Array for providing tumor therapeutic electric fields (TTFIELDS) with selectively addressable sub-elements

Abstract

To provide an array for delivering tumor treatment fields (TTFields) with selectively addressable sub-elements.SOLUTION: Tumor treatment fields (TTFields) can be delivered to a subject's body at higher field strengths by switching off one or more electrode elements that are overheating without switching off other electrode elements that are not overheating. This may be accomplished using a plurality of temperature sensors, each of which is positioned to sense the temperature at individual electrode elements, and a plurality of electrically controlled switches, each of which is wired to switch the current to an individual electrode element on or off. A controller inputs signals from the temperature sensors to determine the temperature at each of the electrode elements, and controls the state of the control input of each of the electrically controlled switches to selectively switch off the current or adjust the duty cycle at any electrode element that is overheating.SELECTED DRAWING: Figure 3

Description

Technical Field

[0001] The present invention relates to an array for providing Tumor Treatment Fields (TTFields) having selectively addressable sub-elements.

Background Art

[0002] Tumor Treatment Fields (TTFields) treatment is a proven technique for primary treatment. FIG. 1 is a schematic diagram of a prior art Optune® system for providing TTFields. TTFields are provided to a patient via four transducer arrays 21-24 disposed on the patient's skin proximate the tumor (such as shown in FIGS. 2A-2D for a human having glioblastoma). Transducer arrays 21-24 are arranged in two pairs, and each transducer array is connected to an AC signal generator 20 via a multi-wire cable. The AC signal generator sends (a) during a first period, an AC current inducing an electric field having a first direction through the tumor via one pair of arrays 21, 22, and then (b) during a second period, an AC current inducing an electric field having a second direction through the tumor via the other pair of arrays 23, 24, and then repeats steps (a) and (b) during the treatment period.

[0003] Each transducer array 21-24 is configured as a set of capacitively coupled electrode elements E interconnected via flexible wires (e.g., a set of nine electrode elements each having a diameter of about 2 cm). Each electrode element includes a ceramic disk sandwiched between a layer of conductive medical gel and an adhesive tape. When the array is placed on the patient, the medical gel conforms to the irregularities of the patient's skin, ensuring good electrical contact between the device and the body. The adhesive tape secures the entire array to the patient so that the patient can go about their daily life.

[0004] The strength of the alternating current delivered through the transducer array is controlled so as not to exceed a safety threshold of 41°C for skin temperature (measured on the skin beneath the transducer array). Patient skin temperature is obtained using thermistors T positioned beneath some of the disks in the transducer array. In existing Optune® systems, each array contains eight thermistors, with one thermistor positioned beneath each disk in the array (it should be noted that most arrays contain more than eight disks, in which case temperature measurements are performed only beneath a subset of the array's disks).

[0005] The AC signal generator 20 obtains temperature readings from all 32 thermistors (8 thermistors per 4 arrays). The AC signal generator's controller uses these temperature readings to control the current delivered through each pair of arrays to maintain the temperature below 41°C on the patient's skin. The current itself is delivered to each array via additional wires connecting the AC signal generator 20 to each array (i.e., one wire 28 for each of arrays 21 through 24). [Overview of the Initiative] [Means for solving the problem]

[0006] One aspect of the present invention relates to a first apparatus for applying an alternating electric field to the body of a subject. The first apparatus includes a plurality of capacitively coupled electrode elements, each having a dielectric layer, and a support configured to hold the plurality of electrode elements such that the dielectric layers of the electrode elements can be positioned to contact the body of a subject. The first apparatus also includes a plurality of temperature sensors. Each of the plurality of temperature sensors is arranged to sense the temperature at each electrode element and generate a signal representing the sensed temperature. The first apparatus also includes a conductor and a plurality of electrically controlled switches. Each of the switches is configured to (a) allow current to flow between the conductor and each electrode element, or (b) prevent current from flowing between the conductor and each electrode element, depending on the state of each control input. The first apparatus also includes a controller configured to control the state of each control input of the switches.

[0007] In some embodiments of the first apparatus, the controller is further configured to receive each signal representing the sensed temperature from each of the temperature sensors, determine a duty cycle on which a given electrode element should be driven based on the received signals, and periodically switch the state of the control input of a switch corresponding to a given electrode element at the determined duty cycle so as to periodically prevent current from flowing between the conductor and the given electrode element.

[0008] In some embodiments of the first apparatus, the controller is further configured to receive each signal representing the sensed temperature from each temperature sensor, determine based on the received signals whether the temperature at each electrode element exceeds an upper threshold, and, if it is determined that the temperature at a given electrode element exceeds an upper threshold, control the state of the control input to each switch to prevent current from flowing between the conductor and the given electrode element. Optionally, in these embodiments, the controller is further configured to determine, based on the signals received from each temperature sensor, whether the temperature at each electrode element has fallen below a lower threshold after controlling the state of the control input to the given switch to prevent current from flowing between the conductor and each electrode element, and subsequently control the state of the control input to the given switch to allow current to flow between the conductor and each electrode element.

[0009] In some embodiments of the first device, the controller is further configured to receive signals from each of the temperature sensors, transmit data representing the temperature at each of the temperature sensors to a second controller, receive data from the second controller indicating which of the switches should be turned off, and control the state of the control inputs of the multiple switches based on the data received from the second controller.

[0010] In some embodiments of the first apparatus, the plurality of capacitively coupled electrode elements include at least nine capacitively coupled electrode elements. In some embodiments of the first apparatus, each of the capacitively coupled electrode elements includes a conductive plate having a flat surface, and a dielectric layer is disposed on the flat surface of the conductive plate. In some embodiments of the first apparatus, the support includes a foam layer. In some embodiments of the first apparatus, the conductor includes trace wiring of a flexible circuit.

[0011] In some embodiments of the first apparatus, the support is configured to hold a plurality of electrode elements with the dielectric layers of the electrode elements facing the subject's body to the external surface of the subject's body. In some embodiments of the first apparatus, a plurality of electrically controlled switches and controllers are arranged in a module attached to the support via a plurality of conductor connectors.

[0012] Another aspect of the present invention relates to a second apparatus for applying an alternating electric field to the body of a subject. The second apparatus includes a plurality of capacitively coupled sets of at least two electrode elements, each electrode element having a dielectric layer, and a support configured to hold the plurality of sets of electrode elements such that the dielectric layers of the electrode elements can be positioned to contact the body of a subject. The second apparatus also includes a plurality of temperature sensors. Each temperature sensor is arranged to sense the temperature in each set of electrode elements and to generate a signal representing the sensed temperature. The second apparatus also includes a conductor and a plurality of electrically controlled switches. Each switch is configured to (a) allow current to flow between the conductor and each electrode element, or (b) prevent current from flowing between the conductor and each electrode element, depending on the state of each control input. The second apparatus also includes a controller configured to control the state of each control input of the switches.

[0013] In some embodiments of the second apparatus, all electrode elements within any given set of electrode elements are arranged concentrically.

[0014] In some embodiments of the second apparatus, the controller is further configured to receive each signal representing the sensed temperature from each of the temperature sensors, determine a duty cycle on which a given electrode element should be driven based on the received signals, and periodically switch the state of the control input of a switch corresponding to the given electrode element at the determined duty cycle so as to periodically prevent current from flowing between the conductor and the given electrode element.

[0015] In some embodiments of the second apparatus, the controller is further configured to receive each signal representing the sensed temperature from each of the temperature sensors, determine based on the received signals whether the temperature in each set of electrode elements exceeds an upper threshold, and, if it is determined that the temperature in a given set of electrode elements exceeds an upper threshold, to control the state of the control input of at least one of each switch to prevent current from flowing between the conductor and at least one of the electrode elements in the given set of electrode elements.

[0016] In some embodiments of the second device, the controller is further configured to receive signals from each of the temperature sensors, transmit data representing the temperature at each of the temperature sensors to the second controller, receive data from the second controller indicating which switches should be turned off, and control the state of the control inputs of the multiple switches based on the data received from the second controller.

[0017] In some embodiments of the second apparatus, the support is configured to hold multiple sets of electrode elements such that the dielectric layers of the electrode elements face the subject's body with respect to the subject's external surface. In some embodiments of the second apparatus, multiple electrically controlled switches and controllers are arranged in modules attached to the support via multiple conductor connectors.

[0018] Another aspect of the present invention relates to a third apparatus for applying an alternating electric field to the body of a subject. The third apparatus includes a plurality of first electrode elements and a flexible support configured to hold the plurality of first electrode elements against the body of a subject. The third apparatus also includes a plurality of temperature sensors. Each temperature sensor is arranged to sense the temperature at each first electrode element and generate a signal indicating the sensed temperature. The third apparatus also includes a conductor and a plurality of electrically controlled first switches. Each of the first switches is wired in series with each first electrode element in a circuit that begins at the conductor and ends at each of the first electrode elements, and each of the first switches is configured to switch on or off independently of the other first switches based on the state of each control input. The third apparatus also includes a controller configured to generate an output that determines the state of the control input with respect to each of the first switches.

[0019] In some embodiments of the third apparatus, each of the first electrode elements includes a capacitively coupled electrode element having a dielectric layer, and a flexible support is configured to hold a plurality of first electrode elements relative to the subject's body such that the dielectric layers of the first electrode elements face the subject's body.

[0020] Some embodiments of the third apparatus further include a plurality of second electrode elements, each of which is positioned adjacent to each of the first electrode elements, and a plurality of electrically controlled second switches. Each of the second switches is wired in series with each of the second electrode elements in a circuit that begins with a conductor and ends with each of the second electrode elements, and each of the second switches is configured to switch on or off independently of the other second switches based on the state of each control input. A support is configured to hold the plurality of second electrode elements against the body of a subject. A controller is further configured to generate an output that determines the state of the control input with respect to each of the second switches.

[0021] Optionally, in these embodiments, each of the first electrode elements includes a capacitively coupled electrode element having a dielectric layer, each of the second electrode elements includes a capacitively coupled electrode element having a dielectric layer, and the support is configured to (a) hold a plurality of first electrode elements against the body of the subject with the dielectric layer of the first electrode element facing the body of the subject, and (b) hold a plurality of second electrode elements against the body of the subject with the dielectric layer of the second electrode element facing the body of the subject.

[0022] Optionally, in these embodiments, each of the second electrode elements is concentric with each adjacent first electrode element.

Brief Description of the Drawings

[0023] [Figure 1] Schematic diagram of a prior art Optune® system for providing TTFields. [Figure 2A] Shows the placement of a transducer array on a human head for treating brain tumors. [Figure 2B] Shows the placement of a transducer array on a human head for treating brain tumors. [Figure 2C] Shows the placement of a transducer array on a human head for treating brain tumors. [Figure 2D] Shows the placement of a transducer array on a human head for treating brain tumors. [Figure 3] Shows a first embodiment in which the on or off of the current to each individual electrode element can be switched based on the state of a set of electrically controlled switches. [Figure 4] Schematic diagram of a mechanical layout that can be used for one of the transducer assemblies shown in FIG. 3. [Figure 5] Shows an alternative configuration in which transducer elements are grouped into n sets and a single temperature sensor is used to measure the temperature for each of these n sets. [Figure 6]It is a schematic diagram of a circuit suitable for realizing a switch in the embodiments of FIGS. 3 to 5.

Embodiments for Carrying Out the Invention

[0024] Various embodiments are described in detail below with reference to the accompanying drawings, and like reference numerals represent like elements.

[0025] The prior art method described above with respect to FIG. 1 is very effective in providing TTFields to tumors, but the therapeutic effect will decrease if good electrical contact is not maintained between each of the elements of the four transducer arrays 21 to 24 and the human body. This can occur, for example, when the hydrogel under one or more elements of the transducer array dries over time or due to body hair growing under one or more elements.

[0026] For example, in a prior art system having nine electrode elements E in each of the transducer arrays 21 to 24, assume that the hydrogel under a single electrode element E of the front transducer array 21 has dried, and (a) all of the other electrode elements E of that transducer array 21, and (b) assume that there is sufficient hydrogel under all of the electrode elements E of the other transducer arrays 22 to 24. In this situation, the resistance between the single electrode element E and the human body will be higher than the resistance between any of the other electrode elements and the human body. And this increase in resistance will cause the temperature of the single electrode element E to rise more than that of the other electrode elements.

[0027] In this situation, the prior art AC signal generator 20 must limit the current applied to the front / rear pair of transducer arrays 21, 22 in order to maintain the temperature of a single electrode element E of the front array 21 below 41°C, even if the temperatures of all of the remaining electrode elements E of the front and rear transducer arrays 21, 22 are well below 41°C. And this decrease in current will cause a corresponding decrease in the strength of the electric field in the tumor.

[0028] The embodiments described herein can be used to minimize or eliminate the reduction in current bound to the human body, thereby minimizing or eliminating the reduction in the intensity of the electric field in a tumor. This can be achieved by alternately switching the current on and off for each individual electrode element that is beginning to approach 41°C, thereby reducing the average current for these electrode elements without affecting the current passing through the remaining electrode elements (which are not approaching 41°C).

[0029] For example, suppose a current of 500mA is passing through a transducer array containing 10 electrode elements, and only one of these electrode elements is beginning to reach 41°C. Furthermore, suppose that in order to maintain the temperature of that single electrode element below 41°C, it is necessary to reduce the current passing through that single electrode element by 10%. Rather than achieving this 10% reduction in current by cutting the current through the entire transducer array from 500mA to 450mA (as in the prior art), the embodiments described herein can reduce the average current passing through a single electrode element by 10% while keeping the current through all the remaining electrode elements at full time by switching the current passing through the single electrode element on and off at a 90% duty cycle. From the standpoint of the thermal inertia of the electrode elements, the switching rate must be fast enough so that the instantaneous temperature of the single electrode element never exceeds 41°C. For example, a 90% duty cycle can be achieved by switching the current on for 90ms and then off for 10ms. In some preferred embodiments, the time period for switching the current on and off is less than 1 second.

[0030] When this method is used, the current passing through the remaining nine electrode elements can remain unchanged (i.e., 50 mA per electrode element), and only the current passing through a single electrode element is reduced to an average of 45 mA. In this case, the average net total current passing through the transducer array is 495 mA (i.e., 9 × 50 + 45), which means that a sufficiently large current can be bonded to the human body without any of the electrode elements exceeding 41°C.

[0031] The system may also be configured to increase the current through the remaining nine electrode elements to compensate for the decrease in current through a single electrode element. For example, the current through the remaining nine electrode elements may be increased to 50.5 mA per electrode element (e.g., by sending a request to the AC voltage generator to increase the voltage by 1%). If this solution is implemented, the average net total current through the entire transducer array will be (9 electrodes × 50.5 mA + 1 electrode × 50.5 mA × 0.9 duty cycles) = 499.95 mA, which is very close to the original 500 mA current.

[0032] If, at some point thereafter (or simultaneously), the temperature of the second electrode element begins to approach 41°C, a similar technique (i.e., reducing the duty cycle from 100% to less than 100%) may be used to prevent the temperature of the second electrode element from exceeding 41°C.

[0033] In some embodiments, this technique can be used to individually customize the duty cycle of each electrode element, maximizing the current flowing through each of these electrode elements while maintaining the temperature of each electrode element below 41°C. Optionally, instead of employing an improved approach of reducing the duty cycle only when the temperature of a given electrode element begins to approach 41°C, the system can be configured to individually and proactively set the duty cycle of each electrode element in a given transducer array so that the temperature is equal across all electrode elements in the array. For example, the system can be configured to individually set the duty cycle of each electrode element so that each electrode element maintains a temperature of around 40.5°C. Optionally, the system can be configured to send a request to the AC voltage generator to increase or decrease the voltage as needed to achieve this result.

[0034] This technique can be used to ensure that each and all electrode elements can achieve the maximum average current (without exceeding 41°C), which will result in increased electric field intensity in tumors and corresponding improvements in treatment.

[0035] Figure 3 shows a first embodiment in which the current is periodically switched on and off for each individual electrode element that is beginning to approach 41°C. The AC signal generator has two outputs (OUT1 and OUT2), each with two terminals. The AC signal generator 30 generates an AC current (e.g., a 200 kHz sine wave) alternately (e.g., alternately activating OUT1 for 1 second, then activating OUT2 for 1 second) between the two terminals of each of these outputs. A pair of conductors 51 are connected to the two terminals of OUT1, each of which points to the left and right transducer assemblies 31, 32, respectively. A second pair of conductors 51 are connected to the two terminals of OUT2, each of which points to the front and rear transducer assemblies (not shown), respectively. The construction and operation of the front and rear transducer assemblies are similar to the construction of the left and right transducer assemblies 31, 32 shown in Figure 3.

[0036] Each of the transducer assemblies 31 and 32 includes a plurality of electrode elements 52. In some preferred embodiments, each of these electrode elements 52 is a capacitively coupled electrode element, similar to the conventional electrode elements used in Optune® systems. However, in the embodiment shown in Figure 3, instead of wiring all the electrode elements 52 in parallel, electrically controlled switches (S) 56 are wired in series with each electrode element (E) 52, and all of these S+E combinations 56+52 are wired in parallel. Each of the switches 56 is configured to switch on or off independently of the other switches based on the state of each control input arriving from the digital output of each controller 85. When one of the switches 56 is on (depending on the first state of each control input), current can flow between the conductor 51 and each electrode element 52. Conversely, when one of the switches 56 is off (depending on the second state of each control input), current cannot flow between the conductor 51 and each electrode element 52.

[0037] In some preferred embodiments, each of the capacitively coupled electrode elements 52 is disc-shaped (for example, having a diameter of 2 cm) and has a dielectric layer on one side. The transducer assemblies 31, 32 hold the electrode elements 52 against the subject's body with the dielectric layers of the electrode elements facing the subject's body. Preferably, if the transducer assemblies 31, 32 are positioned against the subject's body and capable of holding the electrode elements 52 against the subject's body, a layer of hydrogel is placed between the dielectric layers of the electrode elements and the subject's body.

[0038] In some preferred embodiments, each of the capacitively coupled electrode elements 52 includes a conductive plate having a flat surface, and the dielectric layer is disposed on the flat surface of the conductive plate. In some preferred embodiments, all of the capacitively coupled electrode elements are fixed by a support structure. Optionally, this support structure may include a foam layer. In some preferred embodiments, the electrical connections to each of the electrode elements 52 include trace wiring of a flexible circuit.

[0039] Each of the transducer assemblies 31 and 32 also includes a temperature sensor 54 (e.g., a thermistor) positioned on each of the electrode elements 52, each of which is capable of sensing the temperature of each electrode element 52. Each of the temperature sensors 54 generates a signal indicating the temperature (e.g., below) at each electrode element 52. The signals from the temperature sensors 54 are provided to the analog front of each controller 85.

[0040] In embodiments where thermistors are used as temperature sensors 54, temperature readings can be obtained by routing a known current through each thermistor and measuring the voltage that appears across each thermistor. In some embodiments, thermistor-based temperature measurement may be implemented using a bidirectional analog multiplexer to select each of the thermistors, and having a current source located behind the multiplexer that generates a known current (e.g., 150 μA), so that the known current is routed to any thermistor selected by the analog multiplexer at any given moment. The known current generates a voltage across the selected thermistors, and the temperature of the selected thermistors can be determined by measuring this voltage. Controller 85 runs a program to select each of the thermistors and measure the voltage that appears across each of the thermistors (representing the temperature at the selected thermistor). Examples of suitable hardware and procedures that may be used to obtain temperature readings from each of the thermistors are described in U.S. Patent Application Publication No. 2018 / 0050200, which is incorporated herein by reference in its entirety.

[0041] In some preferred embodiments, the controller 85 may be implemented using a single-chip microcontroller or a programmable system-on-chip (PSoC) with an integrated analog front-end and multiplexer. A suitable part number for this purpose includes CY8C4124LQI-443. In alternative embodiments, as will be apparent to those skilled in the art, another microcontroller may be used, having an integrated or discrete analog front-end and multiplexer.

[0042] In alternative embodiments, although not shown, alternative methods for interfacing with the thermistor (e.g., conventional voltage divider methods) may be used instead of the constant current method described above. In other alternative embodiments, different types of temperature sensors may be used instead of the thermistor described above. Examples include thermocouples, RTDs, and integrated circuit temperature sensors such as Analog Devices' AD590 and Texas Instruments' LM135. Of course, in the event that any of these alternative temperature sensors is used, appropriate modifications to the circuit (which will be obvious to those skilled in the art) will be necessary.

[0043] In some embodiments, the controller 85 is programmed to maintain the temperature of all electrode elements below a safe threshold (e.g., below 41°C) using intelligence built into each transducer assembly 31. This can be achieved, for example, by programming the controller 85 to begin by setting its digital output so that each of the switches 56 is continuously on (i.e., a 100% duty cycle). Then, based on signals arriving via the analog front end of the controller 85, the controller 85 determines whether the temperature of each electrode element exceeds an upper threshold (e.g., 40°C) below the safe threshold. When the controller 85 detects this condition, it reduces the duty cycle of the corresponding switch 56 by toggling the corresponding digital output at a desired duty cycle. This cuts off the current to the corresponding electrode element 52 at the same duty cycle, thereby reducing the average current at the particular electrode element whose temperature exceeds the upper threshold. The level of reduction in current is determined by the duty cycle. For example, using a 50% duty cycle cuts the current in half, while using a 75% duty cycle cuts the current by 25%.

[0044] In particular, this procedure interrupts the current to only one specific electrode element 52 of the transducer assembly 31, and does not interrupt the current to the remaining electrode elements 52 of the transducer assembly 31. This provides a significant advantage over the prior art by eliminating or reducing the need to cut off the current routed through the electrode elements when only a few of these electrodes are heated.

[0045] A numerical example is useful to illustrate this point. In the embodiment shown in Figure 3, left and right transducer assemblies 31 and 32 are positioned on the left and right sides of the subject's head, respectively, and all switches 56 on transducer assemblies 31 and 32 are ON with a 100% duty cycle, and the AC signal generator 30 is initially outputting a current of 500 mA to the conductor 51. The AC voltage appears between the electrode element 52 of the left transducer assembly 31 and the electrode element 52 of the right transducer assembly 32, and the 500 mA AC current is capacitively coupled through the electrode element 52 through the subject's head. The controller 85 of each transducer assembly 31 and 32 monitors the temperature of each electrode element 52 in its transducer assembly by receiving signals from each of the temperature sensors 54 via the analog front end of the controller 85. Now, suppose the temperature of one of the electrode elements 52 of transducer assembly 31 has risen to 40°C. This situation is reported to the controller 85 in the transducer assembly 31 via a signal from the corresponding temperature sensor 54. When the controller 85 recognizes that the temperature of a given electrode 52 has risen to 40°C, the controller 85 toggles a control signal to the corresponding switch 56 at a desired duty cycle to periodically cut off the current to the given electrode element 52 and maintain a low average current.

[0046] This is in stark contrast to conventional devices, where if even one of the electrode elements 52 approached 41°C, the current flowing through all the electrode elements had to be immediately reduced.

[0047] It should be noted that if the duty cycle of only one of the remaining electrode elements 52 is reduced, the original 500mA current may be maintained (and the benefits of using the full current may be enjoyed). However, if the duty cycle of a sufficiently large number of electrode elements 52 is reduced, the original 500mA current may have to be reduced. To achieve this, the controller 85 can send a request to the AC signal generator via the controller 85's UART. When the AC signal generator 30 receives this request, the AC signal generator 30 will reduce the output current at the corresponding output OUT1.

[0048] Optionally, the duty cycle selected by the controller 85 may 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 sensor 54 and the analog front end of the controller 85). More specifically, if the controller 85 recognizes that a given electrode element 52 is heating up twice as fast as expected, the controller 85 can select a 50% duty cycle for that electrode element. Similarly, if the controller 85 recognizes that a given electrode element 52 is heating up 10% faster than expected, the controller 85 can select a 90% duty cycle for this electrode element.

[0049] In other embodiments, instead of definitively cutting the average current by reducing the duty cycle, the controller 85 can reduce the average current at a given electrode element 52 based on real-time temperature measurements by turning off the current to the given electrode element 52 and waiting until the temperature measured using the temperature sensor 54 drops to a second temperature threshold (e.g., below 38°C). Once the temperature drops below this second temperature threshold, the controller 85 can restore the current to the given electrode element 52. This may be achieved, for example, by controlling the state of the control input to a switch 56 that was previously turned off, so that the switch 56 returns to the ON state, thereby allowing current to flow between the conductor and each 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 so that the temperature at the given electrode element 52 can be kept below a safety threshold.

[0050] In the embodiment shown in Figure 3, each of the transducer assemblies 31 and 32 is connected to the AC signal generator 30 via their respective cables. In particular, only four conductors are required in each cable passing between the transducer assembly and the AC signal generator 30 (i.e., Vcc, data, and ground for serial data communication, plus one additional conductor 51 for the AC current TTFields signal).

[0051] In Figure 3, each of the transducer assemblies 31 and 32 includes nine electrode elements 52, nine switches 56, and nine temperature sensors 54. However, in an alternative embodiment, each of the transducer assemblies 31 and 32 may include a different number (e.g., between 8 and 25) of electrode elements 52, as well as a corresponding number of switches and temperature sensors.

[0052] Figure 4 is a schematic diagram of one mechanical layout that may be used with respect to any predetermined one of the left / right transducer assemblies 31, 32 shown in Figure 3, or the front / rear transducer assemblies 33, 34 (not shown in Figure 3) connected to the second output OUT2 of the AC signal generator 30 shown in Figure 3. In this embodiment, each transducer assembly 31 to 34 includes a plurality of electrostatically coupled electrode elements 52 mounted on a support 59. The electrode elements 52 are configured to be positioned against the subject's body (preferably with a layer of hydrogel placed on the surface of the electrode elements facing the subject's body), and the support 59 holds the plurality of electrode elements 52 against the subject's body such that the dielectric layers of the electrode elements 52 face the subject's body. The support 59 may preferably be flexible and may consist of a material such as cloth or high-density medical foam. An adhesive layer may be used to secure the support 59 to the human body. A temperature sensor 54 is positioned to sense the temperature at each of the electrode elements 52. For example, each temperature sensor 54 may be positioned adjacent to and / or below one of the corresponding electrode elements 52. In some embodiments, each electrode element 52 has a small hole in the center, and the temperature sensor 54 is positioned in that small hole. Although only two electrode elements 52 and their corresponding switches 56 and temperature sensors 54 are shown in Figure 4, it should be noted that more (e.g., between 9 and 25) of each of these components are preferably used. This is indicated in Figure 3 by the symbols E1···En, S1···Sn, and T1···Tn for each of the electrode elements, switches, and temperature sensors.

[0053] Module 60 is attached to the support 59 (either directly or through intervening components). Module 60 includes a controller 85 and a switch 56. Optionally, module 60 can be connected to the support 59 using a conductor 42, in which case half of the connector 42 is provided to module 60 and the engaging half of the connector 42 is provided to the support 59. When both halves of the connector 42 are engaged, the signal from the thermistor 54 passes through the connector 42 and the wiring on the support 59 (e.g., the wiring of the flexible circuit) to the controller 85 of module 60. Furthermore, AC current signals from each output side of the switch 56 are directed to each of the electrode elements 52 through the connector 42 and the wiring on the support 59 (e.g., the wiring of the flexible circuit).

[0054] Since the array of electrode elements 52 is preferably sterilized before use, including an optional connector 42 offers advantages over embodiments that do not include this connector. Sterilization is typically performed using either radiation or gas. Because such radiation can interfere with electronic equipment, only assemblies where the electronic equipment cannot be disconnected from the array of electrode elements 52 can be sterilized with gas. On the other hand, if the electronic components 56, 85 can be disconnected from the array of electrode elements 52 via the connector 42 (as shown in Figure 4), the electronic equipment can be connected after sterilization. This allows the array of electrode elements 52 to be sterilized using either gas or radiation without the risk of damaging the sensitive electronic components 56, 85.

[0055] As mentioned above, only four connectors are required for each of the cables passing between each of the transducer assemblies 31 to 34 and the AC signal generator 30 (i.e., Vcc, data, and ground for serial data communication, plus one additional conductor 51 for the AC current TTFields signal). In some preferred embodiments, the connection between the transducer assemblies 31 to 34 and the AC signal generator (shown in Figure 3) is connectorized, for example, using a conductor 38.

[0056] In the embodiments described above, the decision to adjust or turn off the duty cycle of one or more switches 56 of a given transducer assembly 31, 32 in order to reduce the average current to one or more electrode elements 52 may be made locally in each transducer assembly 31, 32 by a controller 85 within that transducer assembly 31, 32. However, in alternative embodiments, the decision to adjust or turn off the duty cycle of one or more switches 56 may be made by the AC signal generator 30 (or another remote device, such as a central hub located between the AC signal generator 30 and each of the transducer assemblies 31, 32). In these embodiments, the controller 85 in each transducer assembly 31, 32 obtains temperature readouts from each of the temperature sensors 54 in each transducer assembly and transmits these temperature readouts to the AC signal generator 30 via the controller 85's UART. The AC signal generator 30 determines, if any, which switches require duty cycle adjustment or should be turned off based on the received temperature readings, and transmits the corresponding commands to the corresponding controllers 85 of the corresponding transducer assemblies 31, 32. When the controller 85 receives this command from the AC signal generator 30, the controller 85 responds by setting its digital output to a state that switches off the corresponding switch 56 a suitable number of times in order to execute the command issued by the AC signal generator 30. In these embodiments, the AC signal generator 30 can also be programmed to reduce its output current if a reduction in current is necessary to keep the temperature of each electrode element 52 below a safety threshold.

[0057] In these embodiments, the controller 85 may be programmed to operate as a slave to a master controller located on the AC signal generator 30. In these embodiments, the controller 85 starts in a quiescent state and in this case simply monitors commands arriving from the master controller via UART. Examples of commands that can arrive from the master controller include the commands "collect temperature data", "transmit temperature data", and "set switch". When the controller 85 recognizes that the "collect temperature data" command has arrived, the controller 85 obtains temperature readouts from each of the temperature sensors 54 and stores the results in a buffer. When the controller 85 recognizes that the "transmit temperature data" command has arrived, the controller 85 performs the procedure of transmitting the previously collected temperature readouts from the buffer to the AC signal generator 30 via UART 86. Then, when the controller 85 recognizes that the "set switch" command has arrived, the controller 85 performs a procedure to output an appropriate voltage at its digital output to set each of the switches 56 to the desired state (i.e., on or off, or to switch between on and off at the commanded duty cycle) based on the data arriving from the AC signal generator 30.

[0058] In the embodiments described above, a single controller 85 is used in each of the transducer assemblies 31 and 32 to control the switches 56 of the assemblies and to obtain temperature readings from each of the temperature sensors 54 of the assemblies. In alternative embodiments, instead of using a single controller 85 to control the switches 56 and obtain temperature readings, these two tasks may be divided among two controllers, one used solely for controlling the switches 56 and the other for obtaining temperature readings from each of the temperature sensors 54 (e.g., using one of the methods described above). In these embodiments, these two controllers may communicate directly with each other and / or with the AC signal generator 30.

[0059] In other alternative embodiments (not shown), temperature measurements are not based on a local controller located near the electrode element 52. Instead, wiring runs from each of the temperature sensors 54 back to the AC signal generator 30 (or to a central hub located between the AC signal generator 30 and each of the transducer assemblies 31, 32), and the AC signal generator uses the signals arriving through these wiring to determine the temperature at each of the temperature sensors 54. However, in these embodiments, the cables leading to the transducer array require more conductors, which can reduce the flexibility of the cables and increase their complexity.

[0060] In the embodiments shown in Figures 3 and 4 above, the number of temperature sensors 54 corresponds to the number of electrode elements 52, and each temperature sensor 54 is specialized to sense the temperature of one of the electrode elements 52. Figure 5 shows an alternative configuration in which the electrode elements are grouped into n sets, and a single temperature sensor is used to measure the temperature of each of these n sets. In some preferred embodiments, n is between 9 and 25.

[0061] To achieve this, the electrode elements within any given set must be adjacent to one another. In the embodiment shown in Figure 5, each set includes an inner disk-shaped electrode element 52 similar to the electrode element described above with respect to Figure 4, in addition to an additional outer ring-shaped electrode element 52' surrounding and concentric with the inner disk-shaped electrode element 52. The temperature sensor 54 is positioned in the center of the inner disk-shaped electrode element 52. Each electrode element 52, 52' has its own individual switch 56, 56', which allows the controller 85 to switch the current on or off. In an alternative embodiment (not shown), an additional concentric ring-shaped electrode element may be added to each set. In another alternative embodiment (not shown), instead of arranging all the electrode elements of any given set in a concentric ring, the electrode elements of each set may be placed next to one another (for example, using electrode elements arranged in a slice-like pattern, with the temperature sensor in the center of this pie). In these alternative embodiments, each electrode element has its own switch so that the controller 85 can switch the current on or off individually.

[0062] The embodiment in Figure 5 can be operated to achieve the same results as described above in relation to Figures 3 and 4 by programming the controller 85 to always switch the current to all of any given set of electrode elements 52, 52' together on or off. However, this embodiment also provides additional flexibility. More specifically, if the controller 85 determines, based on a signal from one of the temperature sensors 54, that a high-temperature region exists within a given transducer assembly, the controller in this embodiment has the option to reduce the current in this high-temperature region by deactivating some, but not all, of the electrode elements corresponding to the high-temperature region. For example, suppose a signal from a first temperature sensor 54(T1) under a first set of electrodes 52, 52'(E1 / E1') reveals that the temperature under that set of electrodes has risen to 40°C or higher. The controller 85 in this embodiment in Figure 5 has the option to reduce the current in this region by issuing a command to turn off only some of the corresponding switches. This can be achieved, for example, by turning off the switch S1 supplying the inner element E1 and leaving the switch S1' supplying the outer element E1' on. Alternatively, the same result can be achieved by turning off the switch S1' supplying the outer element E1' and leaving the switch S1 supplying the inner element E1 on.

[0063] Optionally, to obtain additional control over the average current coupled through any of the regions described above with respect to Figures 3 and 4, the duty cycle for each individual electrode element of any set of electrode elements in the embodiment of Figure 5 can be individually adjusted.

[0064] Although only two sets of electrode elements 52, 52' and their corresponding switches 56, 56' and temperature sensors 54, 54' are shown in Figure 5, it should be noted that more sets of these components (e.g., 9 to 25) are preferably used. These are represented by the symbols E1···En, E1'···En', S1···Sn, S1'···Sn', T1···Tn, and T1'···Tn' in Figure 5 for each of the electrode elements, switches, and temperature sensors.

[0065] Figure 6 is a schematic diagram of a suitable circuit for implementing the switches 56, 56' in the embodiments of Figures 3 to 5 described above. The circuit includes two field-effect transistors 66, 67 wired in series, which are configured to allow current to pass in either direction. One example of a suitable FET for this circuit is the BSC320N20NSE (the diode shown in Figure 6 is originally included in the FETs 66, 67 themselves). The series combination of the two FETs 66, 67 either allows current to pass or blocks it, depending on the state of the control input arriving from one of the digital outputs of the controller 85 described above. If the series combination is conductive, current can flow between the shared conductor 51 and each electrode element 52, 52'. On the other hand, if the series combination of FETs 66, 67 is not conductive, current does not flow between the shared conductor 51 and each electrode element 52, 52'.

[0066] Optionally, the current sensing circuit 60 may be placed in series with switches 56, 56'. The current sensing circuit 60 may be implemented using any of the various conventional methods that are apparent to those skilled in the art. If the current sensing circuit 60 is included, it generates an output representing the current, which is reported back to the controller 85 (shown in Figures 3 to 5). The controller 85 can use this information to determine whether the measured current is as expected and take appropriate action if necessary. For example, if an overcurrent condition is detected, the controller 85 can turn off the corresponding switch. Of course, in these embodiments where the current sensing circuit 60 is omitted, the shared conductor 51 should be replaced with wiring (or other conductors) to allow current to flow between it and the top leg of the upper FET 60.

[0067] In the illustrated embodiment, the current sensing circuit 60 is located between the shared conductor 51 and the top leg of the upper FET 60. However, in an alternative embodiment, the current sensing circuit may be located between the bottom leg of the lower FET 67 and the respective electrode elements 52, 52'. And in other alternative embodiments (not shown), the current sensing circuit may be integrated into the switch circuit itself.

[0068] Although the present invention has been disclosed with reference to specific embodiments, numerous improvements, substitutions, and variations to the described embodiments are possible without departing from the scope of the invention, as set forth in the appended claims. Therefore, the present invention is not to be limited to the described embodiments, but is intended to encompass the entire scope defined by the following claims and their equivalents. [Explanation of symbols]

[0069] 20 AC signal generators 21-24 transducer array 30 AC signal generators 31-34 Transducer Assembly 38 Conductors 42 Conductors, Connectors 43 Temperature sensor 51 Conductor 52 Electrode Elements 52' Outer ring-shaped electrode element 54 Temperature sensor 56, 56' switch 59 Support part 60 modules 66, 67 Field-effect transistors 85 Controllers

Claims

1. A plurality of sets of electrode elements, each set comprising at least a first electrode element and a second electrode element, A support unit configured to hold multiple sets of the electrode elements against the subject's body, A plurality of temperature sensors, each of which is arranged to sense the temperature in each of the sets of electrode elements and to generate a signal representing the sensed temperature, Conductors and, A plurality of electrically controlled switches, each of which is configured to either (a) allow current to flow between the conductor and each electrode element, or (b) prevent current from flowing between the conductor and each electrode element, depending on the state of each control input, A controller configured to control the state of each of the control inputs of the switches, In each of the set of electrode elements, the first electrode element and the second electrode element are arranged in a pie-like slice, and the second electrode element is positioned adjacent to each of the first electrode elements. Each of the temperature sensors is positioned adjacent to the first electrode element and the second electrode element in each of the set of electrode elements, and is located in the center of the pie shape formed by the first electrode element and the second electrode element. A device for applying an alternating electric field to a subject's body.

2. The apparatus according to claim 1, wherein the plurality of sets of electrode elements includes at least a set of nine electrode elements.

3. The apparatus according to claim 1, wherein the support portion includes a foam layer.

4. The apparatus according to claim 1, wherein the conductor includes trace wiring of a flexible circuit.

5. The aforementioned controller further, From each of the temperature sensors, the respective signals representing the detected temperature are received. Based on the received signal, the duty cycle over which the electrode element should be driven is determined. The electrode elements are driven by the determined duty cycle, and the state of the control input of the switch corresponding to each electrode element is periodically switched by the determined duty cycle to periodically prevent current from flowing between the conductor and each electrode element. The apparatus according to claim 1, configured as described above.

6. The aforementioned controller further, From each of the temperature sensors, the respective signals representing the detected temperature are received. Based on the received signal, it is determined whether the temperature in each set of electrode elements exceeds an upper threshold. If it is determined that the temperature in a predetermined set of electrode elements exceeds the upper threshold, the state of the control input of at least one of each of the switches is controlled to prevent current from flowing between the conductor and at least one of the electrode elements in the predetermined set of electrode elements. The apparatus according to claim 1, configured as described above.

7. The controller further controls the state of the control input to a predetermined switch so as to prevent current from flowing between the conductor and each electrode element, then determines, based on signals received from each temperature sensor, whether the temperature at each electrode element has fallen below a lower threshold, and subsequently controls the state of the control input to the predetermined switch so as to allow current to flow between the conductor and each electrode element. The apparatus according to claim 1, configured as described above.

8. The aforementioned controller further, Receiving signals from each of the aforementioned temperature sensors, The data representing the temperature in each of the temperature sensors is transmitted to the second controller. The second controller receives data indicating which switch should be turned off. Based on the data received from the second controller, the state of the control inputs of the plurality of switches is controlled. The apparatus according to claim 1, configured as described above.

9. The apparatus according to claim 1, wherein the plurality of electrically controlled switches and the controller are arranged in a module attached to the support portion via a plurality of conductor connectors.

10. Each of the aforementioned electrode elements includes a capacitively coupled electrode element having a dielectric layer, The apparatus according to claim 1, wherein the flexible support portion is configured to hold the plurality of sets of electrode elements against the subject's body such that the dielectric layer of the electrode element faces the subject's body.

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