Multi-channel device for directional shaping of electric fields such as tumor treatment fields (TT fields)

Abstract

The path of the alternating electric field through the body part can be controlled by providing at least eight electrically isolated signal generators, each configured to apply an electric signal between a respective electrode element on one side of the target region and a respective electrode element on the opposite side of the target region. This replaces the single wide cross-sectional electric field of the prior art with eight independently controllable electric fields, each having a relatively narrow cross-section. These relatively narrow cross-sectional fields can be used alone or in combination to improve the targeting of the electric field, which in turn can increase the field strength within the target region. Optionally, the activation of these relatively narrow cross-sectional fields can be shifted in time to achieve overall induction of the electric field.

Description

[Technical Field]

[0001] [CROSS-REFERENCE TO RELATED APPLICATIONS] This application claims the benefit of U.S. Provisional Application No. 63 / 435,370, filed December 27, 2022, which is incorporated herein by reference in its entirety. [Background technology]

[0002] Tumor treating field (TT field) therapy is a proven approach to treating tumors using alternating electric fields at frequencies between 50 kHz and 1 MHz (e.g., 150-200 kHz). See, e.g., U.S. Patent No. 7,565,205, the entire contents of which are incorporated herein by reference. Alternating electric fields are also useful for treating conditions other than tumors. For example, as described in U.S. Patent No. 10,967,167, the entire contents of which are incorporated herein by reference, alternating electric fields can be used to increase the permeability of the blood-brain barrier, allowing, for example, chemotherapy drugs to reach the brain.

[0003] FIG. 1 shows a prior art Optune® system that delivers a TT field to a patient via four transducer arrays 90 placed on the patient's skin near the tumor. The transducer arrays 90 are arranged in two pairs: one pair of transducer arrays 90L and 90R is placed on the left and right sides of the tumor, and the other pair of transducer arrays 90A and 90P is placed in front and behind the tumor. Each transducer array is connected to an AC signal generator 95 via a multi-wire cable. The AC signal generator (a) sends an AC current to the anterior / posterior (A / P) pair of transducer arrays for one second to induce an electric field in the tumor in a first direction, and then (b) sends an AC current to the left / right (L / R) pair of arrays for one second to induce an electric field in the tumor in a second direction, and then repeats steps (a) and (b) throughout the treatment. Each transducer array includes multiple electrode elements (e.g., between 9 and 30). The electrode elements on any given transducer array are then all wired together (eg, in series or parallel).

[0004] Figure 2 shows a more detailed view of a set of four transducer arrays 90, with the individual electrode elements that make up each transducer array visible. In this example, each of the transducer arrays 90 includes nine circular electrode elements supported by a self-adhesive substrate. In Figure 2, each of the four transducer arrays 90 is positioned at a specific location on the patient's head.

[0005] Increasing the strength of the AC electric field in the relevant target region (e.g., a tumor such as a glioblastoma) typically increases the effectiveness of the treatment. Also, it is always possible to increase the field strength within the target region by shifting the position of the transducer array 90 from the exact position shown in FIG. 2. More specifically, by shifting the position of the transducer array 90 on the relevant body part (e.g., by a few centimeters upward, downward, rightward, leftward, forward, and / or backward), the path of the AC electric field through the body part can be changed. Also, changing the path of the electric field can increase the field strength within the target region, which in turn can increase the effectiveness of the treatment.

[0006] However, it has been found that the degree of control over the path of the electric field that can be achieved by shifting the position of the transducer array is limited, which in turn limits the extent to which the field strength can be increased. Summary of the Invention [Means for solving the problem]

[0007] One embodiment of the present invention relates to a first device for applying an electric field to a target area using at least eight first electrode elements disposed on a first side of the target area and at least eight second electrode elements disposed on a second side of the target area opposite the first side of the target area. The first device includes at least eight electrically isolated first signal generators, each having a respective first control input. Each first signal generator is configured to apply an electrical signal between a respective one of the at least eight first electrode elements and a respective one of the at least eight second electrode elements in response to a respective first control signal arriving at the respective first control input. The first device also includes a controller programmed to generate each of the first control signals.

[0008] In some embodiments of the first device, each of the first signal generators is configured to (a) apply a positive electrical signal between a respective one of the at least eight first electrode elements and a respective one of the at least eight second electrode elements in response to a respective first control signal arriving at a respective first control input, and (b) apply a negative electrical signal between a respective one of the at least eight first electrode elements and a respective one of the at least eight second electrode elements in response to a respective second control signal arriving at a respective second control input. Note that the use of identifiers (a) and (b) does not imply that (a) must precede (b) in time.

[0009] Optionally, in the embodiment described in the previous paragraph, the controller may be further programmed to apply, for each of the first signal generators, the respective first control signal and the respective second control signal in an alternating sequence at respective times, such that each first signal generator produces an output that alternates between a positive electrical signal and a negative electrical signal.

[0010] Optionally, in the embodiment described in the previous paragraph, the controller may be further programmed to insert an interruption time between each first control signal and each second control signal.

[0011] In some embodiments of the first device, the controller is further programmed to generate each of the first control signals in a sequence that causes each of the at least eight first signal generators to generate an output having a given waveform, the output of each of the at least eight first signal generators being shifted in time relative to the output of at least one other first signal generator. Optionally, in these embodiments, the controller may be further programmed to control the time shifting to induce the electric field within the target region.

[0012] In some embodiments of the first device, the controller is further programmed to generate each of the first control signals in a sequence that causes each of the at least eight first signal generators to generate an output having a given waveform, the output of each of the at least eight first signal generators being shifted in time relative to the output of at least one other first signal generator. The controller is also further programmed to generate each of the first control signals in a sequence that causes each of the at least eight first signal generators to generate an output that alternates between a positive electrical signal and a negative electrical signal.

[0013] Some embodiments of the first device further include at least eight first electrode elements and at least eight second electrode elements.

[0014] Some embodiments of the first device further include at least eight electrically isolated second signal generators, each having a respective second control input, and each configured to apply an electrical signal between a respective one of the at least eight third electrode elements and a respective one of the at least eight fourth electrode elements in response to a respective second control signal arriving at the respective second control input. In these embodiments, the controller is further programmed to generate each of the second control signals.

[0015] Optionally, in the embodiment described in the previous paragraph, the controller may be further programmed to generate each of the first control signals in a sequence that causes each of the at least eight first signal generators to generate an output having a first given waveform, the output of each of the at least eight first signal generators being shifted in time relative to the output of at least one other first signal generator, and the controller may also be programmed to generate each of the second control signals in a sequence that causes each of the at least eight second signal generators to generate an output having a second given waveform, the output of each of the at least eight second signal generators being shifted in time relative to the output of at least one other second signal generator.

[0016] Another aspect of the present invention relates to a first method for applying an electric field to a target area using at least eight first electrode elements disposed on a first side of the target area and at least eight second electrode elements disposed on a second side of the target area opposite the first side of the target area. The first method includes applying a respective first electrical signal between a respective one of the at least eight first electrode elements and a respective one of the at least eight second electrode elements. All of the first electrical signals have a given first waveform. Each of the first electrical signals is shifted in time with respect to at least one other first electrical signal. Each of the first electrical signals is electrically isolated from all of the other first electrical signals.

[0017] In some examples of the first method, the first electrical signals are applied in a time-shifted manner to induce an electric field in the target region. Optionally, in these examples, each of the first electrical signals alternates between positive and negative polarity.

[0018] Some examples of the first method further include positioning at least eight first electrode elements on a first side of the target area and positioning at least eight second electrode elements on a second side of the target area.

[0019] Some examples of the first method further include applying a respective second electrical signal between a respective one of the at least eight third electrode elements and a respective one of the at least eight fourth electrode elements, wherein the second electrical signals all have a given second waveform, each of the second electrical signals is time-shifted relative to at least one other second electrical signal, and each of the second electrical signals is electrically isolated from all other second electrical signals.

[0020] Optionally, in the examples described in the previous paragraph, the first electrical signals are applied with a time shift to induce an electric field in the target region, and the second electrical signals are applied with a time shift to induce an electric field in the target region. Also, optionally, in these examples, each of the first electrical signals alternates between positive and negative polarity, and each of the second electrical signals alternates between positive and negative polarity. [Brief explanation of the drawings]

[0021] [Figure 1] FIG. 1 is a block diagram of a prior art Optune® system for delivering a TT field. [Figure 2] FIG. 2 is a more detailed view of the transducer array of FIG. 1. [Figure 3] A set of four transducer arrays is shown placed on the patient's skin near the tumor. [Figure 4] FIG. 4 is a block diagram of a system for applying electrical signals to electrode elements in the transducer array shown in FIG. 3. [Figure 5] It is shown that the phases of the signals generated by a set of signal generators are controlled to generate a particular set of output signals. DETAILED DESCRIPTION OF THE INVENTION

[0022] Various embodiments will now be described in detail with reference to the accompanying drawings, in which like reference numerals represent like elements, and in which:

[0023] This application discloses an alternative approach for shifting the path of an alternating electric field through an associated body part, which in many circumstances can increase the field strength in a target region beyond levels achievable using prior art approaches that shift the position of a transducer array.

[0024] More specifically, instead of using a single signal generator to apply a signal between all of the electrode elements on one side of the target region and all of the electrode elements on the other side of the target region (as in the prior art), the embodiment described below in connection with Figures 3-5 uses at least eight electrically isolated signal generators to apply an electrical signal between each electrode element on one side of the target region and each electrode element on the other side of the target region. This replaces the single wide cross-sectional electric field of the prior art with eight independently controllable electric fields, each with a relatively narrow cross-section. Using these relatively narrow cross-sectional fields alone or in combination can improve the targeting of the electric field, which in turn can increase the field strength within the target region. Optionally, activation of these relatively narrow cross-sectional fields can be shifted in time (e.g., phase-shifted) to achieve overall induction of the electric field.

[0025] FIG. 3 shows a set of four transducer arrays 10 placed on a patient's skin near a tumor. The transducer arrays 10 are arranged in two pairs: one pair of transducer arrays 10L and 10R is placed on the left and right sides of the tumor, and the other pair of transducer arrays 10A and 10P is placed in front of and behind the tumor. Each of the transducer arrays 10 is similar in most respects to the prior art Optune® transducer array 90 described above. However, unlike the Optune® transducer array, the electrode elements on any given transducer array 10 are not all wired together in series or parallel. Instead, each of the electrode elements A1-A9 on the front transducer array 10A is provided with its own individual wire so that it can be driven independently. Similarly, each of the electrode elements P1-P9, L1-L9, and R1-R9 on the rear array 10P, left array 10L, and right array 10R is provided with its own individual wire so that it can be driven independently.

[0026] Providing individual wires for each electrode element on each of the transducer arrays 10 allows individualized signals to be applied independently to each of the electrode elements on each transducer array without affecting the other electrode elements on the transducer array, and the advantages provided by this arrangement are described below.

[0027] FIG. 4 is a block diagram of a system for applying electrical signals to electrode elements A1-A9, P1-P9, L1-L9, and R1-R9 shown in FIG. 3. The system in the illustrated embodiment includes nine first signal generators X1-X9. Each of these first signal generators X1-X9 is wired to apply a signal between a respective one of electrode elements L1-L9 on the left array 10L and a respective one of electrode elements R1-R9 on the right array 10R. More specifically, signal generator Xi is wired to apply a signal between electrode element Li and electrode element Ri, where i is an integer between 1 and 9. In some embodiments, the output of any given one of first signal generators Xi can be either positive (i.e., when the respective L terminal is an anode and the respective R terminal is a cathode), negative (i.e., when the respective L terminal is a cathode and the respective R terminal is an anode), or off (i.e., when no pulse is generated).

[0028] Each of the first signal generators X1-X9 is electrically isolated from all other signal generators. As a result, the signal that signal generator X1 applies between electrode element L1 and electrode element R1 does not affect the signal applied to any of the other electrode elements L2-L9, R2-R9, A1-A9, or P1-P9. A similar situation exists for all other first signal generators X2-X9, such that the signals that those signal generators send to their respective electrode elements do not affect the signals applied to any of the other electrode elements.

[0029] Each of the first signal generators X1-X9 has a respective first control input, and each of the first signal generators X1-X9 is configured to apply an electrical signal between a respective one of the electrode elements L1-L9 and a respective one of the electrode elements R1-R9 in response to a respective first control signal arriving at the respective first control input. The controller 30 is programmed to generate each of these first control signals.

[0030] Each of the first signal generators X1-X9 can be configured to (a) apply a positive electrical signal between a respective one of the electrode elements L1-L9 and a respective one of the electrode elements R1-R9 in response to a respective first control signal arriving at a respective first control input, and (b) apply a negative electrical signal between the respective one of the electrode elements L1-L9 and a respective one of the electrode elements R1-R9 in response to a respective second control signal arriving at a respective second control input. Note that the use of identifiers (a) and (b) does not imply that (a) must precede (b) in time.

[0031] When the first signal generators are implemented as described in the previous paragraph, controller 30 can be programmed to apply, for each of first signal generators X1-X9, a respective first control signal and a respective second control signal in an alternating sequence at respective times such that each first signal generator generates an output that alternates between a positive electrical signal and a negative electrical signal. Optionally, in these embodiments, controller 30 can be further programmed to insert a pause between each first control signal and each second control signal.

[0032] The system in the described embodiment also includes nine second signal generators Y1-Y9, each wired to apply a signal between a respective single element of electrode elements A1-A9 on the front array 10A and a respective single element of electrode elements P1-P9 on the rear array 10P. More specifically, signal generator Yj is wired to apply a signal between electrode element Aj and electrode element Pj, where j is an integer between 1 and 9. In some embodiments, the output of any given one of second signal generators Yj can be either positive (i.e., when the respective A terminal is an anode and the respective P terminal is a cathode), negative (i.e., when the respective A terminal is a cathode and the respective P terminal is an anode), or off (i.e., when no pulse is generated).

[0033] Each of the second signal generators Y1-Y9 is electrically isolated from all other signal generators. As a result, the signal that signal generator Y1 applies between electrode element A1 and electrode element P1 does not affect the signal applied to any of the other electrode elements A2-A9, P2-P9, L1-L9, or R1-R9. A similar situation exists for all other second signal generators Y2-Y9, such that the signals that those signal generators send to their respective electrode elements do not affect the signals applied to any of the other electrode elements.

[0034] Each of the second signal generators Y1-Y9 has a respective second control input, and each of the second signal generators Y1-Y9 is configured to apply an electrical signal between a respective one of the electrode elements A1-A9 and a respective one of the electrode elements P1-P9 in response to a respective second control signal arriving at the respective second control input. The controller 30 is further programmed to generate each of these second control signals. The operation of the second signal generators Y1-Y9 is similar to the operation of the first signal generators X1-X9 described above.

[0035] 1, in a prior art system in which all of the electrode elements on the left transducer array 90L are wired together in series or parallel and all of the electrode elements on the right transducer array 90R are wired together in series or parallel, a single electric field propagates from all of the electrode elements on the left transducer array 90L to all of the electrode elements on the right transducer array 90R. Also, a single electric field propagates from all of the electrode elements on the front transducer array 90A to all of the electrode elements on the rear transducer array 90P. The resulting electric field therefore has a relatively large cross-section and can therefore be analogized to a floodlight.

[0036] In contrast, in the embodiment of Figures 3 / 4, when signal generator X1 is activated, one electric field propagates from electrode element L1 to electrode element R1; when signal generator X2 is activated, a second electric field propagates from electrode element L2 to electrode element R2; when signal generator X3 is activated, a third electric field propagates from electrode element L3 to electrode element R3, etc. As a result, depending on which of signal generators X1-X9 is activated, nine separate electric fields can propagate from respective electrode elements L1-L9 to respective electrode elements R1-R9. When any given one of signal generators X1-X9 is activated, the resulting electric field has a relatively small cross-section and can therefore be analogized to a spotlight.

[0037] In particular, two or more of signal generators X1-X9 can be activated simultaneously (e.g., any two at a time, any three at a time, etc., up to nine at a time). When all nine of signal generators X1-X9 are activated simultaneously, the resulting electric field has a cross-section similar to that produced using prior art transducer arrays 90L / 90R. The latter situation can be analogized to the situation where light from nine individual spotlights collectively illuminates the same area as a floodlight.

[0038] Similarly, when signal generator Y1 is activated, one electric field propagates from electrode element A1 to electrode element P1; when signal generator Y2 is activated, a second electric field propagates from electrode element A2 to electrode element P2; when signal generator Y3 is activated, a third electric field propagates from electrode element A3 to electrode element P3, etc. As a result, depending on which of signal generators Y1-Y9 is activated, nine separate electric fields can propagate from respective electrode elements A1-A9 to respective electrode elements P1-P9. When any given one of signal generators Y1-Y9 is activated, the resulting electric field has a relatively small cross-section and can therefore be analogized to a spotlight.

[0039] As discussed above with respect to first signal generators X1-X9, two or more of second signal generators Y1-Y9 can be activated simultaneously (e.g., any two at a time, any three at a time, etc., up to nine at a time). When all nine of signal generators Y1-Y9 are activated simultaneously, the resulting electric field has a cross-section similar to that produced using prior art transducer arrays 90A / 90P. This latter situation can again be analogized to the situation where light from nine individual spotlights collectively illuminates the same area as a floodlight.

[0040] Splitting the electric field into individual narrower components as described above can be very useful in focusing the field onto a target area, analogous to how nine individually controllable spotlights can focus illumination onto a given target area more effectively than a single floodlight.

[0041] Beyond the additional level of control provided by dividing the electric field into individual narrower components to concentrate the electric field on the target region, a further level of control over the electric field within the target region can be obtained by controlling the phase of the signals generated by signal generators X1-X9 and Y1-Y9.

[0042] FIG. 5 illustrates an example of how controller 30 controls the phases of signals generated by signal generators X1-X9 to cause them to generate output signals that resemble piecewise approximations to phase-shifted sine waves S1-S9. More specifically, controller 30 is programmed to generate control signals in a sequence that causes each of signal generators X1-X9 to generate an output having a given waveform, such that the output of each of signal generators X1-X9 is shifted in time relative to the output of at least one other signal generator X1-X9. An example of a control signal that controller 30 sends to signal generator X1 is shown in the bottom half of FIG. 5, where + represents a command to generate a positive signal, 0 represents a command to generate a zero output, and − represents a command to generate a negative signal. Additionally, the outputs that signal generators X1-X9 send to each set of electrode elements L1 / R1-L9 / R9 are shown in the top portion of FIG. 5.

[0043] When signal generator X1 receives the + / - / 0 control signals shown in the top row of the lower half of Figure 5, signal generator X1 generates the digital signals shown in the top row of the upper half of Figure 5. More specifically, signal generator X1 (a) applies positive signals to electrode elements L1 and R1 during time intervals 1-4, (b) applies no signal to those electrode elements during time interval 5, (c) applies negative signals to those electrode elements during time intervals 6-9, (d) applies no signal to those electrode elements during time interval 10, (e) applies positive signals to those electrode elements during time intervals 11-14, (f) applies no signal to those electrode elements during time interval 15, and (f) applies a negative signal to those electrode elements during time interval 16. Notably, overlaying sine wave S1 with the digital signals shown in the top row of Figure 5 reveals that the digital signals are first-order piecewise approximations to sine wave S1.

[0044] As shown in the bottom half of Figure 5, controller 30 sends similar signals to the other signal generators X2-X9, but shifted in time relative to the signal sent to signal generator X1. Signal generators X2-X9 respond by applying digital signals to their corresponding electrode element pairs L2 / R2-L9 / R9, as shown in the top half of Figure 5. Again, these digital signals resemble the digital signals described above for electrode elements L1 and R1, except that they are shifted in time as shown in the top half of Figure 5. Again, an overlay of the sine waves S2-S9 and the digital signals applied to electrode element pairs L2 / R2-L9 / R9 reveals that each of these digital signals is a first-order piecewise approximation of a respective one of the sine waves S2-S9, and that each of these sine waves (except S6) is phase-shifted relative to sine wave S1.

[0045] Optionally, the controller 30 can be programmed to control the time shift to direct the electric field within a target area. Under certain conditions, particularly when the number of signal generators is large, the ability to generate phase-shifted sinusoidal waves can be used to control the direction of the electric field by implementing beam steering techniques similar to those used in phased array radar systems. These techniques can therefore be used to direct the electric field toward a target area with even finer control than can be achieved using the spotlight-shaped electric field described above in connection with Figures 3-4.

[0046] The operation of the other sets of signal generators Y1 to Y9 is similar to the operation of the first set of signal generators X1 to X9 described above.

[0047] Although the FIG. 3 / 4 embodiment is described above in the context of an example including nine electrode elements A1-A9, P1-P9, L1-L9, and R1-R9 on each of the transducer arrays 10, the number of electrode elements on each of the transducer arrays 10 can vary (e.g., between 8 and 64). Similarly, instead of the nine first signal generators X1-X9 and nine second signal generators Y1-Y9 shown, the number of first signal generators X can vary (e.g., between 8 and 64), so long as there are at least eight. The number of second signal generators Y can also vary (e.g., between 8 and 64), so long as there are at least eight. The number of signal generators typically matches the number of electrode elements in the corresponding transducer array 10.

[0048] Finally, some anatomical locations use only a single pair of transducer arrays 10. In these embodiments, one bank of signal generators (e.g., Y1-Y9 in FIG. 4) and two of the transducer arrays (e.g., 10A and 10P) are omitted.

[0049] While the present invention has been disclosed with reference to several embodiments, many modifications, variations, and variations of the described embodiments are possible without departing from the field and scope of the invention, as defined in the appended claims. Accordingly, it is intended that the present invention not be limited to the described embodiments, but rather have the full scope defined by the language of the following claims and their equivalents.

Claims

1. 1. An apparatus for applying an electric field to a target area using at least eight first electrode elements disposed on a first side of the target area and at least eight second electrode elements disposed on a second side of the target area opposite the first side of the target area, the apparatus comprising: at least eight electrically isolated first signal generators, each of said first signal generators having a respective first control input, each of said first signal generators configured to apply an electrical signal between a respective one of said at least eight first electrode elements and a respective one of said at least eight second electrode elements in response to a respective first control signal arriving at said respective first control input; a controller programmed to generate each of the first control signals.

2. 2. The apparatus of claim 1, wherein each of the first signal generators is configured to (a) apply a positive electrical signal between a respective one of the at least eight first electrode elements and a respective one of the at least eight second electrode elements in response to a respective first control signal arriving at the respective first control input, and (b) apply a negative electrical signal between a respective one of the at least eight first electrode elements and a respective one of the at least eight second electrode elements in response to a respective second control signal arriving at the respective second control input.

3. 3. The apparatus of claim 2, wherein the controller is further programmed to apply, for each of the first signal generators, the respective first control signal and the respective second control signal in an alternating sequence at respective times such that the respective first signal generator produces an output that alternates between a positive electrical signal and a negative electrical signal.

4. The apparatus of claim 3 , wherein the controller is further programmed to insert a pause time between each first control signal and each second control signal.

5. 2. The apparatus of claim 1, wherein the controller is further programmed to generate each of the first control signals in a sequence that causes each of the at least eight first signal generators to produce an output having a given waveform, the output of each of the at least eight first signal generators being shifted in time relative to an output of at least one other first signal generator.

6. The apparatus of claim 5 , wherein the controller is further programmed to control the time shift to induce an electric field within the target region.

7. 6. The apparatus of claim 5, wherein the controller is further programmed to generate each of the first control signals in a sequence that causes each of the at least eight first signal generators to produce an output that alternates between a positive electrical signal and a negative electrical signal.

8. the at least eight first electrode elements; The device of claim 1 , further comprising: the at least eight second electrode elements.

9. further comprising at least eight electrically isolated second signal generators, each of said second signal generators having a respective second control input, each of said second signal generators configured to apply an electrical signal between a respective one of the at least eight third electrode elements and a respective one of the at least eight fourth electrode elements in response to a respective second control signal arriving at said respective second control input; The apparatus of claim 1 , wherein the controller is further programmed to generate each of the second control signals.

10. the controller is further programmed to generate each of the first control signals in a sequence that causes each of the at least eight ninth signal generators to produce an output having a first given waveform, the output of each of the at least eight first signal generators being shifted in time relative to the output of at least one other first signal generator; 10. The apparatus of claim 9, wherein the controller is further programmed to generate each of the second control signals in a sequence that causes each of the at least eight second signal generators to produce an output having a second given waveform, the output of each of the at least eight second signal generators being shifted in time relative to an output of at least one other second signal generator.

11. 1. A method for applying an electric field to a target area using at least eight first electrode elements disposed on a first side of the target area and at least eight second electrode elements disposed on a second side of the target area opposite the first side of the target area, the method comprising: applying a respective first electrical signal between a respective one of the at least eight first electrode elements and a respective one of the at least eight second electrode elements, wherein the first electrical signals all have a given first waveform, each of the first electrical signals is shifted in time with respect to at least one other first electrical signal, and each of the first electrical signals is electrically isolated from all other first electrical signals.

12. 12. The method of claim 11, wherein the first electrical signals are applied in a time-shifted manner to induce an electric field in the target region.

13. The method of claim 12 , wherein each of the first electrical signals alternates between positive and negative polarity.

14. positioning the at least eight first electrode elements on the first side of the target area; The method of claim 11 , further comprising: positioning the at least eight second electrode elements on the second side of the target area.

15. 12. The method of claim 11, further comprising applying a respective second electrical signal between a respective one of the at least eight third electrode elements and a respective one of the at least eight fourth electrode elements, the second electrical signals all having a given second waveform, each of the second electrical signals being shifted in time with respect to at least one other second electrical signal, and each of the second electrical signals being electrically isolated from all other second electrical signals.

16. the first electrical signals are applied in a time-shifted manner to induce an electric field in the target region; 16. The method of claim 15, wherein the second electrical signals are applied in a time-shifted manner to induce an electric field in the target region.

17. each of the first electrical signals alternates between positive and negative polarity; 17. The method of claim 16, wherein each of the second electrical signals alternates between positive and negative polarity.

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