Optimization of composite electrodes

Abstract

This paper describes an apparatus and method for applying an electric field through a target area within a patient's body. [Solution] The device includes a sensor array having a plurality of temperature sensors, wherein a plurality of first temperature sensors of the sensor array are connected to a first conductor, and a plurality of second temperature sensors are connected to a second conductor. The circuit is configured to supply a known amount of electricity to a third temperature sensor via the first and second conductors, the third temperature sensor being located within the plurality of first temperature sensors and the plurality of second temperature sensors.

Description

Technical Field

[0001] Cross - Reference to Related Applications / Incorporation by Reference Statement This patent application claims the priority of a provisional application identified by U.S. Serial No. 63 / 128,265, filed on December 21, 2020, the entire content of which is incorporated herein by reference.

[0002] Description of Research and Development Funded by the Federal Government Not applicable.

Background Art

[0003] Tumor Treating Fields (TTFields or TTF) are low - intensity (e.g., 1 - 3 V / cm) alternating electric fields within the intermediate frequency range (50 kHz to 1 MHz) that target solid tumors by disrupting mitosis. This non - invasive treatment targets solid tumors and is described, for example, in U.S. Pat. Nos. 7,016,725, 7,089,054, 7,333,852, 7,565,205, 8,244,345, 8,715,203, 8,764,675, 10,188,851, and 10,441,776. TTFields are typically delivered via two pairs of transducer arrays that generate fields perpendicular within the treated tumor, and the transducer arrays that make up each of these pairs are placed on opposite sides of the body part being treated. More specifically, for the OPTUNE® system, one pair of electrodes of the transducer array is placed on the left - right (LR) of the tumor and the other pair of electrodes is placed on the anterior - posterior (AP) of the tumor. TTFields are approved for the treatment of glioblastoma multiforme (GBM) and can be delivered, for example, via the OPTUNE® system (Novocure Limited, St. Helier, Jersey) that includes transducer arrays placed on a patient's shaved head.

[0004] Each transducer array used for TTField delivery in the OPTUNE® device comprises a set of non-conductive ceramic disc electrodes bonded to the patient's skin (but not limited to the patient's shaved head for GBM treatment) via a layer of conductive medical gel. To form the ceramic disc electrodes, a conductive layer is formed on the upper surface of the non-conductive ceramic material. The bottom surface of the non-conductive ceramic material is bonded to the conductive medical gel. The non-conductive ceramic material is a safety feature to ensure that DC signals are not unintentionally transmitted to the patient. By inserting the non-conductive ceramic material between the conductive layer and the conductive medical gel, the conventional system has been considered to ensure that the patient remains protected. The purpose of the medical gel is to deform to conform to the body's contours and provide good electrical contact between the array and the skin, so that the gel interface bridges the skin and reduces interference. The device is intended to be worn by the patient continuously for 2-4 days, then removed for hygienic care and reshaving (if necessary), after which a new set of arrays is reapplied. Therefore, the medical gel remains in substantially continuous contact with an area of ​​the patient's skin for 2 to 4 days at a time, and the area of ​​skin is only briefly exposed to the environment without being covered before the medical gel is applied again.

[0005] One method for applying TTField in different directions is to apply the field between a first set of electrodes for a certain period, then apply the field between a second set of electrodes for a certain period, and then repeat the cycle for a long duration (e.g., several days or several weeks).

[0006] To generate a TTField, an electric current is applied to each electrode of the transducer array. Applying current over a period of time can cause each electrode to warm up and eventually become hot, which may be uncomfortable or painful for the patient. Therefore, the amplitude of the alternating current delivered through the transducer array can be controlled so that the skin temperature (measured in the skin beneath the transducer array) does not exceed a safety threshold (e.g., 41 degrees Celsius). Temperature measurements in the patient's skin are obtained using temperature sensors (e.g., thermistors) placed beneath some of the disks in the transducer array. For example, each array may contain eight thermistors, with one thermistor placed beneath each disk in the array.

[0007] Each thermistor in an array is connected via long wires to an electronic device called a "cable box," where the temperature from all thermistors (e.g., 8 thermistors per 4 arrays) is measured and converted from analog to digital to a digital value for each thermistor. These measurements are then transmitted from the cable box to the electric field generator via additional wires that facilitate bidirectional digital serial communication between the cable box and the field generator. A controller within the field generator uses the temperature measurements to control the current that should be delivered through each pair of arrays to maintain the temperature in the patient's skin below, for example, 41 degrees Celsius. The current itself is delivered to each array via additional wires running from the field generator through the cable box to the arrays (i.e., one wire for each array). However, attaching the temperature sensor and transducer arrays to the patient is cumbersome due to the amount of wire. [Prior art documents] [Patent Documents]

[0008] [Patent Document 1] U.S. Patent No. 7,016,725 [Patent Document 2] U.S. Patent No. 7,089,054 [Patent Document 3] U.S. No. 7,333,852 [Patent Document 4] U.S. Patent No. 7,565,205 [Patent Document 5] U.S. Patent No. 8,244,345 [Patent Document 6] U.S. Patent No. 8,715,203 [Patent Document 7] U.S. Patent No. 8,764,675 [Patent Document 8] U.S. Patent No. 10,188,851 [Patent Document 9] U.S. Patent No. 10,441,776 [Overview of the Initiative] [Means for solving the problem]

[0009] In some embodiments, an apparatus for applying an electric field through a target area in a patient's body is described. The apparatus may comprise at least one transducer array, a sensor array, a circuit, and a controller. The at least one transducer array has a plurality of electrode elements configured to be placed on the patient's body, the electrode elements configured to provide a TTField via an AC waveform. The sensor array has a plurality of temperature sensors located in the vicinity of the plurality of electrode elements, with a plurality of first temperature sensors in the sensor array connected to a first conductor and a plurality of second temperature sensors connected to a second conductor. The circuit is configured to provide a known amount of electricity to a third temperature sensor via the first and second conductors, the third temperature sensor being located within the first plurality of first temperature sensors and a second plurality of second temperature sensors, and the circuit is configured to obtain a first electrical reading corresponding to a first temperature reading of the third temperature sensor. The controller adjusts the AC waveform based on the first temperature reading. [Brief explanation of the drawing]

[0010] [Figure 1]This is a block diagram of an exemplary system for measuring the temperature of a transducer array that applies TTField to a patient's body, as disclosed herein. [Figure 2] This is a schematic diagram of an exemplary hub for use in the system shown in Figure 1, as disclosed herein. [Figure 3] This is a schematic diagram of an exemplary distal circuit for use in the system shown in Figure 1, according to this disclosure. [Figure 4A] This is a schematic diagram of an exemplary embodiment of a sensor array for use in the system shown in Figure 1, according to the present disclosure. [Figure 4B] This is a schematic diagram of an exemplary embodiment of a sensor array for use in the system shown in Figure 1, according to the present disclosure. [Figure 4C] This is a schematic diagram of an exemplary embodiment of a sensor array for use in the system shown in Figure 1, according to the present disclosure. [Figure 5] This is a schematic diagram of another exemplary embodiment of a sensor array for use in the system shown in Figure 1, according to the present disclosure. [Modes for carrying out the invention]

[0011] Before describing in detail, by exemplary language and results, at least one embodiment of the concept of the present invention, it should be understood that the concept of the present invention is not limited in its application to the structural details and configurations described below. The language used herein is intended to be as broad as possible in scope and meaning, and the embodiments are illustrative and not exhaustive.

[0012] Unless otherwise required by context, singular terms shall include plural forms, and plural terms shall include singular forms.

[0013] All patents, published patent applications, and non-patent publications referred to in any part of this application are hereby expressly incorporated by reference in their entirety to the same extent as if each individual patent or document were specifically and individually indicated to be incorporated by reference. When used in accordance with this disclosure, the following terms shall be understood to have the following meanings unless otherwise indicated.

[0014] When used in conjunction with the term "comprising" in the claims and / or the specification, the use of the term "a" or "an" may mean "one", but is also consistent with the meanings of "one or more", "at least one", and "one or more". Accordingly, the terms "a", "an", and "the" include plural referents unless the context clearly indicates otherwise. Thus, for example, a reference to a "compound" may refer to one or more compounds. The term "plural" refers to "two or more".

[0015] The use of the term "at least one" will be understood to include not only one, but also any quantity of two or more. In addition, the use of the term "at least one of X, Y, and Z" will be understood to include X alone, Y alone, and Z alone, as well as any combination of X, Y, and Z. The use of ordinal terms (i.e., "first", "second", "third", "fourth", etc.) is for the sole purpose of distinguishing between two or more items and is not intended to imply any sequence or order or importance of one item with respect to another item, or any order of additional items.

[0016] The use of the term “or” in the claims is used to mean an inclusive “and / or” unless it is explicitly indicated that only alternatives are to be shown, or unless the alternatives are mutually exclusive. For example, the condition “A or B” is satisfied by any of the following: A is true (or exists) and B is false (or does not exist); A is false (does not exist) and B is true (or exists); and both A and B are true (or exist).

[0017] Where used herein, any reference to “one embodiment,” “embodiment,” “several embodiments,” “example,” “for example,” or “example” means that certain elements, features, structures, or characteristics described in relation to the embodiment are included in at least one embodiment.

[0018] Throughout this application, the term “approximately” is used to indicate that the value includes inherent variations in the error of the apparatus / device, the method used to determine the value, or variations that exist between the subjects of study.

[0019] As used herein and in the claims, the words “to have” (and any variation of “to have,” such as “to have” and “to have”), “to possess” (and any variation of “to possess,” such as “to possess” and “to possess”), “to include” (and any variation of “to include,” such as “to include” and “to include”), or “to contain” (and any variation of “to contain,” such as “to contain” and “to contain”) are inclusive or unrestricted and do not exclude any additional unlisted elements or method steps.

[0020] As used herein, the term “or any combination thereof” refers to all permutations and combinations of the items listed before the term. For example, “A, B, C, or any combination thereof” includes at least one of A, B, C, AB, AC, BC, or ABC, and is also intended to include BA, CA, CB, CBA, BCA, ACB, BAC, or CAB, where the order is useful in the particular context.

[0021] As used herein, the term “substantial” means that the event or situation described thereafter occurs completely, or occurs to a considerable degree or extent. For example, in relation to a particular event or situation, the term “substantial” means that the event or situation described thereafter occurs with a probability of at least 80%, or at least 85%, or at least 90%, or at least 95%. For example, the term “substantial” means that two items are 100% adjacent to each other, or that two items are very close to each other but not 100% adjacent, or that a portion of one of the two items is very close to the other but not 100% adjacent.

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

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

[0024] As discussed above, attaching temperature sensor and transducer arrays to patients is cumbersome due to the number of wires. Therefore, the inventors recognized the need for a new, improved array assembly that reduces the number of wires, thereby improving patient comfort and reducing costs. This disclosure is directed to such an assembly, as well as methods for producing and using it.

[0025] Now, turning to the concept of the present invention, a particular non-limiting embodiment thereof will be described, which includes an apparatus for applying an electric field through a target area in a patient's body. The apparatus may comprise at least one transducer array, a sensor array, a circuit, and a controller. The at least one transducer array has a plurality of electrode elements configured to be placed on the patient's body, the electrode elements configured to provide a TTField via an AC waveform. The sensor array has a plurality of temperature sensors located in the vicinity of the plurality of electrode elements, a plurality of first temperature sensors in the sensor array connected to a first conductor, and a plurality of second temperature sensors connected to a second conductor. The circuit is configured to provide a known amount of electricity to a third temperature sensor via the first and second conductors, the third temperature sensor being located within a plurality of first temperature sensors and a plurality of second temperature sensors, and the circuit is configured to obtain a first electrical reading corresponding to a first temperature reading of the third temperature sensor. The controller adjusts the AC waveform based on the first temperature reading.

[0026] Referring here to the drawings, particularly Figures 1 and 2, a block diagram of an exemplary embodiment of a system 10 having one or more circuits 12 is shown. The circuits 12 are described herein, for example, as one or more distal circuits 12 positioned very close to one or more transducer arrays 14 for acquiring one or more temperature readings from one or more temperature sensors 16. Each of the transducer arrays 14 includes one or more electrode elements 18. Alternative structures of the transducer arrays 14 may also be used, including, for example, transducer arrays using non-disk-shaped ceramic elements, and / or transducer arrays using non-ceramic dielectric material arranged on a plurality of flat conductors. An example of the latter includes polymer films arranged on pads on a printed circuit board or on flat metal pieces. Transducer arrays using uncoupled electrode elements may also be used. In this scenario, each element of the transducer array may be implemented using a region of conductive material configured to be positioned relative to the human body, without an insulating dielectric layer between the conductive element and the body. Examples of conductive materials include, but are not limited to, conductive films, conductive fabrics, and / or conductive foams. Other alternative structures for mounting the transducer array may also be used, insofar as (a) TTField can be delivered to the human body and (b) the improved connector design described herein is utilized and positioned at the location specified herein. Optionally, in any of the embodiments described herein, a layer of hydrogel may be placed between the transducer array and the human body.

[0027] One or more temperature sensors 16 are arranged to detect the temperature at the electrode element 18. In some embodiments, the temperature sensor 16 may be a thermistor, thermocouple, resistance temperature detector (RTD), integrated circuit temperature sensor such as Analog Devices AD590 and Texas Instruments LM135, and / or a combination thereof.

[0028] Each distal circuit 12 interfaces with one or more temperature sensors 16 incorporated into each transducer array 14 to obtain temperature readings from each of the one or more temperature sensors 16. The distal circuit 12 may then convert the temperature readings (e.g., from analog to digital), transfer the temperature readings, and / or transmit the temperature readings to the hub 20. The hub 20 may then transfer the temperature readings and / or transmit the temperature readings to the field generator 22 (e.g., via a serial communication link). In some embodiments, the field generator 22 may determine to adjust the current to the transducer array 14 based on the temperature readings.

[0029] In some embodiments, the conductor 30 may extend distally into the transducer array 14 beyond the distal circuit 12. Each temperature sensor 16 may be connected to at least two conductors 30 such that selective activation of at least two conductors 30 may activate the temperature sensor 16 to acquire one or more temperature readings (e.g., time-based selective activation).

[0030] In addition, wiring extending from the distal circuit 12 may include, but are not limited to, one or more conductors for common ground of one or more temperature sensors, and one or more conductors for TTField signals (i.e., AC current for electrode elements). In some embodiments, the distal circuit 12 may be implemented using a single-chip microcontroller or a programmable system on chip (PSoC) with an integrated analog front end and multiplexer. A part number suitable for this purpose is CY8C4124LQI-443, manufactured by Cypress Semiconductor Corp., which has its main business office in San Jose, California.

[0031] As those skilled in the art will understand, some embodiments may include one or more microcontrollers having an integrated and / or separate analog front-end and / or multiplexer. For example, the analog front-end and multiplexer may acquire temperature readings from one or more temperature sensors 16. These temperature readings may then be digitized and / or transmitted to the hub 20 (e.g., via a serial data link). In some embodiments, each distal circuit 12 may also include one or more through-conductors 34 (see Figure 3). One or more through-conductors 34 may be configured to route one or more TTField signals generated in the field generator 22 to the transducer array 14.

[0032] In some embodiments, each distal circuit 12 may be connected to the hub 20 via one or more cables 36. Conductors 34 in each cable 36 may run between the distal circuit 12 and the hub 20. For example, in Figure 3, four conductors 34 run between each distal circuit 12 and the hub 20, including one conductor 34 for power (Vcc), one conductor 34 for ground (GND), one conductor for serial data communication (DATA), and one conductor for the TTF signal.

[0033] Generally, the hub 20 may receive one or more temperature readings from each of the distal circuits 12 and transmit one or more temperature readings to the field generator 22. A wide variety of architectures may be used to receive and transmit one or more temperature readings. For example, Figure 2 shows a controller 40 configured to send a signal to a digital multiplexer (digital MUX) 42 instructing the digital multiplexer 42 to select one of the distal circuits 12 so that the hub 20 can receive digital data from the distal circuits 12 (e.g., the first distal circuit 12).

[0034] The controller 40 receives one or more temperature readings from the selected input of the distal circuit 12 and transmits one or more temperature readings to the field generator 22 via the transceiver 44. The controller 40 may then update the control signal to the digital multiplexer 42 so that the digital multiplexer 42 selects another distal circuit 12 (e.g., a second distal circuit 12). The controller 40 then receives one or more temperature readings from the input of the second distal circuit 12 and transmits one or more temperature readings to the field generator 22. A corresponding sequence may then be performed to obtain appropriate temperature readings (e.g., nine temperature readings) from each of the distal circuits 12. In some embodiments, the entire sequence, or part of the sequence, for obtaining one or more temperature readings from each of the distal circuits 12 may be repeated periodically (e.g., every 1 / 100 second, every second, every 10 seconds, or every 30 seconds, etc.) to update the one or more temperature readings provided to the field generator 22.

[0035] In some embodiments, the controller 40, digital multiplexer 42, and / or transceiver 44 may be integrated on a single chip. In some embodiments, the controller 40 and digital multiplexer 42 may be integrated into a circuit including a single chip, with a separate transceiver 44 used. For example, the controller 40 and digital multiplexer 42 may be implemented using Cypress CY8C4244LQI-443 manufactured by Cypress Semiconductor Corp., which has its main business office in San Jose, California, and the transceiver 44 may be implemented using Linear Technology LTC2856CMS8-2#PBF manufactured by Linear Technology Corp., which has its main business office in Milpitas, California. The controller 40 and / or digital multiplexer 42 may be implemented as a processor that runs software performing the functions described herein.

[0036] The hub 20 can communicate with the field generator 22 using any conventional communication technique (e.g., RS485). In some embodiments, the hub 20 may include one or more through conductors configured to directly pass one or more TTField signals from the field generator 22 to each of the transducer arrays 14. In some embodiments, the hub 20 can communicate with the field generator 22 via an eight-conductor spiral cable 50, optionally connected via a connector 21 (Figure 1). For example, the hub 20 can communicate with the field generator 22 via an eight-conductor spiral cable 25, where four wires (e.g., P1, P2, N1, N2) may provide TTField signals from each transducer array 14, one wire may provide ground (GND), one wire may provide voltage (Vcc) to the distal circuit 12, and two wires may provide communication (RS485A and RS485B). It should be understood that the use of the 8-conductor spiral cable 50 is configured to be backward compatible with previous versions of TTField delivery systems in the art, as will be understood by those skilled in the art.

[0037] The communication wire may be configured to perform data communication (i.e., about temperature data) between the distal circuit 12, the hub 20, and the field generator 22. In some embodiments, a single wire may be configured to perform communication in each direction. In some embodiments, the total number of wires between the hub 20 and the field generator 22 can be reduced by replacing multiple data communication wires with a single data wire that implements bidirectional communication (using a conventional single-wire communication protocol).

[0038] Figure 3 is a schematic diagram of an exemplary distal circuit 12 for interface the hub 20 to one or more transducer arrays 14. Each transducer array 14 may include one or more electrode elements 18 and one or more temperature sensors 16 (e.g., 16a-i in Figure 3) arranged to sense the temperature of one or more electrode elements 18. One or more temperature sensors 16 may include, but are not limited to, thermistors, thermocouples, RTDs, integrated circuit temperature sensors such as Analog Devices AD590 and Texas Instruments LM135, and / or combinations thereof. Any temperature sensor 16 known in the art may be used, provided that it is configured to provide accurate and / or precise temperature readings in accordance with this disclosure. In some embodiments, one or more temperature sensors 16 may be thermistors.

[0039] The distal circuit 12 may include a first multiplexer (MUX1) 60a and a second multiplexer (MUX2) 60b. Generally, the first multiplexer 60a drives a known amount of electricity (e.g., current) to one or more temperature sensors 16, and the second multiplexer 60b electrically connects one or more temperature sensors 16 to a reference point (e.g., GND).

[0040] The first multiplexer 60a includes an output 62a and one or more selectable inputs 64a. Each of the one or more selectable inputs 64a may be connected to two or more temperature sensors 16. Similarly, the second multiplexer 60b includes an output 62b and one or more selectable inputs 64b. Each of the one or more selectable inputs 64b may be connected to two or more temperature sensors 16. To this end, each temperature sensor 16 may be connected to at least two conductors 30. At least one terminal 64c may be connected to common ground. In some embodiments, the output 62a of the first multiplexer 60a may be supplied to the input 66 of an amplifier 68 (for example, an amplifier having a high input impedance, such as an operational amplifier configured as a voltage follower). The output 70 of the amplifier 68 may be supplied to the input 72 of an analog-to-digital converter (ADC) 74. The output 76 of the analog-to-digital converter is supplied to the input 78 of a controller 80. The controller 80 may include, but is not limited to, a circuit including a processor that executes computer executable instructions, such as software, in order to perform the functions described herein.

[0041] In some embodiments, the controller 80 may be configured to coordinate the operation of one or more of the components within the dashed line 82. The controller 80 may be configured to send one or more commands to the first multiplexer 60a and the second multiplexer 60b to select two or more conductors 30 to communicate with one of the temperature sensors 16 in order to obtain a temperature reading from the temperature sensors 16. In some embodiments, the first multiplexer 60a and the second multiplexer 60b are configured to provide an open circuit with respect to the unselected conductors 30 so that only a specific one of the temperature sensors 16 is read at any particular moment.

[0042] In some embodiments, temperature readings can be obtained by routing a known amount of electricity, e.g., current, through at least two conductors 30 to a temperature sensor 16 (e.g., a thermistor) and measuring the electrical reading, e.g., voltage, that appears across the temperature sensor 16. For example, a programmable current source 84 may be configured to generate a known current (e.g., 150 μA) through at least two conductors 30. The first multiplexer 60a may be bidirectional so that the known current can be routed to the temperature sensor 16 through the conductors 30 selected by the first multiplexer 60a.

[0043] Referring to Figures 3 and 4A, temperature readings obtained from the temperature sensor 16 in the sensor array 90a can be obtained using the selective activation of at least two conductors 30. For example, several first temperature sensors 16a, 16d, and 16g of the sensor array 90a are connected to the first conductor 30a. For example, several second temperature sensors 16a, 16b, and 16c of the sensor array 90a are connected to the second conductor 30d. The controller 80 sends one or more commands to the first multiplexer 60a and the second multiplexer 60b to select at least two conductors 30a and 30d to communicate with the third temperature sensor 16a in the sensor array 90a, and configures the current source 84 to generate a known current through the two conductors 30a and 30d. In this example, the third temperature sensor 16a is located within a plurality of first temperature sensors (16a, 16d, and 16g) and also within a plurality of second temperature sensors (16a, 16b, and 16c).

[0044] A known current from the current source 84 is configured to flow through the first multiplexer 60a to the third temperature sensor 16a via two conductors 30a and 30b connected to the third temperature sensor 16a, resulting in a voltage appearing at the output 62a of the first multiplexer 60a across the third temperature sensor 16a. In some embodiments, a known current from the current source 84 is configured to flow through the first multiplexer 60a to the third temperature sensor 16a via two conductors 30a and 30b connected to the third temperature sensor 16a, resulting in a voltage appearing across the third temperature sensor 16a and the output 62a of the first multiplexer 60a. The input 66 of the amplifier 68 receives the voltage appearing across the third temperature sensor 16a, the amplifier 68 amplifies the voltage, and then provides the amplified voltage to the input 72 of the analog-to-digital converter 74. The controller 80 instructs the analog-to-digital converter 74 to digitize the resulting voltage. The controller 80 acquires the voltage reading resulting from the digitization from the analog-to-digital converter 74, temporarily stores the resulting voltage reading (corresponding to the third temperature sensor 16a) in a buffer, and uses the resulting voltage reading to determine the temperature reading based on the resulting voltage reading. The resulting voltage reading may be referred to herein as the first electrical reading. This procedure may be repeated sequentially for each of the temperature sensors 16 having conductors 30 (i.e., 30a-f) in the sensor array 90a. For example, to acquire a reading from temperature sensor 16b, the controller 80 sends one or more commands to the first multiplexer 60a and the second multiplexer 60b to select at least two conductors 30b and 30d, both of which communicate with temperature sensor 16b, and configures the current source 84 to generate a known current in at least two conductors 30b and 30d.A known current from the current source 84 is configured to flow through the first multiplexer 60a, through conductor 30b to the temperature sensor 16b, and through conductor 30d to the second multiplexer 60b, resulting in a voltage appearing at the output 62a of the first multiplexer 60a across the temperature sensor 16b. The input 66 of the amplifier 68 receives the voltage appearing across the temperature sensor 16b, and the amplifier 68 amplifies the voltage and then provides the amplified voltage to the input 72 of the analog-to-digital converter 74. The controller 80 instructs the analog-to-digital converter 74 to digitize the resulting voltage. The controller 80 obtains the resulting digitized voltage reading from the analog-to-digital converter 74 and temporarily stores the digitized resulting voltage reading (corresponding to the third temperature sensor 16a) in a buffer, and the digitized resulting voltage reading is used to determine the temperature reading based on the digitized resulting voltage reading. The resulting digitized voltage reading from the temperature sensor 16b may be referred to herein as the second electrical reading. Similarly, to obtain a reading from the temperature sensor 16h, the controller 80 sends one or more commands to the first multiplexer 60a and the second multiplexer 60b to select at least two conductors 30b and 30f to communicate with the temperature sensor 16h, and configures the current source 84 to generate a known current. The known current from the current source 84 is configured to flow through the first multiplexer 60a, through conductor 30b to the temperature sensor 16h, and through conductor 30f to the second multiplexer 60b, resulting in a voltage that appears at the output 62a of the multiplexer 60a across the temperature sensor 16h. The controller 80 may pass the first temperature reading and / or the second temperature reading to the controller 40 in the hub 20, and the controller 40 may communicate with the field generator 22 to adjust the AC waveform based on the first temperature reading and / or the second temperature reading.

[0045] It should be understood that additional conductors 30 may be used to increase the number of temperature sensors 16 in the sensor array 90. For example, Figure 4B shows another exemplary embodiment of a sensor array 90b having 13 temperature sensors 16a to 16m connected to conductors 30a to 30h. Selective activation of at least two predetermined conductors 30 may result in a voltage appearing across at least one temperature sensor 16 connected to at least two conductors 30, resulting in a temperature reading as described herein. Figure 4C shows another exemplary embodiment of a sensor array 90c having 20 temperature sensors 16a to 16t connected to conductors 30a to 30i. Selective activation of at least two conductors 30 may result in a voltage appearing across the temperature sensors 16 connected to at least two conductors 30, resulting in a temperature reading as described herein.

[0046] Figure 5 shows another exemplary embodiment of a sensor array 90d that includes a reduced number of conductors 30 (30a-d) compared to the embodiments of Figures 4A-4C, including a plurality of electronic switches 92 (92a-h) such as diodes configured to provide selective activation of one temperature sensor 16 (Figure 5 shows 16a-16h) when two or more temperature sensors 16 are connected to two conductors 30. In one embodiment, selection of a temperature sensor 16 can be achieved by providing a voltage of a specific polarity across two conductors 30. Generally, a specific temperature sensor 16 can be activated by providing positive or negative polarity to a combination of conductors 30. For example, two temperature sensors 16g and 16h are circuit-connected to two conductors 30b and 30d as well as two electronic switches 92g and 92h. Electronic switch 92g is in series with temperature sensor 16g, and electronic switch 92h is in series with temperature sensor 16h. The electronic switch 92g is configured to conduct based on negative polarity, and the electronic switch 92h is configured to conduct based on positive polarity. By applying positive polarity across conductors 30b and 30d, the temperature sensor 16h is activated (and the temperature sensor 16g is not activated), and a temperature reading can be provided. By applying negative polarity across the same conductors 30b and 30d, the temperature sensor 16g is activated (and the temperature sensor 16h is not activated), and a temperature reading can be provided.

[0047] Referring to Figure 3, in some embodiments, a conventional voltage divider technique may be used to interface with one or more temperature sensors 16. In some embodiments, additional readings may be acquired and used for self-calibration to improve the accuracy and / or precision of the temperature readings obtained from one or more temperature sensors 16. For example, in Figure 3, at least one input 64c of the first multiplexer 60a is connected to ground, and at least one input 64d of the first multiplexer 60a is connected to a high-precision resistor 100. The controller 80 may temporarily store the digitized readings from the high-precision resistor 100 and the ground input 64c in any memory configured to buffer and / or store data. These additional readings may ultimately be used to calibrate the readings obtained from one or more temperature sensors 16. In some embodiments, such calibration may be performed via the controller 80. In some embodiments, the calibration may be performed before transmitting the digital data corresponding to the temperature readings. In some embodiments, calibration may be performed in a downstream processor (e.g., a controller 40 in a hub 20) such that digital data corresponding to a high-precision resistor 100 (and optionally a ground input 64) can be transmitted to the downstream processor in addition to any uncalibrated temperature readings obtained from one or more temperature sensors 16.

[0048] In some embodiments, calibration using a high-precision resistor 100 may involve comparing the actual voltage measured across the high-precision resistor 100 with an expected voltage based on Ohm's law, a known value of the high-precision resistor 100, and an expected value of the current generated by the current source 84. The deviation between the actually measured voltage and the expected voltage may be used to determine subsequent measurements from one or more temperature sensors 16 (e.g., as a multiplier).

[0049] In some embodiments, the controller 80 in the distal circuit 12 may be configured to communicate with the hub 20 via a universal asynchronous receiver-transmitter (UART) 102 and transmit temperature readings obtained from one or more temperature sensors 16 to the hub 20. In some embodiments, the controller 80 may be a processor programmed to operate autonomously and configured to automatically collect temperature readings from each of the one or more temperature sensors 16, store the results in a buffer as described above, and then transmit the contents of the buffer (i.e., the readings from each of the temperature sensors 16, and optionally any additional readings as described herein) to the hub 20.

[0050] In some embodiments, the controller 80 may be a processor programmed to act as a slave to a master controller located within the hub 20. For example, the controller 80 may start in a quiescent state in which it independently monitors incoming commands from the master controller arriving via the UART 102. Examples of commands that may arrive from the master controller include, but are not limited to, a “Sample Acquisition” command and a “Data Transmission” command. When the controller 80 recognizes that a “Sample Acquisition” command has arrived, the controller 80 may initiate a method described herein to acquire one or more temperature readings from one or more temperature sensors 16 and may be configured to store the results in any memory configured to store buffers and / or data. In another example, the controller 80 may recognize a “Data Transmission” command and perform a method to send previously acquired temperature readings from the buffers and / or memory to the hub 20 via the UART 102.

[0051] In some embodiments, temperature readings can be synchronized. For example, a controller 40 in the hub 20 may send “sample acquisition” commands simultaneously or in rapid succession to one or more controllers 80 in the distal circuit 12 so that temperature readings acquired from each of the transducer arrays 14 can be acquired simultaneously or nearly simultaneously. In some embodiments, temperature readings can be collected by the hub 20 in one or more batches of each controller 80.

[0052] Most systems using TTField to treat tumors periodically (e.g., every second) switch the direction of the field applied to the tumor. To minimize noise in temperature measurements, short time gaps may be introduced in which the field is not applied in either direction, and temperature measurements can be taken during these time gaps. In some embodiments, a controller 40 located within the hub 20 may synchronize the timing of “sampling” commands to all controllers 80 so that each of the distal circuits 12 can acquire a temperature reading during the time gap. Temperature readings acquired simultaneously from each transducer array 14 can minimize the duration of the time gap. For example, if system 10 requires 100 microseconds to acquire a single measurement, acquiring 36 measurements in a sequence (i.e., 4 distal circuits × 9 temperature sensors 16 in each distal circuit 12, etc.) may take 3.6 milliseconds. In contrast, when each of the four distal circuits 12 operates in parallel, each distal circuit 12 can acquire 9 samples in 900 microseconds, so that 36 samples can be acquired in 900 microseconds. It should be noted that the "transmit data" command may be noise-insensitive and therefore less time-constrained, so that it can be executed while the field remains on.

[0053] In some embodiments, some or all of the following components, namely the first multiplexer 60a, the second multiplexer 60b, the amplifier 68, the analog-to-digital converter 74, the controller 80, the UART 102, and the current source 84, can be implemented by a single integrated circuit. An example of a single integrated circuit containing all of these functional blocks is the Cypress CY8C4124LQI-443T Programmable System-on-Chip (PSoC), manufactured by Cypress Semiconductor Corp., which has its main business office in San Jose, California.

[0054] Embodiments illustrated under any heading or in any part of this disclosure may be combined with embodiments illustrated under the same or any other heading or other part of this disclosure. Any combination of all possible modifications of the elements described herein is incorporated herein unless otherwise indicated herein or unless explicitly stated otherwise in the context.

[0055] The present invention includes the following other exemplary embodiments:

[0056] Exemplary Embodiment 1. A device for applying an electric field through a target area in a patient's body, wherein the device comprises, A transducer array having a plurality of electrode elements configured to be placed on a patient's body, wherein the electrode elements are configured to provide a TTField via an AC waveform, A sensor array having multiple temperature sensors arranged in the vicinity of multiple electrode elements, wherein multiple first temperature sensors of the sensor array are connected to a first conductor, and multiple second temperature sensors are connected to a second conductor, A circuit configured to supply a known amount of electricity to a third temperature sensor via a first conductor and a second conductor, wherein the third temperature sensor is located within a first plurality of first temperature sensors and a second plurality of second temperature sensors, and the circuit is configured to acquire a first electrical reading corresponding to a first temperature reading of the third temperature sensor. A controller that adjusts the AC waveform based on the first temperature reading, A device equipped with the following features.

[0057] Exemplary Embodiment 2. The circuit is, A current source that provides a known amount of electricity, A first multiplexer having an input and an output, wherein the first multiplexer is connected to a current source, A second multiplexer having inputs and outputs, wherein the second multiplexer is connected to a reference point, A controller configured to send at least one command to a first multiplexer to select a first conductor and at least one command to a second multiplexer to select a second conductor, The apparatus of exemplary embodiment 1 further comprises the following.

[0058] Exemplary Embodiment 3: The apparatus of Exemplary Embodiment 2, wherein the controller is configured to communicate with a current source and instruct the current source to generate a known amount of electricity in a first conductor and a second conductor.

[0059] Exemplary Embodiment 4. Apparatus of Exemplary Embodiment 2, wherein the first electrical reading is acquired at the output of the first multiplexer.

[0060] Exemplary Embodiment 5. The apparatus of Exemplary Embodiment 4, further comprising an analog-to-digital converter configured to acquire a first electrical reading and provide a digitized resulting reading corresponding to the first temperature reading of a third temperature sensor.

[0061] Exemplary Embodiment 6. The apparatus of Exemplary Embodiment 5, wherein the circuit further comprises a buffer configured to store the readings resulting from the digitization of a third temperature sensor.

[0062] Exemplary Embodiment 7: The apparatus of Exemplary Embodiment 5, wherein the circuit further comprises an amplifier configured to receive a first electrical reading and provide an amplified voltage to an analog-to-digital converter.

[0063] Exemplary Embodiment 8. Any one of the Exemplary Embodiments 1 to 7, wherein a known amount of electricity is a known current, and the sensor array includes at least 12 temperature sensors, each temperature sensor being connected to at least two conductors such that providing a known current to at least two conductors connected to the temperature sensors provides a voltage across the temperature sensors.

[0064] Exemplary Embodiment 9. Any one of Exemplary Embodiments 1 to 8, wherein a known amount of electricity is a known current, and the sensor array includes at least 13 temperature sensors, each temperature sensor being connected to two conductors such that providing a current to the two conductors connected to the temperature sensors provides a voltage across the temperature sensors.

[0065] Exemplary Embodiment 10. An apparatus of any one of the exemplary embodiments 1 to 9, wherein the sensor array comprises at least 24 temperature sensors, and each temperature sensor is connected to two conductors such that providing a known amount of electricity to two conductors connected to the temperature sensors provides an electrical reading across the temperature sensors.

[0066] Exemplary Embodiment 11. An apparatus from any one of the exemplary embodiments 1 to 10, wherein the sensor array includes a plurality of electronic switches configured to provide selective activation of a third temperature sensor.

[0067] Exemplary Embodiment 12. The apparatus of Exemplary Embodiment 11, wherein a first electronic switch is arranged in series with a third temperature sensor, and the first electronic switch is configured to conduct when a first predetermined polarity is arranged across the first electronic switch.

[0068] Exemplary Embodiment 13. The apparatus of Exemplary Embodiment 12, wherein a second electronic switch is arranged in series with a fourth temperature sensor such that a negative polarity across a first conductor results in a voltage across a fourth temperature sensor, and the second electronic switch is configured to conduct when a second predetermined polarity is arranged across the second electronic switch.

[0069] Exemplary Embodiment 14. A device for applying an electric field through a target area in a patient's body, wherein the device comprises, A transducer array having a plurality of electrode elements configured to be placed on a patient's body, wherein the electrode elements are configured to provide a TTField via an AC waveform, A sensor array having a first temperature sensor and a second temperature sensor, wherein the first temperature sensor of the sensor array is connected to a first conductor and a second conductor, and the second temperature sensor is connected to a first conductor and a third conductor, A first known amount of electricity is provided through the first conductor and the second conductor to activate the first temperature sensor, and a second known amount of electricity is provided through the first conductor and the third conductor to activate the second temperature sensor. Obtain a first electrical reading induced by a first known amount of electricity, and a second electrical reading induced by a second known amount of electricity. A first temperature reading is determined based on the first electrical reading, and a second temperature reading is determined based on the second electrical reading. A controller configured in such a way Equipped with, An apparatus in which an AC waveform is adjusted based on a first temperature reading and a second temperature reading.

[0070] Exemplary Embodiment 15. The apparatus of Exemplary Embodiment 14, wherein the sensor array further comprises a first electronic switch in a circuit having a first temperature sensor and a second electronic switch in a circuit having a second temperature sensor.

[0071] Exemplary Embodiment 16. The apparatus of Exemplary Embodiment 15, wherein the controller is further configured to provide selective activation of a first electronic switch or a second electronic switch.

[0072] Exemplary Embodiment 17. The apparatus of Exemplary Embodiment 16, wherein the first electronic switch is arranged in series with the first temperature sensor.

[0073] Exemplary Embodiment 18. The apparatus of Exemplary Embodiment 16, wherein a second electronic switch is arranged in series with a second temperature sensor.

[0074] Exemplary Embodiment 19. A step of providing a first known amount of electricity through a first conductor and a second conductor to activate a first temperature sensor of a sensor array, wherein the sensor array is positioned in close proximity to a transducer array having a plurality of electrode elements configured to be placed on a patient's body, and the electrode elements are configured to provide a TTField via an AC waveform. A step of obtaining a first temperature reading induced by the activation of a first temperature sensor, The steps include providing a second known amount of electricity through the first conductor and the third conductor in order to activate the second temperature sensor, A step of obtaining a second temperature reading induced by the activation of a second temperature sensor, A step of adjusting the AC waveform based on at least one of a first temperature reading and a second temperature reading. A method that includes this.

[0075] Exemplary Embodiment 20: The method of Exemplary Embodiment 19, wherein the step of adjusting the AC waveform is based on a second temperature reading.

[0076] From the above description, it is clear that the concept of the invention disclosed and claimed herein is not only unique to the present invention but is also well suited to accomplishing its purpose and achieving the advantages described herein. While exemplary embodiments of the concept of the present invention have been described for the purposes of this disclosure, it will be understood that many modifications can be made which are readily suggested to those skilled in the art and achieved within the gist of the concept of the invention disclosed and claimed herein. [Explanation of symbols]

[0077] 10 Systems 12 circuits 14 transducer arrays 16 Temperature Sensor 16a First temperature sensor, second temperature sensor, third temperature sensor 16a~16m Temperature Sensor 16a~16t Temperature Sensor 16b Temperature sensor, second temperature sensor 16°C temperature sensor, second temperature sensor 16d First temperature sensor 16g First temperature sensor 16h temperature sensor 18 Electrode elements 20 Hubs 21 Connectors 22 Field generator 25 8-conductor spiral cable 30 Conductors 30a First conductor, conductor 30a~30h Conductor 30a~30i Conductors 30d Second conductor, conductor 30f conductor 34 Through conductor 36 Cables 40 controllers 42 Digital multiplexer (digital MUX), digital multiplexer 44 transceivers 50 8-conductor spiral cable 60a First multiplexer (MUX1), First multiplexer 60b Second multiplexer (MUX2), second multiplexer 62a output 62b output 64a Input 64b Input 64c terminal, input, ground input 64d input 66 inputs 68 Amplifier 70 Output 72 inputs 74 Analog-to-digital converter (ADC), Analog-to-digital converter 80 Controllers 82 Dashed line 84 Programmable current source, current source 90a Sensor Array 92 Electronic switches 92a~h Electronic Switches 100 precision resistors 102 General-purpose asynchronous transceiver (UART), UART

Claims

1. A device for applying an electric field through a target region within a patient's body, wherein the device is A transducer array having a plurality of electrode elements configured to be placed on the patient's body, wherein the electrode elements are configured to provide a TTField via an AC waveform, A sensor array having a plurality of temperature sensors arranged in the vicinity of the plurality of electrode elements, wherein a plurality of first temperature sensors of the sensor array are connected to a first conductor, and a plurality of second temperature sensors are connected to a second conductor, A circuit configured to supply a known amount of electricity to a third temperature sensor via the first conductor and the second conductor, wherein the third temperature sensor is located within the plurality of first temperature sensors and within the plurality of second temperature sensors, and the circuit is configured to acquire a first electrical reading corresponding to a first temperature reading of the third temperature sensor. A controller that adjusts the AC waveform based on the first temperature reading, A device equipped with the following features.

2. The aforementioned circuit, A current source that provides the aforementioned known amount of electricity, A first multiplexer having an input and an output, wherein the first multiplexer is connected to the current source, A second multiplexer having an input and an output, wherein the second multiplexer is connected to a reference point, A controller configured to send at least one command to the first multiplexer to select the first conductor and at least one command to the second multiplexer to select the second conductor, The apparatus according to claim 1, further comprising:

3. The apparatus according to claim 2, wherein the controller is configured to communicate with the current source and instruct the current source to generate the known amount of electricity in the first conductor and the second conductor.

4. The apparatus according to claim 2, wherein the first electrical reading is obtained at the output of the first multiplexer.

5. The apparatus according to claim 4, further comprising an analog-to-digital converter configured to acquire the first electrical reading and provide a digitized resulting reading corresponding to the first temperature reading of the third temperature sensor.

6. The apparatus according to claim 5, wherein the circuit further comprises a buffer configured to store the digitized readings of the third temperature sensor.

7. The apparatus according to claim 5, wherein the circuit further comprises an amplifier configured to receive the first electrical reading and provide an amplified voltage to the analog-to-digital converter.

8. The apparatus according to any one of claims 1 to 7, wherein the known amount of electricity is a known current, and the sensor array comprises at least 12 temperature sensors, and each temperature sensor is connected to at least two conductors such that providing the known current to the temperature sensors provides a voltage across the temperature sensors.

9. The apparatus according to any one of claims 1 to 8, wherein the known amount of electricity is a known current, and the sensor array includes at least 13 temperature sensors, each temperature sensor being connected to the two conductors such that providing a current to the two conductors connected to the temperature sensors provides a voltage across the temperature sensors.

10. The apparatus according to any one of claims 1 to 8, wherein the sensor array comprises at least 24 temperature sensors, and each temperature sensor is connected to the two conductors such that providing the known amount of electricity to the two conductors connected to the temperature sensors provides an electrical reading across the temperature sensors.

11. The apparatus according to any one of claims 1 to 8, wherein the sensor array includes a plurality of electronic switches configured to provide selective activation of the third temperature sensor.

12. The apparatus according to claim 11, wherein a first electronic switch is arranged in series with the third temperature sensor, and the first electronic switch is configured to conduct when a first predetermined polarity is arranged across the first electronic switch.

13. The apparatus according to claim 12, wherein a second electronic switch is arranged in series with the fourth temperature sensor such that a negative polarity across the first conductor results in a voltage across the fourth temperature sensor, and the second electronic switch is configured to conduct when a second predetermined polarity is arranged across the second electronic switch.

14. A device for applying an electric field through a target region within a patient's body, wherein the device is A transducer array having a plurality of electrode elements configured to be placed on the patient's body, wherein the electrode elements are configured to provide a TTField via an AC waveform, A sensor array having a first temperature sensor and a second temperature sensor, wherein the first temperature sensor of the sensor array is connected to a first conductor and a second conductor, and the second temperature sensor is connected to the first conductor and a third conductor, A first known amount of electricity is provided through the first conductor and the second conductor for activating the first temperature sensor, and a second known amount of electricity is provided through the first conductor and the third conductor for activating the second temperature sensor. A first electrical reading induced by the first known amount of electricity and a second electrical reading induced by the second known amount of electricity are obtained. A first temperature reading is determined based on the first electrical reading, and a second temperature reading is determined based on the second electrical reading. A controller configured in such a way Equipped with, An apparatus in which the AC waveform is adjusted based on the first temperature reading and the second temperature reading.

15. The apparatus according to claim 14, wherein the sensor array further comprises a first electronic switch in a circuit having the first temperature sensor and a second electronic switch in a circuit having the second temperature sensor.

16. The apparatus according to claim 15, wherein the controller is further configured to provide selective activation of the first electronic switch or the second electronic switch.

17. The apparatus according to claim 16, wherein the first electronic switch is arranged in series with the first temperature sensor.

18. The apparatus according to claim 16, wherein the second electronic switch is arranged in series with the second temperature sensor.

19. A step of providing a first known amount of electricity through a first conductor and a second conductor to activate a first temperature sensor of a sensor array, wherein the sensor array is positioned in close proximity to a transducer array having a plurality of electrode elements configured to be placed on a patient's body, and the electrode elements are configured to provide a TTField via an AC waveform. The steps include obtaining a first temperature reading induced by the activation of the first temperature sensor, The steps include providing a second known amount of electricity through the first conductor and the third conductor in order to activate the second temperature sensor, The steps include obtaining a second temperature reading induced by the activation of the second temperature sensor, The steps of adjusting the AC waveform based on at least one of the first temperature reading and the second temperature reading, A method that includes this.

20. The method according to claim 19, wherein the step of adjusting the AC waveform is based on the second temperature reading.

Images