# US 12,502,548 B2 · Reducing electrosensation whilst treating a subject using alternating electric fields by using larger cathodes and smaller anodes > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,502,548 B2 - Document ID: US12502548B2 - Status: Granted - Kind: B2 - Application number: 18/089,798 - Filed: 2022-12-28 - Published: 2023-06-29 - Granted: 2025-12-23 - Earliest claimed: 2021-12-29 - Assignees: Novocure GmbH - Applicants: Novocure GmbH - Inventors: Kristen W. Carlson - Web page: https://patentgrep.com/patent/US12502548B2 ## CPC - A61N 1/40: Applying electric fields by inductive or capacitive coupling (microwave apparatus A61N5/00); {Applying radio-frequency signals} - A61N 1/0476: {Array electrodes (including any electrode arrangement with more than one electrode for at least one of the polarities)} - A61N 1/36002: {Cancer treatment, e.g. tumour} - A61N 1/3616: {Voltage density or current density} - A61N 1/3615: {Intensity} - A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B) ## Abstract When treating a subject using alternating electric fields (e.g., using TTFields to treat a tumor), some subjects experience an electrosensation effect. This electrosensation can be reduced or eliminated by applying a plurality of electrical pulses between two sets of electrode elements positioned on opposite sides of the target region. During the pulses, one set of electrode elements operate as the anode and the other set of electrode elements operate as the cathode. Electrosensation is reduced or eliminated because the collective area of the cathode is at least twice as large as the anode. An electrical signal with the opposite polarity is also applied to charge-balance the plurality of electrical pulses. The plurality of electrical pulses has an average amplitude that is at least twice the average amplitude of the charge-balancing signal. ## Claims ### Claim 1 A method of treating a target region of a subject's body with an electric field, the method comprising: applying a plurality of electrical pulses between at least one first electrode element and at least one second electrode element, wherein the at least one first electrode element and the at least one second electrode element are positioned on opposite sides of the target region, wherein the at least one first electrode element has a first collective area, wherein the at least one second electrode element has a second collective area that is at least twice as large as the first collective area, and wherein the plurality of electrical pulses has a polarity such that the at least one first electrode element operates as an anode and the at least one second electrode element operates as a cathode; and applying an electrical signal between the at least one first electrode element and the at least one second electrode element, wherein the electrical signal has a polarity such that the at least one first electrode element operates as a cathode and the at least one second electrode element operates as an anode, wherein the electrical signal charge-balances the plurality of electrical pulses, and wherein the electrical signal has an average amplitude, wherein the plurality of electrical pulses has an average amplitude that is at least twice the average amplitude of the electrical signal, wherein the plurality of electrical pulses has a pulse repetition rate between 50,000 and 1,000,000 pulses per second, and wherein the plurality of electrical pulses has a waveform that collectively resembles (i) a sequence of rectangular pulses with a 50% duty cycle, (ii) a rectified sinusoid, or (iii) an offset sinusoid. ### Claim 2 (depends on 1) The method of claim 1, wherein the plurality of electrical pulses comprises at least 1000 groups of electrical pulses, with each group including at least 1000 electrical pulses, with breaks having a duration of at least 10 ms disposed between adjacent groups, and wherein the electrical signal is applied during the breaks. ### Claim 3 (depends on 2) The method of claim 2, wherein the electrical signal is not applied during intervals of time that lie between adjacent pulses within a given group of electrical pulses. ### Claim 4 (depends on 2) The method of claim 2, wherein the electrical signal is also applied during intervals of time that lie between adjacent pulses within a given group of electrical pulses. ### Claim 5 (depends on 1) The method of claim 1, wherein the steps of (a) applying the plurality of electrical pulses and (b) applying the electrical signal are repeated in an alternating sequence at least 10,000 times. ### Claim 6 (depends on 5) The method of claim 5, wherein the plurality of electrical pulses has an average amplitude that is at least four times the average amplitude of the electrical signal, and wherein the second collective area is at least four times as large as the first collective area. ### Claim 7 (depends on 1) The method of claim 1, wherein the plurality of electrical pulses has an average amplitude that is at least four times the average amplitude of the electrical signal, and wherein the second collective area is at least four times as large as the first collective area. ### Claim 8 (depends on 1) The method of claim 1, wherein the plurality of electrical pulses comprises a plurality of rectangular pulses with a 50% duty cycle. ### Claim 9 (depends on 1) The method of claim 1, wherein the step of applying the plurality of electrical pulses between the at least one first electrode element and the at least one second electrode element induces an electric field in the target region that provides an anti-tumor effect. ### Claim 10 (depends on 1) The method of claim 1, wherein the step of applying the plurality of electrical pulses between the at least one first electrode element and the at least one second electrode element induces an electric field in the target region that increases the permeability of the subject's blood-brain-barrier. ### Claim 11 (depends on 1) The method of claim 1, wherein the at least one first electrode element comprises a first subset of a first array of electrode elements, wherein the at least one second electrode element comprises a second subset of a second array of electrode elements, and wherein the second subset contains at least twice as many electrode elements as the first subset. ### Claim 12 (depends on 1) The method of claim 1, wherein the plurality of electrical pulses has a waveform that collectively resembles a rectified sinusoid. ### Claim 13 (depends on 1) The method of claim 1, wherein the plurality of electrical pulses has a waveform that collectively resembles an offset sinusoid. ### Claim 14 An apparatus for treating a target region of a subject's body with an electric field, the apparatus comprising: a signal generator configured to output a plurality of electrical pulses between at least one first electrode element and at least one second electrode element, wherein the plurality of electrical pulses has a polarity such that the at least one first electrode element operates as an anode and the at least one second electrode element operates as a cathode, wherein the signal generator is further configured to output an electrical signal between the at least one first electrode element and the at least one second electrode element, the electrical signal having a polarity such that the at least one first electrode element operates as a cathode and the at least one second electrode element operates as an anode, wherein the electrical signal charge-balances the plurality of electrical pulses, and wherein the electrical signal has an average amplitude, and wherein the plurality of electrical pulses has an average amplitude that is at least twice the average amplitude of the electrical signal, wherein the plurality of electrical pulses has a pulse repetition rate between 50,000 and 1,000,000 pulses per second, and wherein the plurality of electrical pulses has a waveform that collectively resembles (i) a sequence of rectangular pulses with a 50% duty cycle, (ii) a rectified sinusoid, or (iii) an offset sinusoid. ### Claim 15 (depends on 14) The apparatus of claim 14, further comprising the at least one first electrode element and the at least one second electrode element, wherein the at least one first electrode element and the at least one second electrode element are configured for positioning on or in the subject's body on opposite sides of the target region, wherein the at least one first electrode element has a first collective area, and wherein the at least one second electrode element has a second collective area that is at least twice as large as the first collective area. ### Claim 16 (depends on 15) The apparatus of claim 15, wherein the plurality of electrical pulses has an average amplitude that is at least four times the average amplitude of the electrical signal, and wherein the second collective area is at least four times as large as the first collective area. ### Claim 17 (depends on 16) The apparatus of claim 16, wherein the plurality of electrical pulses comprises at least 1000 groups of electrical pulses, with each group including at least 1000 electrical pulses, with breaks having a duration of at least 10 ms disposed between adjacent groups, and wherein the signal generator is configured to output the electrical signal during the breaks. ### Claim 18 (depends on 17) The apparatus of claim 17, wherein the signal generator is configured not to output the electrical signal during intervals of time that lie between adjacent pulses within a given group of electrical pulses. ### Claim 19 (depends on 17) The apparatus of claim 17, wherein the signal generator is configured to also output the electrical signal during intervals of time that lie between adjacent pulses within a given group of electrical pulses. ### Claim 20 (depends on 14) The apparatus of claim 14, wherein the plurality of electrical pulses comprises a plurality of rectangular pulses with a 50% duty cycle. ### Claim 21 (depends on 14) The apparatus of claim 14, wherein the at least one first electrode element comprises a first subset of a first array of electrode elements, wherein the at least one second electrode element comprises a second subset of a second array of electrode elements, and wherein the second subset contains at least twice as many electrode elements as the first subset. ### Claim 22 (depends on 14) The apparatus of claim 14, wherein the plurality of electrical pulses has a waveform that collectively resembles a rectified sinusoid. ### Claim 23 (depends on 14) The apparatus of claim 14, wherein the plurality of electrical pulses has a waveform that collectively resembles an offset sinusoid.