[0028] The present invention may be understood more readily with reference to the following detailed description, examples, drawings, and claims, as well as their preceding and following descriptions. It is to be understood, however, that the invention is not, unless expressly stated otherwise, limited to the particular apparatus, devices, systems, and / or methods disclosed, as such may, of course, vary.

[0029] Headings are provided for convenience only and should not be construed as limiting the invention in any way. Embodiments illustrated under any heading or in any portion of this disclosure may be combined with embodiments illustrated under the same or any other heading or in any other portion of this disclosure.

[0030] Any combination of the elements described herein in all possible variations thereof is covered by the invention unless otherwise expressly stated herein or otherwise clearly contradicted by context.

[0031] As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0032] FIG. 2 depicts a layout for a first embodiment of a transducer array 200, in which nine circular elements A1-A9 made of a dielectric material (e.g., ceramic elements) are arranged in a 3x3 array and supported by a substrate 250. The centroids of all of the elements A1-A9 are labeled "C," and the substrate 250 supports the elements at respective locations distributed around the centroids. In this embodiment, the capacitance of the four corner elements (i.e., A1, A3, A7, and A9, marked with asterisks) is smaller than the capacitance of the more centrally located elements A2, A4, A5, A6, and A8. The back surface of each of the elements A1-A9 has a conductive coating (e.g., metalized or silver-plated), and the front of each of the elements A1-A9 is positioned to face the subject during use. Preferably, a layer of hydrogel is disposed between the front surface of each of the elements and the subject's skin during use.

[0033] One or more electrical conductors (e.g., wires or traces in a flex circuit, not shown) couple to the metallized backside of each of elements A1-A9. Preferably, the wires are configured so that the metallized backside is electrically coupled to a single conductive wire or trace, meaning that all of the capacitances of elements A1-A9 are arranged in parallel. A temperature sensor (e.g., a thermistor, not shown) is preferably positioned in thermal contact with some or all of elements A1-A9, similar to how thermistors are positioned in the prior art. The thermal contact between the temperature sensor and the elements can be direct or indirect.

[0034] As in the prior art, when a first transducer array 200 is positioned against a person's skin on one side of the person's body and a second transducer array 200 is positioned against a person's skin on an opposite side of the person's body and an AC voltage is applied between the leads of the first and second transducer arrays, current is capacitively coupled into the person's body. However, the embodiment of Figure 2 differs from the prior art because the capacitance of corner elements A1, A3, A7, and A9 (which are positioned more peripherally with respect to the center of gravity C) is less than the capacitance of the more centrally positioned elements A2, A4, A5, A6, and A8.

[0035] The capacitance of any given ceramic element is proportional to (a) the extent of metallization / silver plating on the backside of the ceramic element, (b) the dielectric constant of the ceramic element, and (c) inversely proportional to the thickness of the ceramic element. Any of these three parameters can be varied to reduce the capacitance of a corner element compared to the capacitance of other elements. The ceramic element may have a flat, uniform surface, although in alternative embodiments, the ceramic element may not be flat.

[0036] FIG. 3 depicts three different approaches for reducing the capacitance of the corner elements in FIG. 2 by varying the extent of the conductive metallization on the back side of the dielectric ceramic element. More specifically, the top left panel in FIG. 3 depicts the extent of the metallization pattern 212 on ceramic element 210 for center elements A2, A4, A5, A6, and A8 in FIG. 2. The next panel in FIG. 3 depicts metallization pattern 222 on element 220, which has a smaller extent than metallization pattern 212. Because metallization pattern 222 on element 220 has a smaller diameter than metallization pattern 212, the capacitance provided by element 220 is smaller than the capacitance of element 210. Note that if metallization pattern 222 is smaller, the diameter of ceramic element 220 may optionally be reduced.

[0037] The next panel in FIG. 3 depicts a different metallization pattern 232 on element 230, which has a smaller extent than metallization pattern 212. Both metallization patterns 232 and 212 have the same diameter, but because metallization pattern 232 has a circular void 235, the extent of metallization pattern 232 is smaller than the extent of metallization pattern 212. As a result, the capacitance provided by element 230 is smaller than the capacitance of element 210. Similarly, the bottom panel in FIG. 3 depicts yet another metallization pattern 242 on element 240, which has a smaller extent than metallization pattern 212. Both metallization patterns 242 and 212 have the same diameter, but because metallization pattern 242 has a rectangular void 245, the extent of metallization pattern 242 is smaller than the extent of metallization pattern 212. As a result, the capacitance provided by element 240 is smaller than the capacitance of element 210.

[0038] 3 can be used to create the transducer array depicted in FIG. 2 by using metallization layout 212 for center elements A2, A4, A5, A6, and A8, and using any one of metallization layouts 222, 232, 242 for corner elements A1, A3, A7, and A9 to provide smaller capacitance at the corner elements. For example, to reduce the capacitance of the corner elements by 10%, the metallization coverage at those elements should be reduced by 10%.

[0039] Alternatively, the capacitance of the corner elements may be reduced (relative to the capacitance of the central element) by keeping the metallization area constant and using thicker ceramic elements at the four corners. For example, to reduce the capacitance of the corner elements by 10%, the thickness of the ceramic elements at the corners should be 10% greater than the thickness of the central ceramic elements.

[0040] As yet another alternative, the capacitance in the corner elements may be reduced (relative to the capacitance of the center element) by holding the metallization coverage constant and using ceramic elements with smaller dielectric constants at the four corners. For example, to reduce the capacitance of the corner elements by 10%, the dielectric constant of the ceramic elements at the corners should be 10% less than the dielectric constant of the center ceramic element.

[0041] As yet another alternative, the capacitance in the corner elements may be reduced (relative to the capacitance of the central element) by using elements whose capacitance is customizable after the date of the element's original manufacture. In this approach, each element is initially manufactured with one or more sub-regions 266 connected to a main region 262 by thin, severable conductive links 268. In the element's initial state, the area of ​​the metallization of the element is the sum of the areas of the main region 262 and the sub-regions 266.

[0042] At some point after the initial fabrication of the elements, the capacitance of the corner elements is reduced by severing the conductive links 268. Severing the links 268 can be accomplished using a variety of alternative techniques, such as, for example, breaking the links 268 with a laser or passing a sufficiently high current through the links 268 (similar to blowing a fuse). After those links are severed, the corresponding subregions 266 in the corner elements are effectively disconnected from the circuit, which reduces the active area of ​​the corner elements. Also, because the conductive links 268 for the center elements are not severed, the center elements will have a larger active area (and correspondingly larger capacitance) than the corner elements.

[0043] Returning to FIG. 2 , assume that a first transducer array 200 is positioned against the person's skin on one side of the person's body, a second transducer array 200 is positioned against the person's skin on the opposite side of the person's body, and an AC voltage is applied between the leads of the first transducer array and the leads of the second transducer array. Further, assume that the capacitance of corner elements A1, A3, A7, and A9 is 10% less than the capacitance of center elements A2, A4, A5, A6, and A8. (The reduction in capacitance can be achieved using any of the techniques described above.) In this situation, the current coupled through the corner elements will be approximately 10% less than the current if the capacitance of the corner elements were the same as the capacitance of the center elements. This reduction in current in the corner elements will also reduce the temperature of the corner elements.

[0044] We now analyze the benefits derived from reducing the capacitance of corner elements. For comparison purposes, we begin by looking at a prior art situation in which all elements are driven by an AC voltage with amplitude X and all elements in a transducer array have the same capacitance. Assume that during operation, the corner elements of the prior art transducer array reach a temperature of 41°C, while the non-corner elements only have a temperature of 39°C. Under these circumstances, the corner elements handle the highest possible current without overheating. However, the non-corner elements, operating below 41°C, necessarily handle less current than they can safely handle without overheating.

[0045] Now assume a situation where all elements are driven by an AC voltage with the same amplitude X, but the capacitance of a corner element in the transducer array is reduced by whatever percentage is necessary to reduce the temperature of the corner element by 2° C. Under these conditions, all of the elements in the transducer array 200 will operate at 39° C., which means that all of the elements will handle less current than they can safely handle without overheating.

[0046] Because all of the elements handle less current than they can safely handle, the voltage amplitude can be increased beyond X to any amplitude that raises the temperature of the corner elements to 41°C. At this point, the corner elements will handle the same current they handled in the prior art situation described above. However, the non-corner elements in the embodiment of FIG. 2 will handle a larger current than the non-corner elements in the prior art situation because they are now driven by a higher voltage. This means that the total current handled by the transducer array of FIG. 2 (i.e., the sum of the currents handled by the corner and non-corner elements) will be greater than the total current handled in the prior art situation. This increase in current can also improve the effectiveness of the treatment.

[0047] FIG. 4 depicts a layout for a second embodiment transducer array 200′ in which thirteen circular elements B1-B13 made of a dielectric material (e.g., ceramic elements) are arranged in three rows and supported by a substrate 250. The centroids of all elements B1-B13 are labeled “C,” and the substrate 250 supports the elements at respective locations distributed around the centroids. The structure and use of the embodiment of FIG. 4 is similar to that of the previously described embodiment of FIG. 2, except that in the embodiment of FIG. 4, the capacitance of the six edge elements (i.e., B1, B4, B5, B9, B10, and B13, marked with asterisks) is less than the capacitance of the more centrally located elements B2, B3, B6-B8, B11, and B12. Any of the techniques previously described for reducing the limiting capacitance of corner elements in the embodiments of FIGS. 2 and 3 can be used to reduce the capacitance of edge elements in a given row in the embodiment of FIG. 4. For each of these approaches, the current can be balanced by controlling the capacitance of each electrode element or by varying the capacitance of groups of electrode elements in a given array, which may be achieved using two, three, four or more different groups of electrode elements.

[0048] Reducing the capacitance of the end elements in any given row results in a corresponding reduction in current, which will reduce the temperature of the end elements (compared to a transducer array in which all elements have the same capacitance). The benefits derived from reducing the capacitance of the end elements in this embodiment of Figure 4 are similar to the benefits derived from reducing the capacitance of the corner elements in the embodiment of Figure 2.

[0049] While circular ceramic dielectric materials having a layer of metal disposed on their rear surface serve as electrode elements in the previously described embodiments of Figures 2-4, it should be noted that the electrode elements need not be circular and alternative shapes (e.g., flat square or hexagonal ceramic dielectric materials) may be used.

[0050] Furthermore, the previously described techniques for reducing the capacitance of electrode elements at the corners of a transducer array (see, e.g., FIG. 2) or at the ends of each column of a transducer array (see, e.g., FIG. 4) are not limited to electrode elements constructed using a ceramic dielectric material having a layer of metal disposed on its rear surface. To the contrary, the techniques for reducing the capacitance of electrode elements at the corners of a transducer array or at the ends of each column of a transducer array can be applied to transducer arrays made using a variety of alternative structures.

[0051] Some examples of alternative approaches to constructing transducer arrays will now be described in relation to Figures 5-7, followed by a description of how the capacitance of corner / edge elements can be changed when these variations of the transducer array are used.

[0052] The embodiments described below in connection with Figures 5-7 rely on recently discovered polymer compositions that have significantly higher dielectric constants than conventional polymers. More specifically, the dielectric constants of these recently discovered polymer compositions are large enough to create transducer arrays that can effectively capacitively couple AC signals through a polymer insulating layer into a person's body. Note that in all embodiments described herein, the front of the electrode or transducer array is the side that faces the person's body, and the back of the electrode or transducer array is the opposite side.

[0053] 5A and 5B depict front and side (cross-sectional) views of an embodiment using a flex circuit to implement a transducer array. This embodiment is used to apply TTFields to a living subject. The embodiment of FIG. 5 has a flex circuit with a plurality of conductive pads 20 (e.g., copper pads) positioned on the front side of the flex circuit 25. Each of the conductive pads 20 has an area. At least one conductive trace (not shown) is disposed in electrical contact with the plurality of conductive pads 20. The at least one conductive trace is positioned such that each of the conductive pads 20 can be driven by an electrical signal.

[0054] This embodiment also has a plurality of flexible polymer regions 30. These flexible polymer regions 30 may be regions within a single continuous sheet of polymer material, as depicted in FIG. 5A. Alternatively, these regions 30 may be separate areas (or "islands") of flexible polymer separated by gaps. Each of the flexible polymer regions 30 has a front surface and is disposed on and in front of a respective one of the conductive pads 20 on the front side of the flex circuit 25.

[0055] The specifications for the polymer regions 30 in this embodiment are as follows: (1) at least one frequency between 100 kHz and 500 kHz, each of the polymer regions 30 has a dielectric constant of at least 20, and (2) each of the polymer regions 30 has a thickness perpendicular to its front surface of less than 20 μm. In some embodiments, the thickness of each of the polymer regions 30 multiplied by its dielectric strength is at least 50 V, and in some embodiments, this value is at least 200 V. For example, if the thickness is 10 μm and the dielectric strength is 30 MV / m, this value is 300 V.

[0056] In certain preferred embodiments, the polymer region 30 comprises poly(vinylidene fluoride-trifluoroethylene-chlorotrifluoroethylene) and / or poly(vinylidene fluoride-trifluoroethylene-1-chlorofluoroethylene). These two polymers are abbreviated herein as "poly(VDF-TrFE-CtFE)" and "poly(VDF-TrFE-CFE)," respectively. These embodiments are particularly advantageous because the dielectric constants of these materials are on the order of 40. Because the TTFields are capacitively coupled through the electrodes 10, and because capacitance is inversely proportional to the thickness of the dielectric layer, the polymer region 30 is preferably made as thin as possible (e.g., less than 10 μm or less than 5 μm). On the other hand, the polymer region 30 should not be too thin, as this may impair manufacturability, compromise the structural integrity of the layer, or risk dielectric breakdown when an AC signal is applied. In certain embodiments, the polymer region 30 has a thickness that is at least 1 μm. In some embodiments, polymer region 30 is between 1 and 5 μm thick, or between 1 and 3 μm thick (e.g., about 2 μm), which provides a good balance between the parameters noted above. In some embodiments, polymer region 30 has a uniform thickness. However, in alternative embodiments (e.g., as described below), the thickness may be non-uniform.

[0057] Optionally, ceramic nanoparticles may be mixed into poly(VDF-TrFE-CtFE) and / or poly(VDF-TrFE-CFE) to form a "nanocomposite." Optionally, these ceramic nanoparticles may include ferroelectric metal oxides (e.g., barium titanate and barium strontium titanate).

[0058] In alternative embodiments, instead of forming the polymer region 30 from poly(VDF-TrFE-CtFE) and / or poly(VDF-TrFE-CFE), different polymers that provide high levels of capacitance may be used. The requirements for these different polymers are as follows: (1) the polymer layer must have a dielectric constant of at least 20 at at least one frequency between 100 kHz and 500 kHz; and (2) the polymer layer must have a thickness of less than 20 μm in a direction perpendicular to the front surface of the polymer layer. In some embodiments, the thickness of the polymer layer multiplied by its dielectric strength is at least 50 V, and in some embodiments, this value is at least 200 V. Note that the values ​​for dielectric constant and breakdown voltage specified herein are specified within a temperature range of 30-42° C., and that values ​​for these parameters outside that temperature range are less relevant.

[0059] Examples of alternative polymers that can be used in place of poly(VDF-TrFE-CtFE) and / or poly(VDF-TrFE-CFE) include: (1) ceramic nanoparticles mixed into at least one of poly(VDF-TrFE), P(VDF-HFP), PVDF, or other polymers; and (2) barium titanate and / or barium strontium titanate ceramic nanoparticles mixed into at least one of poly(VDF-TrFE), P(VDF-HFP), PVDF, where poly(VDF-TrFE), P(VDF-HFP), and PVDF are poly(vinylidene fluoride-trifluoroethylene), poly(vinylidene fluoride-hexafluoropropylene), and polyvinylidene fluoride, respectively. In other embodiments, polymer region 30 is formed by mixing ceramic nanoparticles into at least one other polymer (i.e., a polymer not previously listed in this paragraph).

[0060] 5 embodiment, the polymer regions 30 can be printed, sprayed, or cast directly onto the conductive pads 20, which makes it very easy to obtain very thin polymer layers. In some embodiments (e.g., embodiments in which the polymer regions 30 are printed, sprayed, or cast directly onto the conductive pads 20), the polymer regions have a thickness of less than 5 μm.

[0061] Increasing the total area covered by the conductive pads 20 increases the capacitance of the entire device. In one embodiment, the area of ​​the multiple conductive pads 20 totals at least 25 cm 2 becomes.

[0062] The embodiments of FIG. 5 can be secured to a person's skin using a flexible third layer, similar to a bandage. In these embodiments, the flexible third layer 40 is positioned behind the flex circuit 25. The flexible third layer 40 has a front surface. At least a portion of the front surface of the third layer 40 is covered with an adhesive. A first region of adhesive is positioned directly behind and supports the flex circuit 25, and a second region of adhesive is positioned outward relative to the first region (this is the portion not covered by the flex circuit in FIG. 5A). This second region is configured to adhere to the skin when pressed against an area of ​​skin and hold the plurality of polymer regions 30 adjacent to the skin. The adhesive used in the second region must also be easily removable from the skin. Although the flexible third layer 40 holds the plurality of polymer regions 30 adjacent to the skin, a layer of conductive hydrogel 50 may be interposed between the polymer regions 30 and the skin and still be considered an "adjacent" relationship between the polymer regions 30 and the skin. (This applies to the embodiment of FIG. 5 as well as other embodiments described herein.) In this situation, the layer of hydrogel 50 is disposed in front of each of the polymer regions 30. The hydrogel 50 is positioned to contact the skin when each of the polymer regions 30 is held adjacent to the skin by the second region of adhesive.

[0063] Variations on the embodiment of FIG. 5 use a different approach to holding the polymer regions 30 adjacent to the skin using a flexible third layer. In these embodiments, the flexible third layer is configured to support a flex circuit. The flexible third layer has a front surface and may optionally include multiple cut-out open areas corresponding to the locations of the conductive pads 20. A first portion of the front surface of the flexible third layer is coated with an adhesive that adheres to and is easily removable from a person's skin. The first portion is positioned outwardly relative to the flex circuit 25 so that when the first portion is pressed against an area of ​​skin, the adhesive in the first portion adheres to the skin and holds the multiple polymer regions 30 adjacent to the skin. As in the previous embodiment, a layer of conductive hydrogel 50 may be disposed on the front surface of each of the polymer regions 30. The hydrogel 50 is positioned to contact the skin when each of the polymer regions 30 is held adjacent to the skin by the adhesive.

[0064] Multiple thermistors can be incorporated into this embodiment of Figure 5. One way to accomplish this is to position multiple thermistors 60 on the back side of the flex circuit 25 (i.e., between the flex circuit 25 and the flexible third layer 40), with each of the multiple thermistors 60 positioned in thermal contact with a respective one of the multiple conductive pads 20. In these embodiments, the flex circuit 25 further includes multiple conductive traces that provide access to the multiple thermistors 60. In an alternative embodiment (not shown), the thermistor 60 may be positioned between the conductive pads 20. In this case, however, additional insulation should be provided in front of the thermistor.

[0065] Figures 6A, 6B, and 6C show front, side (cross-sectional), and exploded views of another embodiment that uses a flex circuit to implement a transducer array. This embodiment is also used to apply TTFields to a living subject. However, instead of using conductive pads integrated into the flex circuit (as in the previously described embodiment of Figure 5), the embodiment of Figure 6 relies on multiple metal foils positioned in front of the flex circuit and electrically coupled to respective pads on the flex circuit.

[0066] The embodiment of Figure 6 has (a) a plurality of conductive pads 140 positioned on the front side of a flex circuit 145, and (b) at least one conductive trace (not shown) disposed in electrical contact with the plurality of conductive pads 140. The at least one conductive trace is positioned such that each of the conductive pads 140 can be driven by an electrical signal. A plurality of metal foils 120 are positioned in front of the flex circuit 145, each of the metal foils 120 having a front surface with an area. Each of the metal foils 120 is electrically coupled to a respective one of the conductive pads 140.

[0067] Electrical coupling between each of the metal foils 120 and a respective one of the conductive pads 140 may be achieved as depicted in Figure 6B by positioning an insulating layer 130 between each of the metal foils 120 and the corresponding conductive pad 140. The insulating layer 130 in this Figure 6B embodiment has an opening behind each of the plurality of metal foils 120 through which a conductive path (e.g., metal, solder, etc.) is provided.

[0068] All variations of the embodiment of FIG. 6 also include a plurality of flexible polymer regions 30, each having a front surface and disposed on and in front of a respective one of the plurality of metal foils 120. Specifications for the polymer regions 30 in this embodiment are as follows: (1) at least one frequency between 100 kHz and 500 kHz, each of the polymer regions 30 has a dielectric constant of at least 20; and (2) each of the polymer regions 30 has a thickness of less than 20 μm in a direction perpendicular to its front surface. In some embodiments, the thickness of each of the polymer regions 30 multiplied by its dielectric strength is at least 50 V; in some embodiments, this value is at least 200 V. Any of the polymer materials detailed above in connection with the embodiment of FIG. 5 may be used to implement the polymer regions 30 in this embodiment of FIG. 6.

[0069] 6, the polymer regions 30 can be printed, sprayed, or cast directly onto the metal foil 120 of the metal foil, which makes it very easy to obtain very thin polymer layers. In some embodiments (e.g., embodiments in which the polymer regions 30 are printed, sprayed, or cast directly onto the metal foil 120 of the metal foil), the polymer regions have a thickness of less than 5 μm.

[0070] Increasing the total area covered by the metal foil 120 increases the capacitance of the entire device. In one embodiment, the area of ​​the multiple metal foils totals at least 25 cm 2 becomes.

[0071] The embodiment of Figure 6 may be secured to a person's skin using a flexible third layer 40, the nature of which is similar to the flexible third layer described above in connection with the embodiment of Figure 5. Additionally, a layer of conductive hydrogel 50 may be disposed on the front surface of each of the polymer regions, as described above in connection with the embodiment of Figure 5.

[0072] Multiple thermistors may also be incorporated into this FIG. 6 embodiment, as described above in connection with the FIG. 5 embodiment.

[0073] 7A and 7B illustrate an embodiment similar to the previously described embodiment of FIG. 6, except that it uses an alternative approach to making electrical connections between each of the metal foils 120 of the metal foil and a respective one of the conductive pads 140. As in the approach of FIG. 6, an insulating layer 130 is positioned between each of the metal foils 120 and the corresponding conductive pad 140. However, the insulating layer 130 in this FIG. 7 embodiment does not have openings behind each of the multiple metal foils 120. Instead, the insulating layer 130 in this FIG. 7 embodiment is continuous. Electrical connections between each of the metal foils 120 of the metal foil and the conductive pads 140 of the flex circuit are made using edge or edge electrical connections 160 between the conductive pads 140 and the metal foils 120 of the metal foil.

[0074] To use the transducer arrays depicted in any of Figures 5-7, a pair of transducer arrays is secured to a person's skin on either side of a target area on the person's body, and an AC voltage is applied between the two transducer arrays. Each conductive pad 20 (in the embodiment of Figure 5) or metal foil 120 (in the embodiments of Figures 6-7) acts as a plate of an individual capacitor, and each corresponding polymer region 30 acts as an insulating layer for that capacitor. An AC electric field is therefore capacitively coupled to the person's body through the capacitors.

[0075] If all of the capacitors have the same capacitance, the temperature of the corner / edge pads 20 (or foils 120 of the foils) is likely to overheat more frequently than the more centrally located pads / foils, for the same reasons as the prior art transducer array depicted in Figure 1. However, if the capacitance of the corner / edge pads 20 (or foils 120) in the embodiments of Figures 5-7 is reduced relative to the more centrally located pads / foils, the temperature among all pads 20 (or foils 120) of any given transducer array can be made uniform for the same reasons as the previously described embodiments of Figures 2-4.

[0076] 8 illustrates one approach to reducing the capacitance of the corner / edge pads 20 (or metal foils 120) in the embodiment of FIGS. 5-7 by using pads (or metal foils) that have smaller extent at the corners / edges of the transducer array (compared to the more centrally located portions of the transducer array). More specifically, if the more centrally located pads 20 (or metal foils 120) have an extent similar to upper region 310 and the more peripherally located pads 20 (or metal foils 120) have an extent similar to region 320 (smaller than region 310), region 330 (with circular void 335), or lower region 340 (with rectangular void 345), the extent of the more peripherally located pads 20 (or metal foils 120) will be smaller than the extent of the more centrally located pads 20 (or metal foils 120). Because the pads 20 (or metal foils 120) act as plates of a capacitor, the reduction in area results in a reduction in the capacitance of the more peripherally located pads 20 (or metal foils 120) relative to the more centrally located pads 20 (or metal foils 120). This reduces the current flowing through the more peripherally located pads 20 (or metal foils 120), which reduces the temperature at those pads 20 (or metal foils 120).

[0077] FIG. 9 illustrates an example of a suitable layout for the PCB pads in the embodiment of FIGS. 5-7 , customizing the printed circuit pad pattern to provide greater capacitance for more centrally located pads and less capacitance for more peripherally located pads. More specifically, in this example, the center pad 410 has 100% coverage to provide the maximum amount of capacitance, the top, bottom, right, and left pads 420 have smaller percentage coverage to provide smaller levels of capacitance, and the corner pads 430 have even smaller percentage coverage to provide even smaller levels of capacitance. Optionally, the distribution of the electric field for any given patient can be controlled by customizing the coverage pattern for each printed circuit pad and / or the layout and size of the printed circuit pads when the flex circuit is manufactured. Thus, currents can be balanced by using pads with varying coverage within a given array, which may be achieved using two, three, four, or more different coverage sizes.

[0078] FIG. 10 depicts an alternative approach for altering the pattern of coverage provided by any given pad on a flex circuit after the date and time of the flex circuit's original manufacture. In this approach, the flex circuit is first manufactured with multiple regions 500, each having multiple sub-regions 510 interconnected by severable conductive links 520 (depicted in detail i in FIG. 10 ), and an AC voltage is applied to only one of the sub-regions 510 by leads 530. Note that while there are nine regions 500 arranged in a 3×3 array 550 in the example depicted in FIG. 10 , the number of regions 500 may vary (e.g., between 9 and 30) as may the arrangement of the regions 500.

[0079] At some point after the initial fabrication of the flex circuit, a selected number of subregions 510 are disconnected by severing the conductive links 520 connecting to those subregions 510. For example, in detail ii, all of the links connecting to subregions 510 labeled G and N are disconnected. Also, in detail iii, all of the links connecting to subregions 510 labeled G, I, L, and N are disconnected. Disconnecting the links 520 can be accomplished using a variety of alternative techniques, such as, for example, destroying the links 520 with a laser or passing a sufficiently high current through the links 520 (similar to blowing a fuse). After disconnecting the links, the corresponding subregions 510 are effectively disconnected from the circuit, which reduces the active area and capacitance of the corresponding region 510.

[0080] This approach can be used to reduce the capacitance of corner-located regions of any given array (as described above) by cutting particular links 520 within corner-located regions 500 of the overall array 550. Advantageously, this approach can be used sometime after the initial fabrication of the flex circuit (e.g., to customize the capacitance of a portion of the overall array 550 to suit the needs of an individual patient).

[0081] Other techniques for reducing the capacitance of the corner / edge pads 20 (or metal foil 120) may also be used, including reducing the capacitance of the pads or metal foil by increasing the thickness or decreasing the dielectric constant of the corresponding polymer regions 30. In each case, this technique can be used to balance the currents by using pads with varying thicknesses of the polymer regions in a given array, or by using pads with varying dielectric constants of the polymer regions in a given array, which may be achieved using two, three, four or more different changes in the respective thicknesses or dielectric constants.

[0082] While the present invention has been disclosed with reference to particular embodiments, numerous improvements, modifications, and variations to the described embodiments are possible without departing from the sphere and scope of the invention as defined in the appended claims. Accordingly, it is intended that the present invention not be limited to the described embodiments, but rather have its full scope defined by the language of the following claims, and equivalents thereof. [Explanation of symbols]

[0083] 10 electrodes 20 Conductive Pad 25 Flex Circuit 30 Flexible polymer region 40 Flexible Third Layer 50 Conductive Hydrogel 60 Thermistor 120 Multiple Metal Foils 130 Insulating layer 140 Conductive Pad 145 Flex Circuit 160 Electrical Connection of Sides or Edges 200 transducer array 210 Ceramic elements, elements 212 Metallization Pattern, Metallization Layout 220 Ceramic elements, elements 222 Metallization Pattern, Metallization Layout 230 elements 232 Metallization Pattern, Metallization Layout 235 Circular Void 240 elements 242 Metallization Pattern, Metallization Layout 245 Rectangular Void 250 Base material 262 Main area 266 subarea 268 Conductive Link, Link 310 Upper Region, Region 320, 330, 340 area 335 Circular Void 345 Rectangular Void 410 Center Pad 420 Top, Bottom, Right, and Left Pads 430 Corner Pad 500 areas 510 subarea 520 Conductive link, link 530 lead wire 550 array A1, A3, A7, A9 Corner elements, elements Elements centered on A2, A4, A5, A6, A8, C Center of gravity

Claims

1. 1. An apparatus for applying an alternating electric field to a living subject, comprising: a plurality of conductive regions each having a front surface and a respective area; a plurality of regions of dielectric material each having (i) a respective front surface, and (ii) a respective rear surface disposed opposite the front surface of a respective one of the conductive regions; a substrate configured to hold the front surfaces of the plurality of regions of dielectric material on or within the subject's body and to support the plurality of conductive regions at respective locations distributed about a center of gravity of all of the plurality of conductive regions; at least one electrical conductor disposed in electrical contact with the plurality of conductive regions; the plurality of conductive regions includes at least one first conductive region and a plurality of second conductive regions, each of the second conductive regions positioned farther from the center of gravity than the at least one first conductive region, and the extent of each of the second conductive regions is at least 10% less than the extent of each of the at least one first conductive region.

2. 2. The apparatus of claim 1, wherein each of the regions of dielectric material comprises a ceramic disk, and each of the plurality of conductive regions comprises a layer of metal disposed on the rear surface of a respective one of the ceramic disks.

3. 10. The apparatus of claim 1, wherein each of the regions of dielectric material comprises a planar ceramic material, and each of the plurality of conductive regions comprises a layer of metal disposed on the rear surface of a respective one of the ceramic materials.

4. 10. The apparatus of claim 1, wherein each of the plurality of conductive areas comprises a pad of a printed circuit and each of the areas of dielectric material comprises a polymer film.

5. 10. The apparatus of claim 1, wherein each of said plurality of conductive regions comprises a pad of a printed circuit, and each of said regions of said dielectric material is implemented using a different area of ​​a single continuous polymer film.

6. 10. The device of claim 1, wherein each of the plurality of conductive regions comprises a layer of metal foil and each of the regions of dielectric material comprises a polymer film.

7. 10. The device of claim 1, wherein each of the plurality of conductive regions comprises a layer of metal foil, and each of the regions of the dielectric material is implemented using a different section of a single continuous polymer film.

8. 10. The device of claim 1, further comprising an adhesive layer configured to hold the substrate against a person's skin so that the front surfaces of the plurality of regions of dielectric material face the body of the subject.

9. 2. The device of claim 1, wherein the plurality of conductive regions further includes a plurality of third conductive regions, each of the third conductive regions positioned farther from the center of gravity than the plurality of second conductive regions, and wherein the extent of each of the third conductive regions is at least 10% less than the extent of each of the second conductive regions.

10. 1. An apparatus for applying an alternating electric field to a living subject, comprising: a plurality of conductive regions each having a front surface and a respective area; a plurality of regions of dielectric material each having (i) a respective front surface, and (ii) a respective rear surface disposed opposite the front surface of a respective one of the conductive regions; a substrate configured to hold the front surfaces of the plurality of regions of dielectric material on or within the subject's body and to support the plurality of conductive regions at respective locations distributed about a center of gravity of all of the plurality of conductive regions; a plurality of temperature sensors each disposed in thermal contact with a respective region of the dielectric material; at least one electrical conductor disposed in electrical contact with the plurality of conductive regions; the plurality of conductive regions includes at least one first conductive region and a plurality of second conductive regions, each of the second conductive regions positioned farther from the center of gravity than the at least one first conductive region, and a capacitance associated with each of the second conductive regions is at least 10% less than a capacitance associated with each of the at least one first conductive region.

11. 11. The apparatus of claim 10, wherein each of the second conductive regions has an extent that is at least 10% less than each of the at least one first conductive region.

12. 11. The apparatus of claim 10, wherein the region of the dielectric material disposed opposite the front surface of each of the second conductive regions is at least 10% thicker than the region of the dielectric material disposed opposite the front surface of each of the at least one first conductive region.

13. 11. The device of claim 10, wherein the region of the dielectric material disposed opposite the front surface of each of the second conductive regions has a dielectric constant that is at least 10% less than the region of the dielectric material disposed opposite the front surface of each of the at least one first conductive region.

14. 1. An apparatus for applying an alternating electric field to a living subject, comprising: a flex circuit comprising: (a) at least one first conductive pad positioned on a front side of the flex circuit, each pad having a first extent; (b) a plurality of second conductive pads positioned on the front side of the flex circuit at locations peripheral to the at least one first conductive pad, each pad having a respective extent at least 10% less than the first extent; and (c) at least one conductive trace positioned in electrical contact with the at least one first conductive pad and the plurality of second conductive pads, the at least one conductive trace being positioned such that each of the at least one first conductive pad and each of the second conductive pads can be driven by an electrical signal; at least one first flexible polymer region, each having a front surface, each disposed on and in front of a respective one of the at least one first conductive pads on the front side of the flex circuit; a plurality of second flexible polymer regions each having a front surface and each disposed on and in front of a respective one of the second conductive pads on the front side of the flex circuit; wherein at least one frequency between 100 kHz and 500 kHz, each of the polymer regions has a dielectric constant of at least 20; A device wherein each of the polymer regions has a thickness in a direction perpendicular to its front surface that is less than 20 μm.

15. a plurality of thermistors positioned on a rear side of the flex circuit, each of the plurality of thermistors being disposed in thermal contact with a respective one of the plurality of second conductive pads; 15. The apparatus of claim 14, wherein the flex circuit further includes a plurality of conductive traces providing access to the plurality of thermistors.

16. a flexible third layer configured to support the flex circuit, the flexible third layer having a front surface, wherein (a) a first portion of the front surface of the flexible third layer is coated with an adhesive that adheres to and is easily removable from a person's skin, and (b) the first portion is positioned outwardly relative to the flex circuit such that when the first portion is pressed against an area of ​​skin, the adhesive in the first portion adheres to the skin and holds the plurality of second flexible polymer regions adjacent to the skin; a layer of conductive hydrogel disposed on the front surface of each of the first flexible polymer regions and on the front surface of each of the second flexible polymer regions, the hydrogel positioned to contact the skin when each of the second flexible polymer regions is held adjacent the skin by the adhesive; The apparatus of claim 14 further comprising:

17. 15. The device of claim 14, wherein each of the polymer regions has a thickness of less than 5 μm.

18. 15. The apparatus of claim 14, wherein each of the second conductive pads comprises a plurality of conductive sub-regions interconnected by severable conductive links.

19. a flexible third layer configured to support the flex circuit, the flexible third layer having a front surface, wherein (a) a first portion of the front surface of the flexible third layer is coated with an adhesive that adheres to and is easily removable from a person's skin, and (b) the first portion is positioned outwardly relative to the flex circuit such that when the first portion is pressed against an area of ​​skin, the adhesive in the first portion adheres to the skin and holds the plurality of second flexible polymer regions adjacent to the skin; a layer of conductive hydrogel disposed on the front surface of each of the first flexible polymer regions and each of the second flexible polymer regions, the hydrogel positioned to contact the skin when each of the second flexible polymer regions is held adjacent the skin by the adhesive; and a plurality of thermistors positioned on the rear side of the flex circuit, each thermistor being disposed in thermal contact with a respective one of the plurality of second conductive pads; 15. The apparatus of claim 14, wherein the flex circuit further includes a plurality of conductive traces providing access to the plurality of thermistors.

20. 20. The device of claim 19, wherein each of the polymer regions has a thickness of less than 5 μm.

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