Array for delivering tumor treating fields (tt fields) with individually accessible electrode elements and temperature sensors

Abstract

A tumor treating field (TT field) can be delivered to a subject's body at a higher field intensity by shutting down one or more electrode elements in the transducer array that are overheating. This can be accomplished by using a thermal resistor that senses the temperature of each electrode element. The partial wiring of each transducer array is shared between the electrode element and the thermal resistor by using a plurality of conductors, each of which is electrically connected (a) a pin of a connector, (b) a respective electrode element, and (c) a respective thermal resistor. In some embodiments, all thermal resistors are wired in series. In other embodiments, all thermal resistors share a common connection.

Description

[0001] Cross-references to related applications

[0002] This application claims the benefit of U.S. Provisional Application 62 / 955,664, filed December 31, 2019, the entirety of which is incorporated herein by reference. Background Technology

[0003] TT Fields therapy is a proven approach for treating cancer. Figure 1 It is the existing technology Epton used for transmitting TT fields. A schematic representation of the system. The TT field is delivered to the patient via four transducer arrays 21 to 24, which are placed on the patient's skin, close to the tumor (e.g., as shown). Figures 2A-2D (As described in the treatment for a person with malignant glioma). Converter arrays 21 to 24 are arranged in two pairs, and each converter array is connected to an AC signal generator 20 via a multi-wire cable. The AC signal generator operates as follows: (a) during a first time period, it sends an AC current through one pair of arrays 21, 22, which induces an electric field with a first direction through the tumor; then (b) during a second time period, it sends an AC current through another pair of arrays 23, 24, which induces an electric field with a second direction through the tumor; then steps (a) and (b) are repeated for the duration of treatment.

[0004] Each converter array 21 to 24 is configured as a set of capacitively coupled electrode elements E (e.g., a set of nine electrode elements, each approximately 2 cm in diameter) interconnected via flexible circuitry. Each electrode element includes a conductive substrate on which a dielectric layer (more specifically, a ceramic material layer with a high dielectric constant) is disposed. Each electrode element is sandwiched between a conductive medical gel layer and adhesive tape. When the array is placed on a patient, the medical gel conforms to the contours of the patient's skin and ensures good electrical contact between the device and the body. As the patient performs their daily activities, the adhesive tape holds the entire array in place on the patient.

[0005] The amplitude of the alternating current transmitted via the converter array is controlled such that the skin temperature (as measured on the skin beneath the converter array) does not exceed a safe threshold of 41°C. The temperature of the patient's skin is measured using a thermal resistor T placed beneath some disks of the converter array. In existing... In the system, each array includes eight thermal resistors, one of which is placed below a corresponding disk in the array. (Note that most arrays include more than eight disks; in this case, temperature measurements are performed only below a subset of the disks within the array.)

[0006] The AC signal generator 20 obtains temperature measurements from all 32 thermistors (4 arrays x 8 thermistors per array), and a controller in the AC signal generator uses the temperature measurements to control the current to be delivered via each pair of arrays in order to maintain the temperature on the patient’s skin below 41 °C. The current itself is delivered to each array via an additional wire from the AC signal generator 20 to each array (i.e., one wire 28 for each of arrays 21-24). And the additional wire (not shown) for each of arrays 21-24 serves as a common return for all 8 thermistors. Thus, in the existing Iridium system, each of the four cables terminating in arrays 21-24 has a total of 10 conductors. SUMMARY

[0007] One aspect of the present disclosure is directed to a first device for applying an alternating electric field to a body of a subject. The first device includes a plurality of electrode elements, a support configured to hold the electrode elements against the body of the subject, and a plurality of thermistors. Each of the thermistors has a first terminal and a second terminal, and each of the thermistors is positioned to sense a temperature at a corresponding respective one of the electrode elements. The first device further includes a connector having a plurality of first pins and a second pin, a plurality of first conductors each providing an electrically conductive path between (a) a respective one of the first pins, (b) a respective one of the electrode elements, and (c) the first terminal of a corresponding thermistor, and a second conductor providing an electrically conductive path between the second pin of the connector and the second terminal of at least one of the thermistors.

[0008] In some embodiments of the first device, the second terminals of all of the thermistors are wired together. Optionally, in these embodiments, the second terminals of all of the thermistors can be wired together using at least one of (a) at least one trace on a flexible circuit and (b) at least one wire.

[0009] In some embodiments of the first device, the plurality of thermistors are arranged in series, beginning with a first one of the thermistors and ending with a last one of the thermistors, and the second terminal of each of the thermistors other than the last one is wired to the first terminal of a respective next thermistor, and the second conductor provides an electrically conductive path between the second pin of the connector and the second terminal of the last thermistor.

[0010] In some embodiments of the first device, the second conductor provides an electrically conductive path between the second pin and the second terminal of only one of the thermistors.

[0011] In some embodiments of the first device, the plurality of electrode elements includes at least four electrode elements, and the plurality of thermistors includes at least four thermistors.

[0012] In some embodiments of the first apparatus, the plurality of electrode elements includes at least nine electrode elements, and the plurality of thermal resistors includes at least nine thermal resistors.

[0013] In some embodiments of the first apparatus, each of the electrode elements includes an electrically conductive plate and a dielectric layer disposed on the electrically conductive plate, and the support is configured to hold the electrode elements against the subject’s body such that the dielectric layer of each of the electrode elements faces the subject’s body.

[0014] In some embodiments of the first apparatus, the second terminals of all of the thermal resistors are wired together, and the second conductor provides an electrically conductive path between the second pin and the second terminals of all of the thermal resistors.

[0015] Another aspect of the present application is directed to a second apparatus for applying an alternating electric field to a subject’s body using a plurality of electrode elements. Each of the plurality of electrode elements is disposed in thermal contact with a respective thermal resistor. The second apparatus includes an AC signal generator that generates an AC output signal, and a connector that includes a plurality of pins. Each of the pins corresponds to a respective one of the plurality of electrode elements. The second apparatus further includes a first plurality of switches. Each of the first plurality of switches is configured to selectively apply or not apply the AC output signal to a respective one of the pins. The second apparatus further includes an amplifier configured to receive an electrical signal from each of the thermal resistors and generate a corresponding output. The electrical signals from the thermal resistors arrive via the same pins corresponding to the plurality of electrode elements. The second apparatus further includes a controller configured to control the first plurality of switches based on the outputs of the amplifier in order to individually adjust a duty cycle of the AC signal applied to each of the plurality of pins.

[0016] In some embodiments of the second apparatus, the controller is configured to (a) determine when at least one of the electrode elements is hotter than the other electrode elements based on the outputs of the amplifier, and (b) control the first plurality of switches in order to reduce the duty cycle of the AC signal applied to the at least one respective pin. In some embodiments of the second apparatus, the controller is configured to (a) determine when at least one of the electrode elements is hotter than a threshold level based on the outputs of the amplifier, and (b) control the first plurality of switches in order to reduce the duty cycle of the AC signal applied to the at least one respective pin.

[0017] In some embodiments of the second apparatus, the plurality of electrode elements includes at least four electrode elements, the plurality of pins includes at least four pins, and the first plurality of switches includes at least four switches. In some embodiments of the second apparatus, the plurality of electrode elements includes at least nine electrode elements, the plurality of pins includes at least nine pins, and the first plurality of switches includes at least nine switches.

[0018] Some embodiments of the second device also include a second plurality of switches, each of which is arranged to route a signal from a respective one of the plurality of pins to the first input of the amplifier. In these embodiments, the controller is also configured to control the second plurality of switches to sequentially select each of the plurality of pins and sequentially obtain a temperature reading from each of the thermal resistors. Optionally, in these embodiments, the connector includes an additional pin, and the device also includes an additional switch arranged to route a signal from the additional pin to the second input of the amplifier.

[0019] Some embodiments of the second device also include a second plurality of switches, each of which is arranged to route a signal from a respective one of the plurality of pins to the first input of the amplifier. In these embodiments, the controller is also configured to control the second plurality of switches to sequentially select each of the plurality of pins and sequentially obtain a temperature reading from each of the thermal resistors. The connector includes an additional pin, and the device also includes: (a) an additional switch arranged to route a signal from the additional pin to the second input of the amplifier; and (b) a third plurality of switches, each of which is arranged to route a signal from a respective one of the plurality of pins to the additional pin. In these embodiments, the controller is also configured such that when a given switch of the first plurality of switches is open, the controller closes a corresponding respective switch of the third plurality of switches.

[0020] Some embodiments of the second device also include a second plurality of switches, each of which is arranged to route a signal from a respective one of the plurality of pins to the first input of the amplifier. In these embodiments, the controller is also configured to control the second plurality of switches to sequentially select each of the plurality of pins and sequentially obtain a temperature reading from each of the thermal resistors. The connector includes an additional pin, and the device also includes: (a) an additional switch arranged to route a signal from the additional pin to the second input of the amplifier; and (b) a third plurality of switches, each of which is arranged to route a signal from a respective one of the plurality of pins to the additional pin. In these embodiments, the controller is also configured such that when a given switch of the first plurality of switches is open, the controller closes a corresponding respective switch of the third plurality of switches.

[0021] Another aspect of the present invention relates to a first method of applying an alternating electric field to a body of a subject using a plurality of electrode elements. Each of the plurality of electrode elements is disposed in thermal contact with a respective thermal resistor. The first method includes: applying an AC signal to each of the electrode elements with a respective duty cycle such that an alternating electric field is induced within the subject; inputting a signal from each of the thermal resistors; determining a temperature of each of the electrode elements based on the inputted signal; and adjusting the duty cycle of the AC signal applied to the electrode elements based on the determined temperature. After the adjustment, the duty cycle of the AC signal applied to at least one of the electrode elements is different than the duty cycle of the AC signal applied to another of the electrode elements.

[0022] In some embodiments of the first method, the adjustment includes reducing the duty cycle of the AC signal applied to at least one electrode element that is hotter than at least one other electrode element. In some embodiments of the first method, the adjustment includes reducing the duty cycle of the AC signal applied to any of the hottest electrode elements. In some embodiments of the first method, the adjustment includes reducing the duty cycle of the AC signal applied to any electrode element whose temperature exceeds a threshold level.

[0023] In some embodiments of the first method, the adjustment includes reducing the duty cycle of the AC signal applied to any electrode element whose rate of heating exceeds a threshold level. In some embodiments of the first method, the adjustment includes turning off the AC signal applied to any electrode element whose temperature exceeds a first threshold level and turning on the AC signal applied to at least one electrode element whose temperature is below a second threshold level, wherein the second threshold level is lower than the first threshold level. Attached Figure Description

[0024] Figure 1 It is an existing technology for transmitting TT fields. A schematic representation of the system.

[0025] Figures 2A-2D It describes positioning a converter array in a person's head for the treatment of brain tumors.

[0026] Figure 3 A first embodiment of a converter array that provides a separate conductor for each individual electrode element is described.

[0027] Figure 4 Is using Figure 3 A block diagram of a system that uses four copies of a converter array to apply a TT field to a subject.

[0028] Figure 5 A second embodiment of a converter array is described, which provides a separate conductor for each individual electrode element.

[0029] Figure 6 Is using Figure 5 A block diagram of a system that uses four copies of a converter array to apply a TT field to a subject.

[0030] Figure 7 It is suitable for implementation Figure 4 and Figure 6 A schematic diagram of the circuit for each of the switches in groups 1L and 1R in the embodiment.

[0031] Various embodiments are described in detail below with reference to the accompanying drawings, wherein the same reference numerals denote the same elements. Detailed Implementation

[0032] While the above-described Figure 1 method is very effective at delivering TT fields to a tumor, the effectiveness of the treatment will be reduced if each of the elements in the four transducer arrays 21-24 fails to maintain good electrical contact with the individual's body. For example, this can occur if the hydrogel under one or more elements of a transducer array dries out over time or due to hair growth under one or more of the elements.

[0033] Assume, for example, that there are 9 electrode elements E in each of the transducer arrays 21-24, that the hydrogel under a single electrode element E on the front transducer array 21 has dried out; and that sufficient hydrogel exists under (a) all other electrode elements E of that transducer array 21 and (b) all electrode elements E of the other transducer arrays 22-24. In this case, the electrical resistance between the single electrode element E and the individual's body will be higher than the electrical resistance between any of the other electrode elements and the individual's body. And this increased resistance will cause the temperature of the single electrode element E to rise more than the other electrode elements.

[0034] In this case, because all of the electrode elements E in each of the transducer arrays 21-24 are wired in parallel, the AC signal generator 20 must limit the current applied to the entire front / back pair of transducer arrays 21, 22 in order to keep the temperature of the single electrode element E on the front array 21 below 41°, even though the temperature at all of the remaining electrode elements E on the front and back transducer arrays 21, 22 can be well below 41°. And this reduction in current will cause the strength of the electric field at the tumor to correspondingly decrease, which can reduce the efficacy of the treatment.

[0035] The embodiments described herein advantageously provide the ability to control the current routed through individual electrode elements without unduly increasing the number of conductors in the cable terminating at the transducer array, and without relying on active components positioned on or near the transducer array.

[0036] Unlike prior art configurations in which all of the electrode elements E in each of the transducer arrays 21-24 are wired in parallel, the embodiments described herein have a separate conductor for each of the multiple electrode elements in each of the transducer arrays. This configuration enables the current to be turned on and off independently for any given individual electrode element of any of the electrode elements in the array.

[0037] One possible method for controlling the current on an element-by-element basis is to Figure 1In contrast to the prior art configurations depicted, the electrode elements are rewired so that they are not connected in parallel, but rather individual wires go to each individual electrode element. However, a problem with this approach is that it requires almost twice the number of conductors in each cable to the transducer array. For example, in a transducer array with 9 electrode elements, a total of 19 wires would be required in each cable (i.e., 9 for providing individual access to each of the 9 electrode elements, an additional 9 for the signals from the thermistors, plus one additional wire to act as a common return for all 9 thermistors). And this significant increase in the number of wires in each cable tends to decrease cable flexibility and increase bulk, which can make the system more difficult to use and decrease patient compliance.

[0038] One way to reduce the total number of wires in each cable is to locate active components (e.g., electronic control switches) on or near the transducer array. For example, a set of switches can be used to control which of the electrode elements is turned on at any given moment (e.g., as described in US 16 / 686,918, filed November 18, 2019, which is hereby incorporated by reference in its entirety). Alternatively or additionally, an analog multiplexer can be used to multiplex the temperature readings obtained from the thermistors into a cable with a small number of conductors (e.g., as described in US 2018 / 0050200, which is hereby incorporated by reference in its entirety). But locating active components on or near the transducer array introduces its own set of drawbacks (e.g., increased weight and complexity, plus potential problems with sterilization).

[0039] Figure 3 A first embodiment of a transducer array 50 is depicted that provides a separate conductor for each individual electrode element 51 without causing a significant increase in the number of wires in each cable to a given transducer array, nor requiring active components to be located on or near the transducer array. As will be described below in connection with Figure 4 Four copies of the transducer array 50 are preferably used to apply TT field therapy to a person’s head (or other body part).

[0040] Each transducer array 50 includes a plurality of electrode elements 52, which are Figure 3 Embodiments are labeled El through E9 for ease of reference. Each of these electrode elements 52 has a conductive substrate (e.g., a circular metal substrate) with a dielectric layer disposed thereon. In some preferred embodiments, each of these electrode elements 52 is similar to The prior art electrode elements used in the system are disk-shaped capacitive-coupled electrode elements (e.g., with a diameter of 2 cm), and the dielectric layer includes a thin layer of ceramic material with a high dielectric constant. However, unlike Systems and methods Figure 1 (where all elements are wired in parallel), individual conductors from each of the electrode elements 52 to the connector 57. These conductors are numbered 1 through 9, just above the "wire routing" block 55, which brings the individual conductors together into a single cable 56. In some preferred embodiments, the electrical connection to each of the electrode elements 52 includes one or more traces on a flexible circuit and / or one or more conductive wires. Figure 3

[0041] In the embodiment depicted in FIG. 1, the electrode elements 52 are capacitive-coupled electrode elements. In other embodiments, the electrode elements 52 can be galvanic-coupled electrode elements. In still other embodiments, the electrode elements 52 can be a combination of capacitive-coupled and galvanic-coupled electrode elements. Figure 3 In the embodiment depicted in FIG. 1, all of the capacitive-coupled electrode elements 52 are held in place by a support structure 59. The support structure is configured to hold the electrode elements against the body of the subject, such that the dielectric layer of the electrode elements 52 faces the body of the subject and can be positioned in contact with the body of the subject. Optionally, the support structure can include a flexible backing 59, such as a layer of sponge rubber material. Preferably, a hydrogel layer is disposed between the dielectric layer of the electrode elements 52 and the body of the subject when the transducer array 50 is placed against the body of the subject. The construction of the support structure 59 can be implemented using any of a variety of well-known methods for electrode elements that will be apparent to those skilled in the art, including but not limited to self-adhesive fabric, sponge rubber, or plastic sheeting.

[0042] Each transducer array 50 also includes a plurality of thermistors 54, with one thermistor positioned at each of the electrode elements 52, such that the thermistors 54 can sense the temperature of the corresponding electrode elements 52. This can be accomplished, for example, by incorporating a hole or recess in the center of each electrode element 52, and positioning a corresponding one of the thermistors 54 in the hole or recess. Each of the thermistors 54 has a first terminal (i.e., the lower terminal of the thermistor in FIG. 1) and a second terminal (i.e., the upper terminal of the thermistor in FIG. 1). Figure 3 Figure 3

[0043] Each transducer array 50 also has a connector 57 for sending electrical signals to and from the transducer array 50. The connector 57 has a plurality of first pins, and a second pin. In the illustrated embodiment, the number of first pins is the same as the number of electrode elements 52, and each of the first pins corresponds to a corresponding one of those electrode elements 52. And in the illustrated embodiment, there is only a single second pin, labeled C. It should be noted that, as used herein, the term "pin" can refer to either a male or female pin of the connector 57.

[0044] Each transducer array 50 also has a plurality of first conductors, and the number of these first conductors will depend on the number of electrode elements 52. In the embodiment depicted in FIG. 1, which contains nine electrode elements 52, there are nine first conductors. These first conductors are numbered 1 through 9, just above the "wire routing" block 55, which brings the individual conductors together into a single cable 56. In some preferred embodiments, the electrical connection to each of the electrode elements 52 includes one or more traces on a flexible circuit and / or one or more conductive wires. Figure 3 ​​​In the embodiment depicted in FIG. 1, the first conductors are implemented using a plurality of electrical wire segments and a plurality of traces on a flexible circuit. In the embodiment depicted in FIG. 1, the second conductors are implemented using a plurality of electrical wire segments and a plurality of traces on a flexible circuit.

[0045] Each transducer array 50 also has second conductors that provide an electrically conductive path between a second pin of the connector 57 and a second terminal (i.e., an upper terminal in Figure 3 FIG. 1) of at least one of the thermal resistors 54. In the embodiment depicted in FIG. 1, the second conductors are implemented using a plurality of electrical wire segments and a plurality of traces on a flexible circuit. Figure 3 In the embodiment depicted in FIG. 1, the second terminals of all of the thermal resistors are wired together. In this embodiment, the second conductors provide an electrically conductive path between a second pin of the connector 57 and the second terminals of all of the thermal resistors 54. The second conductors can optionally be implemented using a plurality of electrical wire segments and / or a plurality of traces on a flexible circuit.

[0046] Because the connector 57 has a separate first pin corresponding to each of the individual electrode elements 52, and because an electrically conductive path exists between each of the first pins and a respective one of the electrode elements 52, a system that mates with the connector 57 can selectively energize or not energize each of the electrode elements 52 by applying or not applying a signal to the respective first pin on the connector 57.

[0047] Also, because the connector 57 has a separate first pin corresponding to the first terminal of each of the thermal resistors 54, and because an electrically conductive path exists between each of the first pins and a respective one of the thermal resistors 54, a system that mates with the connector 57 has access to the first terminal of each of the thermal resistors 54. In addition, because the second terminals of all of the thermal resistors 54 are wired together and connected to a second pin (labeled C), a system that mates with the connector 57 also has access to the second terminal of each of the thermal resistors 54. Thus, a system that mates with the connector 57 can measure the resistance of any of the electrode elements in the thermal resistors 54. This can be accomplished, for example, by routing a known current through each thermal resistor 54 and measuring the voltage that appears across each thermal resistor.

[0048] Notably, because any given first pin on the connector 57 corresponds to a respective one of the individual electrode elements 52 and also corresponds to a respective one of the individual thermal resistors 54, each of the first pins on the connector 57 provides two functions. This reduces the number of electrical wires that must be included in each of the cables 56, which in turn advantageously increases cable flexibility and decreases complexity.

[0049] Figure 4 is a block diagram of a system that uses four copies of the transducer array 50 (described above in connection with Figure 3 Figure 4 In the present case, the four copies are labeled 50A, 50P, 50L, and 50R, where A, P, L, and R stand for anterior, posterior, left, and right, respectively. Figure 4 The lower portion of FIG. 1 depicts the AC voltage generator 35 and the "CAD box" 30 as separate blocks, with the latter including the temperature measurement block 32, the controller 34, and the switch sets 1L, 2L, 3L, 1R, 2R, and 3R. In some embodiments, the elements in those two blocks 35, 30 can be physically divided into two separate housings. But in alternative embodiments, the elements in those two blocks 35, 30 are combined into a single housing.

[0050] For purposes of clarity, Figure 4 In the present case, only the left and right channels are depicted. But the remaining channels (i.e., the anterior and posterior channels) operate in the same manner as the left and right channels, respectively. In addition, for purposes of clarity, Figure 4 In the present case, each of the transducer arrays 50 in FIG. 1 is depicted as having only 4 electrode elements 52 and four thermal resistors 54. But it is contemplated that the actual system will have a larger number (e.g., between 9 and 30) of electrode elements and thermal resistors, depending on the number of electrode elements 52 actually used in each of the transducer arrays 50, and will also have a larger number of certain other elements (e.g., switches, conductors, etc.).

[0051] Figure 4 ​The system can measure the temperature of the thermal resistors 54 in the left side channel 50L by sequentially selecting each of the thermal resistors through the electronically controlled switches in group 2L, which can be implemented using bi-directional analog switches. For example, switch C and switch 1 should be closed to select thermal resistor Tl; switch C and switch 2 should be closed to select thermal resistor T2; and so on. After any given one of the thermal resistors Tl to T4 within the transducer array 50L has been selected, the temperature measurement block (TMB) 32 can determine the temperature of the thermal resistor by measuring the resistance of the thermal resistor. This can be accomplished, for example, by using a current source that generates a known current (e.g., 150 μΑ) that is routed into whichever thermal resistor is selected at any given moment by the switch group 2L. The known current will cause a voltage to appear across the selected thermal resistor (Tl to T4), and the temperature of the selected thermal resistor can be determined by measuring that voltage. The controller 34 executes a program that sequentially selects each of the thermal resistors Tl to T4 and sequentially measures the voltage that appears across each of the thermal resistors (which is indicative of the temperature at the selected thermal resistor). An example of suitable hardware and a program that can be used to obtain temperature readings from each of the thermal resistors is described in US 2018 / 0050200, which is hereby incorporated by reference in its entirety.

[0052] Measuring the temperature of the thermal resistors 54 in the right side channel 50R is accomplished using the same method described above in connection with the left side channel 50L, except that the switch group 2R is used instead of group 2L. Corresponding switch groups (not shown) are also provided for the other channels 50A, 50P, and a similar method is used in those channels as well.

[0053] Based on the temperature readings obtained from the thermal resistors 54 (Tl to T4), the controller 34 controls the switches in group IL to turn on or off the current to each of the corresponding electrode elements 52 (El to E4) that originates from the AC voltage generator 35. For example, to have the current to all four electrode elements 52 in the on state, all four switches in group IL should be closed. To interrupt the current to electrode element El, switch 1 in group IL should be opened; and to interrupt the current to electrode element E2, switch 2 in group IL should be opened; and so on.

[0054] Controlling the current that is routed through individual electrode elements can be used to reduce or eliminate a reduction in the average current that is coupled into a person's body when a small number of electrode elements start to overheat. This in turn can advantageously reduce or eliminate a reduction in the strength of the electric field at the tumor. This can be accomplished by programming the controller 34 to alternately turn on or off the current for each individual electrode element that starts to approach 41° in order to reduce the average current for those electrode elements without affecting the current through the remaining electrode elements (that do not approach 41°).

[0055] For example, assume the following situation: 500mA of current is passing through a transducer array comprising 10 electrode elements and only one of those electrode elements starts approaching 41°. Also assume that a 10% reduction in the current passing through the single electrode element would be necessary to keep the temperature at that single electrode element below 41°. Instead of achieving this 10% reduction in current by cutting the current passing through the entire transducer array from 500mA to 450mA (as in the prior art), the controller 34 can reduce the average current passing through the single electrode element by 10% by controlling the switches in group IL to turn the current passing through the single electrode element on and off at a 90% duty cycle while keeping all the remaining electrode elements current on all the time. Note that the switching rate must be fast enough, given the thermal inertia of the electrode elements, so that the instantaneous temperature at the single electrode element never exceeds 41°. For example, a 90% duty cycle can be achieved by turning the current on for 90 milliseconds and off for 10 milliseconds.

[0056] When using this method, the current passing through the remaining 9 electrode elements can remain unchanged (i.e., 50mA per electrode element), and only the current passing through the single electrode element is reduced to an average of 45mA. Subsequently, the average net total current passing through the transducer array will be 495mA (i.e., 9x50 + 45), which means that significantly more current is available to be coupled to the personal body without exceeding 41° at any of the electrode elements.

[0057] The controller 34 can even be configured to increase the current passing through the remaining nine electrode elements in order to compensate for the reduction in current passing through the single electrode element. For example, the current passing through the remaining nine electrode elements can be increased to 50.5mA per electrode element (e.g., by the controller 34 sending a request to the AC voltage generator 35 to increase the voltage by 1%). If this solution is implemented, the average net total current passing through the entire transducer array will be (9 electrodes x 50.5mA + 1 electrode x 50.5mA x 0.9 duty cycle) = 499.95mA, which is very close to the original 500mA current.

[0058] If at some later time (or even at the same time), the temperature at a second electrode element starts approaching 41°, similar techniques (i.e., reducing the duty cycle from 100% to somewhere less than 100%) can be used to prevent the temperature at the second electrode element from exceeding 41°.

[0059] In some embodiments, the technology can be used to individually customize the duty cycle at each of the electrode elements in order to maximize the current flowing through each of those electrode elements while keeping the temperature at each of those elements below 41°. Optionally, instead of taking remedial action to reduce the duty cycle only when the temperature at a given electrode element starts to approach 41°, the controller 34 can be configured to individually proactively set the duty cycle at each of the electrode elements in a given transducer array in order to equalize the temperature across all of the electrode elements in the array. For example, the controller 34 can be configured to individually set the duty cycle at each electrode element in order to maintain a temperature of about 40.5° at each of the electrode elements. Optionally, the controller 34 can be configured to send a request to the AC voltage generator 35 to increase or decrease the voltage as needed in order to achieve this result.

[0060] This approach can be used to ensure that each electrode element will carry the maximum average current possible (without exceeding 41°), which will provide increased field strength in the tumor and corresponding improvements in treatment.

[0061] In some embodiments, the controller 34 can be programmed to keep the temperature at all of the electrode elements below a safety threshold (e.g., below 41°C) by starting with all of the switches 1-4 in bank 1L closed so that the current is continuously on (i.e., at 100% duty cycle). Then, based on the signals arriving via the TMB 32, the controller 34 determines whether the temperature at each of the electrode elements exceeds an upper threshold (e.g., 40°C) that is below the safety threshold. When the controller 34 detects this condition, the controller 34 reduces the duty cycle of the corresponding switch in bank 1L by switching the corresponding digital output at the desired duty cycle. This interrupts the current to the corresponding electrode element 52 at the same duty cycle, thereby reducing the average current at the particular electrode element 52 where the temperature exceeds the upper threshold. The level of current reduction is determined by the duty cycle. For example, using a 50% duty cycle will cut the current in half; and using a 75% duty cycle will cut the current by 25%.

[0062] Notably, this procedure interrupts the current to only a particular one of the electrode elements 52 on the transducer array 50, without interrupting the current to the remaining electrode elements 52 on that transducer array 50. This provides a very significant advantage over the prior art because it eliminates or reduces the need to cut the current that will be routed through the electrode elements when only a few of those electrode elements are heating up.

[0063] A numerical example will be useful to illustrate this point. Assume that in a given transducer array 50, the current is 100 mA, and that the temperature at each of the electrode elements 52 is 40.5°. Assume further that the temperature at one of the electrode elements 52 starts to approach 41°. The controller 34 can be configured to reduce the duty cycle to that electrode element 52 by 50% (i.e., to 50% duty cycle) in order to reduce the average current at that electrode element 52 to 50 mA. This will reduce the temperature at that electrode element 52 to 40.5°, which is below the safety threshold of 41°. The remaining electrode elements 52 will continue to carry 100 mA of current, and their temperatures will remain at 40.5°. Figure 4In an embodiment, the left transducer array 50L and the right transducer array 50R are positioned on the left and right sides of the subject's head, respectively; all switches in groups 1L and 1R have a 100% duty cycle in the on state; and the AC voltage generator 35 initially outputs a current of 500 mA. An AC voltage will appear between the electrode elements 52 of the left transducer array 50L and the electrode elements 52 of the right transducer array 50R, and an AC current of 500 mA will be capacitively coupled through the electrode elements 52 through the subject's head. The controller 34 monitors the temperature at each of the electrode elements 52 in each of the transducer arrays 50L, 50R by inputting a signal from each of the temperature sensors 54 via the temperature measurement block 32. Assume now that the temperature at a given one of the electrode elements 52 in the left transducer array 50L has risen to 40°C. This condition will be reported to the controller 34 via the signal from the corresponding temperature sensor 54. When the controller 34 recognizes that the temperature of the given electrode element 52 has risen to 40°C, the controller 34 will switch the control signal to the corresponding switch in group 1L at the desired duty cycle so as to periodically interrupt the current to the given electrode element 52 and maintain a lower average current.

[0064] This is in sharp contrast to prior art devices in which, once the temperature at even a single one of the electrode elements 52 approaches 41°C, the prior art device must reduce the current flowing through all of the electrode elements.

[0065] Note that if the duty cycle is reduced at only one of the remaining electrode elements 52, it can be possible to maintain the original 500 mA current (and enjoy the benefits that result from using full current). However, if the duty cycle is reduced at a sufficiently large number of electrode elements 52, the original 500 mA current can have to be dropped. To achieve this, the controller 34 can send an instruction to the AC voltage generator 35. When the AC voltage generator 35 receives this request, the AC voltage generator 35 will reduce its output voltage, which will result in a drop in current.

[0066] Alternatively, the duty cycle selected by the controller 34 can be controlled based on the rate at which a given electrode element 52 heats up after current is applied to it (as measured via the temperature sensors 54 and the TMB 32). More specifically, if the controller 34 recognizes that a given electrode element 52 is heating up twice as fast as expected, the controller 34 can select a duty cycle of 50% for that electrode element. Similarly, if the controller 34 recognizes that a given electrode element 52 is heating up 10% faster than expected, the controller 34 can select a duty cycle of 90% for that electrode element.

[0067] In other embodiments, instead of curtailing the average current exactly by reducing the duty cycle, as described above by using the switches in group 1L to turn off the current to a given electrode element 52 and waiting until the temperature measured using the temperature sensor 54 falls below a second temperature threshold (e.g., below 38°C), the controller 34 can reduce the average current at the given electrode element 52 based on real-time temperature measurements. Once the temperature falls below this second temperature threshold, the controller 34 can resume the current to the given electrode element 52. This can be achieved, for example, by controlling the state of the previously turned-off switches in group 1L so that it resumes to an on state that will allow current to flow between the electrical conductor and the corresponding electrode element 52. In these embodiments, the current to the given electrode element 52 can be repeatedly turned off and on based on real-time temperature measurements in order to keep the temperature at the given electrode element 52 below the safety threshold.

[0068] Switching the current to each of the electrode elements 52 in the right channel 50R individually is achieved using the same method described above in connection with the left channel 50L, except that group 1R of switches is used instead of group 1L. Corresponding switch groups (not shown) are also provided for the other channels 50A, 50P, and similar methods are used in those channels as well.

[0069] It should be noted that the examples described above, which refer to duty cycles of 100%, 90%, 75%, 50%, etc., refer to the duty cycle of a given channel (e.g., left / right channel) being active within those time windows. In some preferred embodiments, the AC signal generator 35 operates as follows: (a) sends AC current through the front / back array 50A / 50P during a first time period (e.g., 1 second), which induces an electric field with a first direction through the tumor in the subject’s body; then (b) sends AC current through the left / right array 50L / 50R during a second time period (e.g., 1 second), which induces an electric field with a second direction through the tumor; then repeats steps (a) and (b) for the duration of the treatment. In these embodiments, the total duty cycle for any given channel (i.e., A / P channel or L / R channel) will be half the values in the examples described above. This is because operating at 100% duty cycle during a 1-second time window, then remaining off during the next 1-second time window, results in a total duty cycle of 50%. Similarly, operating at 90% duty cycle during a 1-second time window, then remaining off during the next 1-second time window, results in a total duty cycle of 45%.

[0070] Optionally, an additional group of switches 3L can be provided. Each of the switches in this group is wired in parallel with a corresponding one of the thermal resistors T1-T4, such that when a given one of the switches 1-4 is closed, the corresponding one of the thermal resistors T1-T4 will be shorted.

[0071] The reason for including the additional switch set 3L is that when (a) current from the AC voltage generator 35 flows through the electrode elements 52 of the left channel 50L, the subject's body, and the electrode elements 52 of the right channel 50, and (b) power to any of the electrode elements 52 of the left channel 50L is turned off by a corresponding one of the switches in set 1L, current can sneak through the thermal resistor 54 in the left channel 50L. For example, assume that only switch #2 in set 1L is turned off (i.e., open). Because switches #1, 3, 4 are on (i.e., closed), the AC voltage generator 35 will apply voltage to electrode elements El, E3, E4. Thermal resistors Tl and T2 provide a path for current to flow from El to E2; thermal resistors T3 and T2 provide a path for current to flow from E3 to E2; and thermal resistors T4 and T2 provide a path for current to flow from E4 to E2. This is equivalent to a parallel combination of El, E3, and E4 wired in series with E2. Because the number of thermal resistors in this parallel combination increases linearly with the number of electrode elements 52, the current in the single thermal resistor E2 (which is wired in series with the parallel combination) can become large. Including the optional additional switch set 3L will enable the system to prevent power dissipation in this single thermal resistor E2 by closing the corresponding switch #2 in set 3L.

[0072] To accomplish this (in those embodiments that include the additional switch set 3L), the controller 34 can be programmed so that whenever a given one of the switches in set 1L is turned off, the corresponding switch in set 3L is turned on. This will prevent the thermal resistor 54 associated with the turned-off electrode element 52 from dissipating too much power, as described in the previous paragraph.

[0073] In those embodiments that include the additional switch set 3L, the same approach described above in connection with the left channel 50L is used to accomplish the individual bypassing of each of the thermal resistors 54 in the right channel 50R, except that switch set 3R is used instead of set 3L. Corresponding switch sets (not shown) are also provided for the other channels 50A, 50P, and a similar approach is used in those channels as well.

[0074] Figure 5 A second embodiment of a transducer array 150 is depicted that provides individual conductors for each individual electrode element 152 without causing a significant increase in the number of wires in each cable to a given transducer array, nor requiring active components to be located on or near the transducer array. As will be described below in connection with Figure 6 A fourth embodiment of a transducer array 150 is depicted that provides individual conductors for each individual electrode element 152 without causing a significant increase in the number of wires in each cable to a given transducer array, nor requiring active components to be located on or near the transducer array. As will be described below in connection with

[0075] Each transducer array 150 includes a plurality of electrode elements 152, which are labeled El through E9 for ease of reference. The electrode elements 152 are similar to the electrode elements 52 described above in connection with Figure 3 Embodiments. Separate conductors go from each of the electrode elements 152 to the connector 157 in this Figure 5 Embodiment. These conductors are numbered 1 through 9, just above the "wire dress" block 155, which gathers the separate conductors into a single cable 156. In some preferred embodiments, the electrical connection to each of the electrode elements 152 includes one or more traces on a flexible circuit and / or one or more conductive wires.

[0076] In some preferred embodiments, all of the capacitively coupled electrode elements 152 are held in place by a support structure 159, which is similar to the support structure 59 in Figure 3 Embodiments.

[0077] Each transducer array 150 also includes a plurality of thermistors 154, with one thermistor positioned at each of the electrode elements 152, so that the thermistors 154 can sense the temperature of the corresponding electrode elements 152. This can be accomplished as described above in Figure 3 Embodiments. Each of the thermistors 154 has a first terminal (i.e., the lower terminal of the thermistor in Figure 5 ) and a second terminal (i.e., the upper terminal of the thermistor in Figure 5 ).

[0078] Each transducer array 150 also has a connector 157 for sending electrical signals to and from the transducer array 150. The connector 157 has a plurality of first pins, and a second pin. In the illustrated embodiment, the number of first pins is the same as the number of electrode elements 152, and each of the first pins corresponds to a respective one of those electrode elements 152. And in the illustrated embodiment, there is only a single second pin, labeled N. It should be noted that, as used herein, the term "pin" can refer to either male or female pins of the connector 157.

[0079] Each transducer array 150 also has a plurality of first conductors, and the number of these first conductors will depend on the number of electrode elements 152. In the embodiment depicted in Figure 5 , which contains 9 electrode elements 152, these conductors are labeled 1 through 9. Each of these first conductors provides an electrically conductive path between: (a) a respective one of the first pins in the connector 157, (b) the electrically conductive substrate of a respective one of the electrode elements 152 (El through E9), and (c) the first terminal of the corresponding thermistor 154. As with the embodiment described above in Figure 3In the embodiments, each of these first conductors may optionally be implemented using multiple wire segments and / or multiple traces on a flexible circuit.

[0080] Multiple thermal resistors 154 are arranged in series, starting with the first of the thermal resistors (i.e., Figure 5 (upper left of the middle) and terminates at the last one in the thermal resistor (i.e., Figure 5 (Lower right of center). The second terminal of each of the thermal resistors, except the last one, is wired to the first terminal of the corresponding next thermal resistor.

[0081] Each converter array 150 has a second conductor, which connects to the second terminal of the last thermal resistor 154 at the second pin of connector 157 (i.e., Figure 5 A conductive path is provided between the upper terminals of the lower right thermal resistor. The second conductor can optionally be implemented using multiple wire segments and / or multiple traces on a flexible circuit.

[0082] Because connector 157 has a separate first pin corresponding to each of the individual electrode elements 152, and because a conductive path exists between each of the first pins and the corresponding one of the electrode elements 152, a system mating with connector 157 can selectively supply power to or not supply power to each of the electrode elements 152 by applying or not applying a signal to the corresponding first pin on connector 157. Furthermore, because the two terminals of any given one of the thermal resistors 154 are wired to different pins on connector 157, a system mating with connector 157 can access both terminals of each of the thermal resistors 154. Therefore, a system mating with connector 157 can measure the resistance of any of the electrode elements in the thermal resistors 154.

[0083] It is worth noting that because any given first pin on connector 157 corresponds to one or both of the individual electrode elements 152 and also to one of the individual thermal resistors 154, each of the first pins on connector 157 provides two functions. This reduces the number of wires that must be included in each of the cables 156, which in turn advantageously increases the flexibility of the cables and reduces their cumbersome nature.

[0084] Figure 6 It uses four copies of converter array 150 (combined with the above). Figure 5 A block diagram of the system described to apply a TT field to the subject. Figure 6 In the diagram, these four copies are labeled 150A, 150P, 150L, ​​and 150R, where A, P, L, and R represent the front, rear, left, and right sides, respectively. Figure 6The lower portion of FIG. 1 depicts AC voltage generator 35 and "CAD box" 130 as separate blocks, with the latter including temperature measurement block 132, controller 134, and switch sets 1L, 2L, 3L, 1R, 2R, and 3R. In some embodiments, the elements in those two blocks 35, 130 can be physically partitioned into two separate housings. But in alternative embodiments, the elements in those two blocks 35, 130 are combined into a single housing.

[0085] For purposes of clarity, Figure 6 Only the left and right channels are depicted in FIG. 1. But the remaining channels (i.e., the front and back channels) operate in the same manner as the left and right channels, respectively. Also, for purposes of clarity, Figure 6 Each of the transducer arrays 150 in FIG. 1 is depicted as having only 4 electrode elements 152 and four thermal resistors 154. But it is contemplated that the actual system will have a larger number (e.g., between 9 and 30) of electrode elements and thermal resistors, depending on the number of electrode elements 152 actually used in each of the transducer arrays 150, and will also have a larger number of certain other elements (e.g., switches, conductors, etc.).

[0086] Figure 6 The system of FIG. 1 can measure the temperature of the thermal resistors 154 in the left channel 150L by sequentially selecting each of the thermal resistors using the electronically controlled switches in sets 2L and 3L, which can be implemented using bi-directional analog switches. For example, switches 1 and 2 should be closed to select thermal resistor Tl; switches 2 and 3 should be closed to select thermal resistor T2; switches 3 and 4 should be closed to select thermal resistor T3; and switches 4 and N should be closed to select the last thermal resistor (i.e., T4 in FIG. 1). Figure 6 After any given one of the thermal resistors Tl to T4 within transducer array 150L has been selected, temperature measurement block 132 can determine the temperature of the thermal resistor by measuring the resistance of the thermal resistor, as described above in connection with Figure 4 FIG. 1.

[0087] Measuring the temperature of the thermal resistors 154 in the right channel 150R is accomplished using the same method described above in connection with the left channel 150L, except that switch sets 2R and 3R are used instead of sets 2L and 3L. Corresponding switch sets (not shown) are also provided for the other channels 150A, 150P, and similar methods are used in those channels as well.

[0088] Based on the temperature readings obtained from the thermal resistors 154 (Tl to T4), controller 134 controls the switches in sets 1L and 1R (and corresponding switches in the front and back channels, not shown) to select the appropriate thermal resistors for the left and right channels, as described above in connection with Figure 4The described turning on or off of current to each of the corresponding electrode elements 152 (E1-E4), which originates from the AC voltage generator 35. For example, in order to have the current of all four electrode elements 152 in the on state, all four switches in group 1L should be closed. In order to interrupt the current to electrode element E1 in channel 150L, switch 1 in group 1L should be opened; and in order to interrupt the current to electrode element E2, switch 2 in group 1L should be opened; and so on.

[0089] Controlling the current routed through the individual electrode elements as described above can be used to reduce or eliminate the above-described Figure 4 coupling to the average current in the personal body when a small number of electrode elements start to overheat (e.g., by reducing the duty cycle of the specific electrode element).

[0090] Figure 7 is a schematic diagram of a circuit adapted to implement the above-described Figure 4 and Figure 6 embodiments in each of the switches in group 1L and 1R, and the corresponding groups of the front and back channels (not shown). The circuit includes two field effect transistors 66, 67 wired in series, which are configured to pass current in either direction. One example of a suitable FET for this circuit is the BSC320N20NSE. (Note that the diodes depicted in Figure 7 are essentially included within the FETs 66, 67 themselves.) The series combination of the two FETs 66, 67 will either conduct or block the flow of power, depending on the state of the control input arriving from one of the digital outputs of the above-described controller 34. When the series combination is on, current can flow between the shared conductor and the corresponding electrode element 52. On the other hand, when the series combination of FETs 66, 67 is off, current will not flow between the shared conductor and the corresponding electrode element 52.

[0091] In the above-described embodiments in connection with Figure 3 and Figure 5 all of the electrode elements 52 are capacitively coupled, and the support structure 59 is configured to hold the electrode elements 52 against the body of the subject such that the dielectric layer of the electrode elements 52 faces the body of the subject and can be positioned in contact with the body of the subject. But in alternative embodiments, electrode elements that are not capacitively coupled can be used. In this case, the dielectric layer of each electrode element is omitted, in which case the support structure 59 holds the electrode elements 52 against the body of the subject, so that the conductive surface of the electrode elements 52 faces the body of the subject and can be positioned in contact with the body of the subject. Optionally, in these embodiments, a hydrogel layer can be disposed between the conductive surface of the electrode elements 52 and the body of the subject when the transducer array 50 is placed against the body of the subject.

[0092] While the application has been disclosed with reference to certain embodiments, numerous modifications, alterations, and changes to the described embodiments are possible without departing from the sphere and scope of the application, as defined in the appended claims. Accordingly, it is intended that the application not be limited to the described embodiments, but that the full scope of the application be defined by the language of the following claims, and their equivalents.

Claims

1. A device for applying an alternating electric field to the body of a subject, the device comprising: Multiple electrode elements; A support structure configured to hold the electrode elements against the subject's body; Multiple thermal resistors, each having a first terminal and a second terminal, wherein each thermal resistor is positioned to sense the temperature at a corresponding electrode element in one of the electrode elements; A connector having multiple first pins and second pins; A plurality of first conductors, each of which provides a conductive path between (a) a corresponding one in a first pin, (b) a corresponding one in an electrode element, and (c) a first terminal of a corresponding thermal resistor; as well as The second conductor provides a conductive path between the second pin and the second terminal of at least one of the thermal resistors.

2. The apparatus according to claim 1, wherein, The second terminals of all thermal resistors are wired together.

3. The apparatus according to claim 2, wherein, The second terminals of all thermal resistors are wired together using at least one of (a) a flexible circuit and (b) at least one wire.

4. The apparatus according to claim 1, wherein, The plurality of thermal resistors are arranged in series, starting with the first thermal resistor and ending with the last thermal resistor, wherein the second terminal of each of the thermal resistors except the last one is wired to the first terminal of the corresponding subsequent thermal resistor, and wherein a second conductor provides a conductive path between the second pin of the connector and the second terminal of the last thermal resistor.

5. The apparatus according to claim 1, wherein, The second conductor provides a conductive path between the second pin and the second terminal of only one of the thermal resistors.

6. The apparatus according to claim 1, wherein, The plurality of electrode elements includes at least four electrode elements, and wherein the plurality of thermal resistors includes at least four thermal resistors.

7. The apparatus according to claim 1, wherein, The plurality of electrode elements includes at least nine electrode elements, and wherein the plurality of thermal resistors includes at least nine thermal resistors.

8. The apparatus according to claim 1, wherein, Each of the electrode elements includes a conductive plate and a dielectric layer disposed on the conductive plate, wherein a support is configured to hold the electrode element against the body of the subject, such that the dielectric layer of each of the electrode elements faces the body of the subject.

9. The apparatus according to claim 1, wherein, The second terminals of all thermal resistors are wired together, and a second conductor provides a conductive path between the second pin and the second terminals of all thermal resistors.

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