Array for longitudinal delivery of TT fields to the human body

Abstract

Tumors in a portion of a subject's body having a longitudinal axis (e.g., a trunk, head, and arm) can be treated with a TT field by attaching a first set of electrodes and a second set of electrodes at corresponding locations before and after a target area. An AC voltage having a frequency of 100 kHz to 500 kHz is applied between these electrode sets. This imposes an AC electric field having field lines that extend longitudinally through the target area. In at least a portion of the target area, the field strength is at least 1 V / cm. In some embodiments, the method is combined with applying an AC electric field through the target area in a lateral direction (e.g., from front to back and / or from side to side) so that AC electric fields with different orientations are applied to the target area.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of U.S. Provisional Application No. 62 / 356,986, filed June 30, 2016, which is incorporated herein by reference in its entirety. Background Art

[0003] Tumor treatment fields (TT fields) are low-intensity alternating electric fields (e.g., 1-3 V / cm) in the medium frequency range (e.g., 125 kHz to 250 kHz, or in some cases 100 kHz to 500 kHz) that target solid tumors by disrupting mitosis. TT fields are generally delivered through two pairs of electrode arrays. The electrode arrays that make up each of these pairs are positioned on opposite sides of the body part being treated. Figure 1A and Figure 1B The conventional positioning of the electrode arrays on the head and chest of the subject are depicted, respectively. In each of these examples, the first pair of electrode arrays includes one electrode array at the anterior position 16 / 19 and a second electrode array at the posterior position (not shown, but located directly behind the corresponding anterior position). When an AC voltage is applied between the anterior electrode array and the posterior electrode array, the field lines of the generated electric field will generally extend between the front and back of the subject.

[0004] Figure 1A and Figure 1B Each of the examples also includes a second pair of electrode arrays, including one electrode array at right positions 14 / 17 and a second electrode array at left positions 15 / 18. When an AC voltage is applied between the right array and the left array, the field lines of the generated electric field will generally extend between the left and right sides of the subject. The AC voltage is applied in an alternating sequence between (i) the anterior / posterior (A / P) electrode array and (ii) the right / left (R / L) electrode array so that the direction of the field will repeatedly switch between the above two directions (e.g., every 1 second).

[0005] Although the A / P electrode array and the R / L electrode array are well suited for applying electric fields to many parts of a subject's body in two generally perpendicular directions, many situations can be envisioned where the A / P electrodes and the R / L electrodes may be difficult or impossible to use. Examples include situations where the subject has a sore or ulcer at one of the common sites for positioning the electrode array, and situations where treating a tumor at a location where using both the A / P electrodes and the R / L electrodes would be uncomfortable and / or impractical (e.g., at the subject's neck, elbow, knee, etc.). Summary of the invention

[0006] One aspect of the invention relates to a first device for treating a target area in a subject's body with a TT field, the target area being located in a portion of the subject's body having a longitudinal axis. The device includes a first set of one or more capacitively coupled electrodes and a first substrate, the first substrate being configured to hold the first set of one or more electrodes against the subject's body so that the first set of one or more electrodes surrounds a first portion of the subject's body at a position longitudinally located before the target area. The device also includes a second set of one or more capacitively coupled electrodes and a second substrate, the second substrate being configured to hold the second set of one or more electrodes against the subject's body so that the second set of one or more electrodes surrounds a second portion of the subject's body at a position longitudinally located after the target area. The device also includes a third set of one or more capacitively coupled electrodes and a third substrate, the third substrate being configured to hold the third set of one or more electrodes against the subject's body on a first side of the target area at a position longitudinally located between the first set of one or more electrodes and the second set of one or more electrodes. The device also includes a fourth set of one or more capacitively coupled electrodes and a fourth substrate, the fourth substrate being configured to hold the fourth set of one or more electrodes against the subject's body on a second side of the target area opposite to the first side at a position longitudinally located between the first set of one or more electrodes and the second set of one or more electrodes.

[0007] Some embodiments of the first device further include an AC voltage generator configured to generate, in a repeating and alternating sequence, (a) an AC voltage having a frequency of 100 kHz to 500 kHz between the first group of one or more electrodes and the second group of one or more electrodes, and (b) an AC voltage having a frequency of 100 kHz to 500 kHz between the third group of one or more electrodes and the fourth group of one or more electrodes.

[0008] Some embodiments of the first device further include an AC voltage generator configured to generate, in a repeating and alternating sequence, (a) an AC voltage having a frequency of 125 kHz to 250 kHz between the first group of one or more electrodes and the second group of one or more electrodes, and (b) an AC voltage having a frequency of 125 kHz to 250 kHz between the third group of one or more electrodes and the fourth group of one or more electrodes.

[0009] In some embodiments of the first device, the first set of one or more electrodes includes a first plurality of flat electrode elements, and the second set of one or more electrodes includes a second plurality of flat electrode elements. In some of these embodiments, each of the first substrate and the second substrate is flexible.

[0010] In some embodiments of the first device, each of the first substrate and the second substrate is shaped and sized to fit around the torso of the subject. In some embodiments of the first device, the first substrate is shaped and sized to fit around the torso of the subject, and the second substrate is shaped and sized to fit around the neck of the subject. In some embodiments of the first device, the first substrate is shaped and sized to fit around the neck of the subject, and the second substrate is shaped and sized to fit around the head of the subject. In some embodiments of the first device, the first substrate is shaped and sized to fit around the neck of the subject, and the second substrate is shaped and sized to fit on the head of the subject. In some embodiments of the first device, each of the first substrate and the second substrate is shaped and sized to fit around a limb of the subject.

[0011] Some embodiments of the first device further include a fifth set of one or more capacitive coupling electrodes and a fifth substrate configured to hold the fifth set of one or more electrodes against the subject's body on a third side of the target area at a position longitudinally between the first set of one or more electrodes and the second set of one or more electrodes. These embodiments still further include a sixth set of one or more capacitive coupling electrodes and a sixth substrate configured to hold the sixth set of one or more electrodes against the subject's body on a fourth side of the target area opposite the third side at a position longitudinally between the first set of one or more electrodes and the second set of one or more electrodes.

[0012] Another aspect of the invention relates to a first method of treating a target area in a subject's body with a TT field, the target area being located in a portion of the subject's body having a longitudinal axis. The method includes attaching a first set of one or more electrodes to the subject's body so as to surround a first portion of the subject's body at a position longitudinally anterior to the target area; and attaching a second set of one or more electrodes to the subject's body so as to surround a second portion of the subject's body at a position longitudinally posterior to the target area. The method also includes applying a first AC voltage of a frequency of 100 kHz to 500 kHz between the first set of one or more electrodes and the second set of one or more electrodes so as to impose a first AC electric field having field lines extending longitudinally through the target area, the first AC electric field having a field strength of at least 1 V / cm in at least a portion of the target area.

[0013] In some embodiments of the first method, the first set of one or more electrodes and the second set of one or more electrodes are capacitively coupled to the body of the subject.

[0014] Some embodiments of the first method further include attaching a third set of one or more electrodes to the subject's body on a first side of the target area at a position longitudinally between the first set of one or more electrodes and the second set of one or more electrodes, and attaching a fourth set of one or more electrodes to the subject's body on a second side of the target area opposite to the first side at a position longitudinally between the first set of one or more electrodes and the second set of one or more electrodes. These methods further include applying a second AC voltage having a frequency of 100kHz to 500kHz between the third set of one or more electrodes and the fourth set of one or more electrodes so as to impose a second AC electric field through the target area, the second AC electric field having a field strength of at least 1V / cm in at least a portion of the target area. In some of these embodiments, each of the first, second, third, and fourth sets of one or more electrodes is capacitively coupled to the subject's body. In some of these embodiments, each of the first AC voltage and the second AC voltage has a frequency of 125kHz to 250kHz. In some of these embodiments, the steps of applying the first AC voltage and applying the second AC voltage are repeated at least 10,000 times in an alternating sequence.

[0015] Some embodiments of the first method further include attaching a fifth set of one or more electrodes to the subject's body on a third side of the target area at a location longitudinally between the first set of one or more electrodes and the second set of one or more electrodes; and attaching a sixth set of one or more electrodes to the subject's body on a fourth side of the target area opposite to the third side at a location longitudinally between the first set of one or more electrodes and the second set of one or more electrodes. These embodiments further include applying a third AC voltage with a frequency of 100 kHz to 500 kHz between the fifth set of one or more electrodes and the sixth set of one or more electrodes so as to impose a third AC electric field through the target area, the third AC electric field having a field strength of at least 1 V / cm in at least a portion of the target area. In some of these embodiments, the steps of applying the first AC voltage, applying the second AC voltage, and applying the third AC voltage are repeated at least 10,000 times in an alternating order.

[0016] In some embodiments of the first method, the first set of one or more electrodes includes a first plurality of flat electrode elements distributed around a first portion of the subject's body, and the second set of one or more electrodes includes a second plurality of flat electrode elements distributed around a second portion of the subject's body.

[0017] In some embodiments of the first method, the target area is located in the subject's torso, a first set of one or more electrodes are positioned around the subject's torso below the target area, and a second set of one or more electrodes are positioned around the subject's torso above the target area.

[0018] In some embodiments of the first method, the target area is located in the torso of the subject, the first set of one or more electrodes are positioned around the torso of the subject below the target area, and the second set of one or more electrodes are positioned around the neck of the subject.

[0019] In some embodiments of the first method, the target area is located in the subject's head, the first set of one or more electrodes are positioned around the subject's neck, and the second set of one or more electrodes are positioned around the subject's head.

[0020] In some embodiments of the first method, the target area is located in a limb of the subject. In these embodiments, the longitudinal axis extends through the limb in a proximal to distal direction, a first set of one or more electrodes are positioned around the limb at a location proximal to the target area, and a second set of one or more electrodes are positioned around the limb at a location distal to the target area.

[0021] Another aspect of the present invention relates to a second device for treating a target area in a limb of a subject's body with a TT field. The device includes a first set of one or more capacitively coupled electrodes, and a first substrate configured to hold the first set of one or more electrodes against the subject's body so that the first set of one or more electrodes partially surrounds a first side of the limb at a location proximal to the target area. The device also includes a second set of one or more capacitively coupled electrodes and a second substrate configured to hold the second set of one or more electrodes against the subject's body so that the second set of one or more electrodes partially surrounds a second side of the limb at a location distal to the target area. The second side of the limb is opposite to the first side of the limb. The device also includes a third set of one or more capacitively coupled electrodes and a third substrate configured to hold the third set of one or more electrodes against the subject's body so that the third set of one or more electrodes partially surrounds the second side of the limb at a location proximal to the target area. The device also includes a fourth set of one or more capacitively coupled electrodes and a fourth substrate configured to hold the fourth set of one or more electrodes against the subject's body so that the fourth set of one or more electrodes partially surrounds the first side of the limb at a location distal to the target area.

[0022] Some embodiments of the second device further include an AC voltage generator configured to generate (a) a first AC voltage having a frequency of 100 kHz to 500 kHz between the first set of one or more electrodes and the second set of one or more electrodes, and (b) a second AC voltage having a frequency of 100 kHz to 500 kHz between the third set of one or more electrodes and the fourth set of one or more electrodes in a repeating and alternating sequence. In some of these embodiments, each of the first AC voltage and the second AC voltage has a frequency of 125 kHz to 250 kHz.

[0023] In some embodiments of the second device, each of the first, second, third, and fourth sets of one or more electrodes comprises a plurality of flat electrode elements. In some of these embodiments, each of the first, second, third, and fourth substrates is flexible.

[0024] In some embodiments of the second device, the limb is an arm, each of the first and third baseplates is shaped and sized to fit on the arm proximally relative to the elbow, and each of the second and fourth baseplates is shaped and sized to fit on the arm distally relative to the elbow. In some embodiments of the second device, the limb is a leg, each of the first and third baseplates is shaped and sized to fit on the leg proximally relative to the knee, and each of the second and fourth baseplates is shaped and sized to fit on the leg distally relative to the knee.

[0025] Another aspect of the invention relates to a second method of treating a target area in a limb of a subject's body with a TT field. The method includes attaching a first set of one or more electrodes to partially surround a first side of the limb at a location proximal to the target area, and attaching a second set of one or more electrodes to partially surround a second side of the limb at a location distal to the target area, wherein the second side of the limb is opposite to the first side of the limb. The method also includes attaching a third set of one or more electrodes to partially surround the second side of the limb at a location proximal to the target area, and attaching a fourth set of one or more electrodes to partially surround the first side of the limb at a location distal to the target area. The method also includes applying a first AC voltage having a frequency of 100 kHz to 500 kHz between the first set of one or more electrodes and the second set of one or more electrodes to impose a first AC electric field through the target area, the first AC electric field having a field strength of at least 1 V / cm in at least a portion of the target area; and applying a second AC voltage having a frequency of 100 kHz to 500 kHz between the third set of one or more electrodes and the fourth set of one or more electrodes to impose a second AC electric field through the target area, the second AC electric field having a field strength of at least 1 V / cm in at least a portion of the target area. In the method, the steps of applying the first AC voltage and applying the second AC voltage are performed in a repeated and alternating order.

[0026] In some embodiments of the second method, each of the first, second, third, and fourth sets of one or more electrodes is capacitively coupled to the subject's body. In some of these embodiments, each of the first AC voltage and the second AC voltage has a frequency of 125 kHz to 250 kHz.

[0027] In some embodiments of the second method, the steps of applying the first AC voltage and applying the second AC voltage are repeated at least 10,000 times in an alternating sequence.

[0028] In some embodiments of the second method, the limb is an arm, the first set of one or more electrodes and the third set of one or more electrodes are positioned proximally relative to the elbow, and the second set of one or more electrodes and the fourth set of one or more electrodes are positioned distally relative to the elbow. In some embodiments of the second method, the limb is a leg, the first set of one or more electrodes and the third set of one or more electrodes are positioned proximally relative to the knee, and the second set of one or more electrodes and the fourth set of one or more electrodes are positioned distally relative to the knee.

[0029] In some embodiments of the second method, each of the first, second, third, and fourth sets of one or more electrodes includes a plurality of flat electrode elements. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1A and Figure 1B Depicted are the conventional positioning of the electrode array on the subject's head and chest, respectively.

[0031] Figure 2 A schematic diagram depicting how longitudinal electrode pairs can be used to generate a longitudinal electric field in a cylinder.

[0032] Figure 3A Depicted are the positioning of longitudinal electrode array pairs for delivering electric fields to the thorax or abdomen.

[0033] Figure 3B Depicted is the positioning of a longitudinal electrode array pair for delivering electric fields to the abdomen.

[0034] Figure 3C Depicted is the positioning of a pair of longitudinal electrode arrays for delivering an electric field to a portion of an arm.

[0035] Figure 3D Depicted is the positioning of a pair of longitudinal electrode arrays for delivering an electric field to a portion of the leg.

[0036] Figure 3E Depicted are the positioning of pairs of longitudinal electrode arrays used to deliver electric fields to the infratentorial brain, brainstem, and neck.

[0037] Figure 3F Another embodiment for delivering electric fields to the infratentorial brain, brainstem, and neck is depicted.

[0038] Figure 4A and Figure 4B Anterior and posterior views of combining a pair of longitudinal arrays with a pair of anterior / posterior lateral arrays to deliver a field to the thorax or abdomen are depicted, respectively.

[0039] Figure 4C and Figure 4DDepicted are anterior and posterior views of combining a pair of longitudinal arrays with a pair of left / right transverse arrays to deliver a field to the thorax or abdomen, respectively.

[0040] Figure 4E and Figure 4F Depicted are the anterior and posterior views, respectively, of a pair of longitudinal arrays combined with a pair of diagonally positioned transverse arrays to deliver the field to the thorax.

[0041] Figure 4G Depicted is a posterior view of a pair of longitudinal arrays combined with a pair of left / right lateral arrays to deliver fields to the infratentorial brain.

[0042] Figure 4H Describes a method for combining a longitudinal array with a transverse array to Figure 4G Rear view of another embodiment used in the same anatomical location.

[0043] Figure 5A and Figure 5B Depicted are the anterior and posterior views, respectively, of a pair of longitudinal arrays combined with anterior / posterior lateral arrays and left / right lateral arrays to deliver a field to the thorax.

[0044] Figure 5C and Figure 5D Depicted are the anterior and posterior views, respectively, of a pair of longitudinal arrays combined with two pairs of diagonally positioned transverse arrays to deliver the field to the thorax.

[0045] Fig. 6A A first configuration suitable for attaching a band or belt-like electrode set to a subject's body is depicted.

[0046] Figure 6B A second configuration suitable for attaching a plate-shaped electrode set to a subject's body is depicted.

[0047] Fig. 7A and Figure 7B Front and rear views, respectively, depict positioning of multiple electrode elements for one example of a pair of longitudinal arrays.

[0048] Figure 7C and Fig.7D Front and rear views, respectively, depict positioning of multiple electrode elements for one example of a pair of anterior / posterior lateral arrays.

[0049] Fig. 7E and Figure 7F Front and back views, respectively, depict positioning of multiple electrode elements for one example of a pair of left / right lateral arrays.

[0050] Figure 8 Describes the use Fig. 7A / Figure 7BElectric field strength of six axial slices located, as calculated using finite element simulations.

[0051] Fig.9A and Fig. 9B Depicted are used for Fig. 7A / Figure 7B Position the direction of the field lines of the longitudinal field through the body and lungs.

[0052] Fig. 10A and Fig. 10B Depicted are internal and external views, respectively, of an embodiment for delivering a field to the knee using two pairs of longitudinal arrays.

[0053] Various embodiments are described in detail below with reference to the drawings, wherein like reference numerals refer to like elements. DETAILED DESCRIPTION

[0054] The embodiments described below overcome the above limitations of using A / P and R / L electrodes by including at least one pair of electrode arrays configured to generate a longitudinal field in a target area. Note that as used herein: (1) in the case of the head and major part of the body, the longitudinal axis is perpendicular to both the anterior-posterior axis and the lateral axis; (2) in the case of a leg or arm, the longitudinal axis is the proximal-distal axis; (3) the term "longitudinal field" refers to a field extending in the same general direction as the longitudinal axis, and is not limited to a field that is completely parallel to the longitudinal axis; (4) an electrode array designed to generate a longitudinal field is referred to as a "longitudinal array"; and (5) a conventional electrode array designed to generate a field extending generally between the left and right sides of a subject or between the front and back of a subject is referred to as a "lateral array".

[0055] To generate a longitudinal field, a pair of annular or arc-shaped electrode arrays assembled around the subject's body can be used, with one array positioned above the other. In some embodiments, the arrays are designed as a ring that completely surrounds the body part on which they are placed. In other embodiments, the arrays are designed as an arc (e.g., a semicircle) that partially surrounds the body part on which they are placed. When a voltage is applied between the upper electrode array and the lower electrode array, the electric field generated between them will be longitudinally oriented.

[0056] Figure 2A schematic diagram depicting a first order estimate of how the longitudinal field may be generated in the body. In this example, we consider the electric field in a solid conductive cylinder 20 when an AC voltage 25 is applied between thin annular electrode rings 21, 22 on either end of the cylinder 20. The results show that the electric field generated in the cylinder 20 will be directed almost uniformly along the longitudinal direction of the cylinder, as shown by the field lines 26, and will also penetrate into the interior of the cylinder 20. In some embodiments, the electrode array pair for delivering the TT field can be designed as two annular arrays assembled around the subject's body, with one array placed above the other.

[0057] The use of longitudinal fields can provide significant advantages, as the TT fields are more effective when they are parallel to the axis of cell division. As a result, increasing the number of directions in which the field is applied can increase effectiveness against the tumor being treated (where the orientation of cells can vary during division). Notably, the use of longitudinal arrays provides new options for array placement on the body that can optimize both field distribution and subject comfort.

[0058] FIG. 3A to FIG. 3D Four examples of longitudinal electrode array pairs designed to deliver TT fields to different parts of the human body are depicted. In all of these embodiments, each of the electrode arrays includes one or more electrode elements mounted on a substrate that is configured to hold the electrode elements against the subject's body so that the electrode elements completely surround the corresponding body part. In some preferred embodiments, the substrate is flexible to facilitate conformity to the subject's body. Fig. 6A and Figure 6B Examples of suitable methods for mounting individual electrode elements on a flexible substrate are described.

[0059] exist Figure 3A In an embodiment of the invention (which is intended, for example, for delivering a field to the chest or abdomen), a first electrode array is placed at location 31 around the torso (e.g., just above the subject's waist), and a second electrode array is placed at location 32 around the subject's neck. Figure 3B In an embodiment of the invention (which is intended, for example, for delivering fields to the abdomen), a first electrode array is placed at location 33 about the torso (e.g., just above the subject's waist), and a second electrode array is placed at location 34 about the torso (e.g., on top of the subject's abdomen). In an alternative embodiment (not shown), for example, for delivering fields to the lungs, a first electrode array is placed below the chest (similar to Figure 3B 34) and a second electrode array is placed around the subject's neck (similar to Figure 3A position 32).

[0060] exist Figure 3CIn an embodiment of the invention (which is intended, for example, for delivering a field to a portion of an arm), a first electrode array is placed at a location 35 on the arm proximal to the target area, and a second electrode array is placed at a location 36 on the arm distal to the target area. The positioning of these locations 35, 36 can be adjusted to accommodate a target area within the elbow. Similarly, in Figure 3D In an embodiment, which is intended, for example, for delivering a field to a portion of a leg, a first electrode array is placed at a location 37 on the leg proximal to the target area, and a second electrode array is placed at a location 38 on the leg distal to the target area. The locations of these locations 37, 38 can be adjusted to accommodate the target area within the knee.

[0061] exist Figure 3E In an embodiment (which is intended, for example, for delivering TT fields to the infratentorial brain, brainstem, and neck), a first electrode array is placed at location 26 around the subject's neck and a second electrode array is placed at location 27 near the crown of the subject's head. Figure 3F In an embodiment (which is an alternative embodiment intended for delivering fields to these same anatomical locations), a first electrode array is placed at location 28 around the subject's neck and a second electrode array is placed at location 29 on the top of the subject's head.

[0062] FIG. 3A to FIG. 3E Each of the embodiments depicted in the can be used to implement a method of treating a target area in a subject's body using a TT field by: (1) attaching a first set of one or more electrodes to the subject's body so as to surround a first portion of the subject's body at a position longitudinally anterior to the target area; (2) attaching a second set of one or more electrodes to the subject's body so as to surround a second portion of the subject's body at a position longitudinally posterior to the target area; and (3) applying a first AC voltage having a frequency of 100 kHz to 500 kHz between the first set of one or more electrodes and the second set of one or more electrodes so as to impose a first AC electric field having field lines extending longitudinally through the target area, the first AC electric field having a field strength of at least 1 V / cm in at least a portion of the target area. In some preferred embodiments, the first set of one or more electrodes and the second set of one or more electrodes are capacitively coupled to the subject's body.

[0063] Depending on the anatomical location in which they are used, longitudinal arrays may provide one or more of the following advantages. First, longitudinal arrays may enable coverage of certain target areas with higher field strengths than transverse arrays. For example, when treating a lung tumor using only conventional transverse arrays, the array on the side of the subject must be positioned below the armpit. As a result, the field strength in the upper lobe of the lung is relatively low. In contrast, longitudinal arrays positioned around the waist and around the neck (e.g., Figure 3A) can provide a more uniform high field strength throughout the lung (as shown in the following combination Figure 8 and FIG. 9A to FIG. 9B described).

[0064] Second, in certain anatomical locations, the longitudinal array may adhere better to the contours of the body than the transverse array. For example, when treating the thorax, a transverse array placed on the chest may not adhere well to the contours of the body (e.g., in the case of a female breast), resulting in suboptimal electrical contact between the array and the body, thereby reducing the field strength in the tumor. In these cases, electrically coupling the field to the body through the longitudinal array may provide better coverage than electrical coupling of the field to the body through the transverse array.

[0065] Third, a large transverse array placed on the subject's body may restrict movement or cause discomfort to the subject in certain anatomical locations. For example, when treating the thoracic cavity, a large transverse array placed on the subject's chest (e.g., FIG. 4A to FIG. 4B In these cases, using a pair of properly designed longitudinal arrays (e.g., Figure 3A Delivering the field as described in ) can help improve comfort because a longitudinal array pair, where one array passes around the neck and one passes around the upper abdomen or waist, can be more comfortable for the subject to use.

[0066] A fourth significant advantage is that the electric field generated using a longitudinal array is substantially perpendicular to the electric field generated by a transverse array (i.e., an array of electrodes positioned anteroposteriorly or laterally). FIG. 3A to FIG. 3D The availability of longitudinal arrays also provides additional freedom in finding electrode layouts that optimize field distribution and subject comfort.

[0067] 4A to 4H Depicts a pair of longitudinal arrays (e.g., similar to the above combination FIG. 3A to FIG. 3FIn each of these cases, after the electrodes are attached to their respective positions, (a) an AC voltage is applied between the first and second groups of electrodes arranged longitudinally so as to impose a longitudinal field in the target area, and (b) an AC voltage is applied between the third and fourth groups of electrodes arranged transversely so as to impose a transverse field in the target area. These steps (a) and (b) are repeated in an alternating order over the duration of the treatment so as to repeatedly switch the direction of the field imposed in the target area. In some embodiments, the switching rate is between 0.25 seconds and 2 seconds. Because the treatment is preferably performed for several hours at a time, each of these steps (a) and (b) is preferably repeated at least 10,000 times. Preferably, the frequency of the AC voltage is between 100kHz and 500kHz, and in some preferred embodiments, the frequency is between 125kHz and 250kHz. In some preferred embodiments (e.g., for treating pancreatic cancer and certain types of lung cancer), the frequency is between 140kHz and 160kHz. In some preferred embodiments (eg, for treating ovarian cancer), the frequency is between 190 kHz and 210 kHz.Preferably, each of the electric fields imposed in the target area has a field strength of at least 1 V / cm.

[0068] exist Figure 4A / Figure 4B In an embodiment (which is intended, for example, for delivering a field to the chest), the longitudinal array is implemented by placing a first electrode array at a position 31 just above the waist of the subject and a second electrode array at a position 32 around the neck of the subject. In addition, a transverse array is provided with a third electrode array and a fourth electrode array, wherein the third electrode array is placed at a position 41 on the chest of the subject and the fourth electrode array is placed at a position 42 on the back of the subject. In this embodiment, the direction of the field lines of the transverse field extends from front to back.

[0069] exist Figure 4C / Figure 4D In an embodiment (which is also intended, for example, for use in delivering fields to the chest cavity), the longitudinal array is arranged with Figure 4A / Figure 4B , but the transverse array is implemented by placing the third electrode array at position 43 on the right side of the subject and the fourth electrode array at position 44 on the left side of the subject. In this embodiment, the direction of the field lines of the transverse field will extend from one side to the other.

[0070] exist Figure 4E / Figure 4F In an embodiment (which is also intended, for example, for use in delivering fields to the chest cavity), the longitudinal array is arranged with Figure 4A / Figure 4B4, but the transverse array is implemented by placing the third electrode array at position 45 on the left side of the subject's chest and the fourth electrode array at position 46 on the right side of the subject's back. In this embodiment, the direction of the field lines of the transverse field will extend diagonally from front to back across the subject's chest.

[0071] exist Figure 4G In an embodiment (which is intended, for example, for delivering a TT field to the infratentorial brain), the longitudinal array is implemented by placing a first electrode array at a position 26 around the subject's neck and a second electrode array at a position 27 near the crown of the subject's head. In addition, a transverse array is provided with a third electrode array and a fourth electrode array, wherein the third electrode array is placed at a position 47 on the left side of the subject's head and the fourth electrode array is placed at a position 48 on the right side of the subject's head. In this embodiment, the direction of the field lines of the transverse field will extend from one side to the other. Alternatively, the transverse array may be provided using a third electrode and a fourth electrode (not shown) placed at positions on the front and back of the subject's head.

[0072] Figure 4H Example similar to Figure 4G Embodiment, except that the longitudinal array is implemented by placing a first electrode array at location 28 around the subject's neck and a second electrode array at location 29 on the top of the subject's head.

[0073] Note that in addition to the above combination 4A to 4H In addition to the described embodiments, various alternative configurations combining a pair of longitudinally positioned arrays with a pair of transversely positioned arrays may be readily envisioned for use in a wide variety of anatomical locations, as will be apparent to one skilled in the relevant art.

[0074] FIG. 5A to FIG. 5D Depicts a pair of longitudinal arrays (e.g., similar to the above combination FIG. 3A to FIG. 3FExamples of combinations of two pairs of transverse arrays are described in conjunction with (i) and (ii) two pairs of transverse arrays. In each of these cases, (a) an AC voltage is applied between a first set of electrodes and a second set of electrodes arranged longitudinally so as to impose a longitudinal field in the target area, (b) an AC voltage is applied between a third set of electrodes and a fourth set of electrodes arranged transversely so as to impose a first transverse field in the target area; and (c) an AC voltage is applied between a fifth set of electrodes and a sixth set of electrodes arranged transversely so as to impose a second transverse field in the target area. The angle between the first transverse field and the second transverse field is preferably between 60° and 120°, and most preferably as close to 90° as possible. These steps (a), (b) and (c) are repeated in alternating order for the duration of the treatment so as to repeatedly switch the direction of the field imposed in the target area between each of the three directions. In some embodiments, the switching rate is between 0.25 seconds and 2 seconds. Because the treatment is preferably performed for several hours at a time, each of these steps (a), (b) and (c) is preferably repeated at least 10,000 times.

[0075] exist Figure 5A / FIG. B embodiment (which is intended, for example, for delivering a field to the chest), the longitudinal array is implemented by placing a first electrode array at position 31 just above the subject's waist and a second electrode array at position 32 around the subject's neck. Additionally, the first transverse array is provided with a third electrode array and a fourth electrode array, the third electrode array being placed at position 41 on the subject's chest and the fourth electrode array being placed at position 42 on the subject's back, so as to generate a first transverse field having field lines extending from front to back. Finally, the third transverse array is provided with a fifth electrode array and a sixth electrode array, wherein the fifth electrode array is placed at position 51 on the right side of the subject's body and the sixth electrode array is placed at position 52 on the left side of the subject's body, so as to generate a second transverse field having field lines extending from side to side.

[0076] Figure 5C / Figure 5D Example similar to Figure 5A / Figure 5B Embodiment, except that the third and fourth electrode arrays are placed at positions 55 and 56 on the front and back of the subject, respectively; the fifth and sixth electrode arrays are placed at positions 57 and 58 on the front and back of the subject, respectively. In this embodiment, the first transverse field will have field lines extending from the right front to the left rear; and the second transverse field will have field lines extending from the left front to the right rear. The angle between the first transverse field and the second transverse field is preferably between 60° and 120°, and most preferably as close to 90° as possible.

[0077] Here again, in addition to the above combination FIG. 5A to FIG. 5DIn addition to the two embodiments described, various alternative configurations combining a pair of longitudinally positioned arrays with two pairs of transversely positioned arrays may be readily envisioned for use in a wide range of anatomical locations, as will be apparent to one skilled in the relevant art.

[0078] The above discussion of FIGS. 3-5 explains where the various sets of electrodes are placed on the subject's body, but does not describe the construction of these electrode sets. Various structures for implementing these electrode sets may be used, including but not limited to Fig. 6A and Figure 6B The configuration shown in .

[0079] Fig. 6A A first configuration suitable for attaching a set of electrodes 60 to a subject's body is depicted. In this embodiment, each set of electrodes 60 includes a plurality of individual electrode elements 61 mounted on a strip substrate 62. The strip substrate 62 is shaped and sized to fit on the particular body part to be used. For example, for Figure 3A For the longitudinal array depicted at position 31 in FIG. 1 , substrate 62 will be a flexible substrate similar to a belt; Figure 3A For the longitudinal array depicted at position 32 in FIG. 1 , substrate 62 will be a flexible substrate similar to a collar; and for Figure 3E The longitudinal array depicted at position 27 in the figure, the substrate 62 will be a flexible substrate similar to a headband; etc. The function of the substrate 62 is to hold the individual electrode elements 61 against the subject's skin so that these elements are in good contact with the skin. Optionally, a conductive gel can be applied between the electrode elements 61 and the subject's skin.

[0080] In some embodiments, each of the individual electrode elements 61 is a disk-shaped capacitive coupling electrode having a high dielectric constant, such as the electrode elements used in a conventional Novocure TTF-100L transducer array. In an alternative embodiment, instead of using a plurality of individual electrode elements 61, a single electrode element (not shown) may be used, in which case the single electrode element is preferably flexible or contoured to conform to the specific part of the subject's body on which it is to be used.

[0081] The individual electrode elements 61 within each set of electrodes 60 are wired together using appropriate wiring 63. For example, the individual electrode elements 61 may be wired in parallel, in series, or in a combination of parallel / series. Optionally, the wiring 63 may terminate at a connector 64. The connector 64 may be used to connect the set of electrodes 60 to an AC signal generator 65 so that the AC signal generator 65 can apply a voltage between the two sets of electrodes.

[0082] Figure 6B A second configuration suitable for attaching a plate-like electrode set 60' to a subject's body is depicted. The configuration includes a plurality of individual electrode elements 61 mounted on a plate-like substrate 62'. Figure 6B The wiring 63 and the connector 64 in the embodiment are similar to Fig. 6A The corresponding element in Figure 6B Embodiments are best suited for placement in locations 41 to 58 (shown in FIGS. 4-5 ) and for use in generating the lateral fields described above in connection with those embodiments.

[0083] Various alternative substrate configurations for mounting a plurality of individual electrode elements will be apparent to those skilled in the relevant art(s) based on the anatomical locations at which the electrode elements are located. 7A to 7F The positioning of electrode elements in three such configurations is depicted. Fig. 7A / Figure 7B The substrate of the electrode elements of the longitudinal electrode groups 71, 72 shown in FIG. 1 (front and rear views, respectively) will be similar to Fig. 6A The band configuration shown in Figure 1 is scaled to the appropriate dimensions for the relevant anatomy. Figure 7C / Fig.7D The front / rear transverse electrode groups 73 / 74 and Fig. 7E / Figure 7F The substrate of the electrode elements of the right / left lateral electrode groups 75 / 76 shown in FIG. 1 (front and rear views, respectively) will be similar to Figure 6B The plate-like configuration shown in is scaled and shaped to the appropriate dimensions for the relevant anatomy. Fig. 7A / Figure 7B , Figure 7C / Fig.7D and Fig. 7E / Figure 7F Combining all three electrode configurations and circulating the field between the three pairs of electrodes to provide three different field directions can provide excellent field coverage of the upper lobe of the lungs while maintaining patient comfort.

[0084] Finite element method calculations show that the longitudinal array can provide effective penetration of the relevant anatomical structures. In one example, a plurality of ceramic disc-shaped electrode elements are distributed at a first position 71 corresponding to the waist and at a first position 72 corresponding to the waist. Fig. 7A / Figure 7B The neck of the real computational phantom is depicted at a second position 72 .

[0085] Figure 8 The electric field strength of this example is depicted, as calculated using finite element simulation, for axial slices 81 to 86, which are spaced at regular vertical intervals through the lung. The simulation shows that field strengths between 1 V / cm and 4 V / cm field strengths can be obtained in most of the lung using the longitudinal array. Fig.9A / Fig. 9B The directions of the field lines of the longitudinal field through the body and the lungs, respectively, for the simulation are depicted 91. These figures illustrate the longitudinal nature of these field lines.

[0086] In some cases, using at least one pair of longitudinal arrays may be the only practical way to treat a tumor using TT fields. For example, if the tumor is located in a joint such as the knee or elbow, using only transverse electrode sets may significantly impede the subject's mobility.

[0087] Fig. 10A and Fig. 10B Depicted are interior and exterior views, respectively, of an embodiment intended for delivering fields to the knee using two pairs of longitudinal arrays that overcome this mobility problem. In this embodiment, a first substrate holds a first set of one or more electrodes against the leg such that they partially surround the front of the leg at a location 101 proximal to the knee, a second substrate holds a second set of one or more electrodes against the leg such that they partially surround the back of the leg at a location 102 distal to the knee, a third substrate holds a third set of one or more electrodes against the leg such that they partially surround the back of the leg at a location 103 proximal to the knee, and a fourth substrate holds a fourth set of one or more electrodes against the leg such that they partially surround the front of the leg at a location 104 distal to the knee.

[0088] Each set of electrodes at locations 101 to 104 is preferably shaped as an open arc that conforms to the contour of the leg. This arc can be achieved using a flexible substrate on which a plurality of individual electrode elements are mounted, as described above in conjunction with Fig. 6A Alternatively, the arc may be implemented using a rigid substrate on which one or more electrode elements are mounted. When an open arc configuration is used with an electrode array, it is important to place the array in any given pair used on opposite aspects of the body part to ensure that the field penetrates the body, because if both arcs in a given electrode pair are placed on the same aspect of the body, then significant electric fields may occur only in superficial areas of the body.

[0089] In this embodiment, a first AC voltage is applied between an electrode group attached at position 101 and an electrode group attached at position 102, thereby generating an electric field having field lines extending in the general direction of dotted line 106. Subsequently, a second AC voltage is applied between an electrode group attached at position 103 and an electrode group attached at position 104, thereby generating an electric field having field lines extending in the general direction of dotted line 107. This configuration will cause the two electric fields to form an X shape through the joint. Although the directions (106, 107) of the two fields may not be perpendicular, the angle between these fields will be large enough to provide improved results with respect to unidirectional fields. Preferably, the frequency of the first AC voltage and the second AC voltage is between 100kHz and 500kHz. In some preferred embodiments, the frequency is between 125kHz and 250kHz. Preferably, in at least a portion of the target area, the intensity of the two electric fields is at least 1V / cm.

[0090] In alternative embodiments, the knee may be treated by combining a pair of longitudinal arrays located above and below the joint, with a pair of transverse arrays placed on the sides of the joint. In these embodiments, the longitudinal arrays may completely surround the leg (e.g., Figure 3D ) or may partially surround the legs (e.g., as described above in conjunction with FIG. 10 ).

[0091] Note that the same concepts described above in conjunction with FIG. 10 in the case of the knee can also be applied in the case of the elbow or other joints if appropriate changes are made to the relevant dimensions.

[0092] Note that in some cases (e.g. FIG. 3A to FIG. 3F embodiments), arrays are designed to completely surround the body part on which they are placed, and in other cases (e.g. FIG. 10A to FIG. 10B In the embodiment of the present invention, the arrays are designed as open arcs that do not completely surround the body part in which they are placed. However, in both array configurations, each of the arrays must be positioned at a different position along the longitudinal axis.

[0093] The TT field can be delivered by an electrode array that capacitively couples the electric field generated by the field generating device into the body. For example, the array design structure described in U.S. Patent 7,715,921 can be incorporated into the design of the longitudinal array. The electrode array can also be designed as a composite electrode including multiple ceramic elements that are designed to be positioned against the skin of the subject, as described in U.S. Patent 8,715,203.

[0094] In some embodiments, the array is designed as a set of ceramic disks with a high dielectric constant that are connected to the body via a thin conductive gel. The disks in each array are electrically interconnected via flexible wiring, and tape is placed over the disks so that the array adheres firmly to the subject's body. The components used to create the longitudinal array may be similar to those currently used to deliver TT fields to the head using OptuneTM, and to deliver TT fields to the torso using NovoTTF-10OL. The ceramic elements may be wired in parallel, in series, or any combination of parallel and series (e.g., 3 groups wired in parallel, each group including 3 disks wired in series).

[0095] Optionally, the design of the array layout may be performed with the aid of finite element simulations, which can be used to calculate the expected field distribution that will result from any particular design of longitudinal array. Such designs may be optimized to deliver maximum field strength to the target area.

[0096] Optionally, the disks in each array can be connected in a manner that enables them to fit subjects of different sizes. (For example, each array may include several connected patches with a small number of disks, or the disks may be connected with flexible connectors).

[0097] Although the above embodiments are described in the context of human subjects, they may also be used with other animals (eg, dogs, horses, etc.) with appropriate modifications, as will be apparent to those skilled in the relevant art.

[0098] Although the present invention has been disclosed with reference to certain embodiments, various modifications, variations and changes may be made to the described embodiments without departing from the scope and spirit of the invention as defined in the appended claims. Therefore, the present invention is not intended to be limited to the described embodiments, but has the full scope defined by the language of the appended claims and their equivalents.

Claims

1. An apparatus for treating a target area in a subject's body with a TT field, the target area being located in a portion of the subject's body having a longitudinal axis, the apparatus comprising an AC voltage generator, and further comprising: a first set of one or more capacitively coupled electrodes; a first strip substrate configured to hold the first set of one or more electrodes against the subject's body such that the first set of one or more electrodes encompasses a first portion of the subject's body at a location longitudinally anterior to the target area along a longitudinal axis; a second set of one or more capacitively coupled electrodes; a second strip substrate configured to hold the second set of one or more electrodes against the subject's body such that the second set of one or more electrodes encompasses a second portion of the subject's body at a location longitudinally posterior to the target area along the longitudinal axis; wiring configured to enable an AC signal generator to apply a voltage between all electrodes in the first set of one or more electrodes and all electrodes in the second set of one or more electrodes; a third set of one or more capacitively coupled electrodes; a third substrate configured to hold the third set of one or more electrodes against the body of the subject on a first side of the target area at a location longitudinally between the first set of one or more electrodes and the second set of one or more electrodes along the longitudinal axis; a fourth set of one or more capacitively coupled electrodes; a fourth substrate configured to hold the fourth set of one or more electrodes against the body of the subject on a second side of the target area opposite the first side at a location longitudinally between the first set of one or more electrodes and the second set of one or more electrodes along the longitudinal axis; as well as wiring configured to enable an AC signal generator to apply a voltage between all electrodes in the third set of one or more electrodes and all electrodes in the fourth set of one or more electrodes; wherein the AC voltage generator is configured to generate, in a repeating and alternating sequence, an AC voltage having a frequency of 100 kHz to 500 kHz between the first set of one or more electrodes and the second set of one or more electrodes, and an AC voltage having a frequency of 100 kHz to 500 kHz between the third set of one or more electrodes and the fourth set of one or more electrodes; wherein, when receiving an AC voltage, the first group of one or more electrodes and the second group of one or more electrodes form a first electric field, and the third group of one or more electrodes and the fourth group of one or more electrodes form a second electric field, and wherein the first electric field and the second electric field intersect each other along the longitudinal axis at a joint of an elbow of an arm or a knee of a leg; The individual electrode elements within each electrode group are wired together using appropriate wiring.

2. The device according to claim 1, wherein the AC voltage generator is configured to generate an AC voltage having a frequency of 125 kHz to 250 kHz between the first group of one or more electrodes and the second group of one or more electrodes, and an AC voltage having a frequency of 125 kHz to 250 kHz between the third group of one or more electrodes and the fourth group of one or more electrodes in a repeated and alternating sequence.

3. The apparatus of claim 1, wherein the first set of one or more electrodes comprises a first plurality of flat electrode elements and the second set of one or more electrodes comprises a second plurality of flat electrode elements. 4 . The device of claim 3 , wherein each of the first strip-shaped substrate and the second strip-shaped substrate is flexible.

5. The apparatus of claim 1, wherein each of the first and second belt-like substrates is shaped and sized to fit around a limb of the subject's body.

6. The apparatus according to claim 1, further comprising: a fifth set of one or more capacitively coupled electrodes; a fifth substrate configured to hold the fifth set of one or more electrodes against the body of the subject on a third side of the target area at a location longitudinally between the first set of one or more electrodes and the second set of one or more electrodes along the longitudinal axis; a sixth set of one or more capacitively coupled electrodes; as well as A sixth substrate is configured to hold the sixth group of one or more electrodes against the body of the subject on a fourth side of the target area opposite to the third side at a position longitudinally located between the first group of one or more electrodes and the second group of one or more electrodes along the longitudinal axis.

7. An apparatus for treating a target area in a subject's body with a TT field, the target area being located in a portion of the subject's body having a longitudinal axis, the apparatus comprising an AC voltage generator, and further comprising: a first set of one or more electrodes affixed to the subject's body so as to surround a first portion of the subject's body at a location longitudinally anterior to the target area along a longitudinal axis; a second set of one or more electrodes affixed to the subject's body so as to surround a second portion of the subject's body at a location longitudinally posterior to the target area along the longitudinal axis; as well as wiring configured to enable an AC signal generator to apply a voltage between all electrodes in the first set of one or more electrodes and all electrodes in the second set of one or more electrodes; a third set of one or more electrodes, longitudinally located along the longitudinal axis at a location between the first set of one or more electrodes and the second set of one or more electrodes, the third set of one or more electrodes being affixed to the subject's body on a first side of the target area; a fourth set of one or more electrodes, longitudinally located along the longitudinal axis at a position between the first set of one or more electrodes and the second set of one or more electrodes, the fourth set of one or more electrodes being attached to the subject's body on a second side of the target area opposite the first side; wiring configured to enable an AC signal generator to apply a voltage between all electrodes in the third set of one or more electrodes and all electrodes in the fourth set of one or more electrodes; wherein the AC voltage generator is configured to generate, in a repeating and alternating sequence, a first AC voltage having a frequency of 100 kHz to 500 kHz between the first set of one or more electrodes and the second set of one or more electrodes, and a second AC voltage having a frequency of 100 kHz to 500 kHz between the third set of one or more electrodes and the fourth set of one or more electrodes; wherein, when receiving an AC voltage, the first group of one or more electrodes and the second group of one or more electrodes form a first AC electric field, and the third group of one or more electrodes and the fourth group of one or more electrodes form a second AC electric field, and wherein the first AC electric field and the second AC electric field intersect each other along the longitudinal axis at a joint of an elbow of an arm or a knee of a leg, and the first AC electric field and the second AC electric field have a field strength of at least 1 V / cm in at least a portion of the target area; The individual electrode elements within each electrode group are wired together using appropriate wiring.

8. The apparatus of claim 7, wherein each of the first set of one or more electrodes and the second set of one or more electrodes is capacitively coupled to the subject's body.

9. The apparatus of claim 7, wherein each of the first set of one or more electrodes, the second set of one or more electrodes, the third set of one or more electrodes, and the fourth set of one or more electrodes are capacitively coupled to the subject's body. 10 . The apparatus of claim 9 , wherein each of the first AC voltage and the second AC voltage has a frequency of 125 kHz to 250 kHz. 11 . The device of claim 10 , wherein applying the first AC voltage and applying the second AC voltage are repeated at least 10,000 times in an alternating sequence.

12. The apparatus according to claim 7, further comprising: a fifth set of one or more electrodes, longitudinally located along the longitudinal axis at a location between the first set of one or more electrodes and the second set of one or more electrodes, the fifth set of one or more electrodes being attached to the subject's body on a third side of the target area; a sixth set of one or more electrodes, longitudinally located along the longitudinal axis at a position between the first set of one or more electrodes and the second set of one or more electrodes, the sixth set of one or more electrodes being attached to the subject's body on a fourth side of the target area opposite the third side; wherein the AC voltage generator is configured to generate a third AC voltage having a frequency of 100 kHz to 500 kHz between the fifth group of one or more electrodes and the sixth group of one or more electrodes in a repeated and alternating sequence so as to impose a third AC electric field through the target area, the third AC electric field having a field strength of at least 1 V / cm in at least a portion of the target area. 13 . The device of claim 12 , wherein applying the first AC voltage, applying the second AC voltage, and applying the third AC voltage are repeated at least 10,000 times in an alternating sequence.

14. The apparatus of claim 7, wherein the first set of one or more electrodes comprises a first plurality of flat electrode elements distributed around the first portion of the subject's body, and Wherein the second set of one or more electrodes comprises a second plurality of flat electrode elements distributed around the second portion of the subject's body.

15. A device according to claim 7, wherein the target area is located in a limb of the subject's body, wherein the longitudinal axis extends through the limb in a proximal to distal direction, wherein the first group of one or more electrodes are positioned around the limb at a location proximal to the target area, and wherein the second group of one or more electrodes are positioned around the limb at a location distal to the target area.

16. An apparatus for treating a target area in a limb of a subject's body with a TT field, the apparatus comprising an AC voltage generator, and further comprising: a first set of one or more capacitively coupled electrodes; a first substrate configured to hold the first set of one or more electrodes against a body of the subject such that the first set of one or more electrodes partially surrounds a first side of the limb at a location proximal to the target area; a second set of one or more capacitively coupled electrodes; a second substrate configured to hold the second set of one or more electrodes against the subject's body such that the second set of one or more electrodes partially surrounds a second side of the limb at a location distal to the target area, wherein the second side of the limb is opposite the first side of the limb; wiring configured to enable an AC signal generator to apply a voltage between all electrodes in the first set of one or more electrodes and all electrodes in the second set of one or more electrodes; a third set of one or more capacitively coupled electrodes; a third substrate configured to hold the third set of one or more electrodes against the subject's body such that the third set of one or more electrodes partially surrounds the second side of the limb at a location proximal to the target area; a fourth set of one or more capacitively coupled electrodes; a fourth substrate configured to hold the fourth set of one or more electrodes against the subject's body such that the fourth set of one or more electrodes partially surrounds the first side of the limb at a location distal to the target area; as well as wiring configured to enable an AC signal generator to apply a voltage between all electrodes in the third set of one or more electrodes and all electrodes in the fourth set of one or more electrodes; wherein the AC voltage generator is configured to generate, in a repeating and alternating sequence, a first AC voltage having a frequency of 100 kHz to 500 kHz between the first set of one or more electrodes and the second set of one or more electrodes, and a second AC voltage having a frequency of 100 kHz to 500 kHz between the third set of one or more electrodes and the fourth set of one or more electrodes; wherein, upon receiving an AC voltage, the first set of one or more electrodes and the second set of one or more electrodes form a first electric field, and the third set of one or more electrodes and the fourth set of one or more electrodes form a second electric field, and wherein the first electric field and the second electric field intersect each other to form an X-shape extending longitudinally through the target area; The individual electrode elements within each electrode group are wired together using appropriate wiring. 17 . The apparatus of claim 16 , wherein each of the first AC voltage and the second AC voltage has a frequency of 125 kHz to 250 kHz.

18. The device of claim 16, wherein each of the first set of one or more electrodes, the second set of one or more electrodes, the third set of one or more electrodes, and the fourth set of one or more electrodes comprises a plurality of flat electrode elements.

19. The device of claim 18, wherein each of the first substrate, the second substrate, the third substrate, and the fourth substrate is flexible.

20. The device of claim 16, wherein the limb is an arm having an elbow, wherein each of the first and third base plates is shaped and sized to fit proximally on the arm relative to the elbow, and Wherein each of the second base plate and the fourth base plate is shaped and sized to be mounted on the arm distally relative to the elbow.

21. The apparatus of claim 16, wherein the limb is a leg having a knee, wherein each of the first and third base plates is shaped and sized to fit proximally on the leg relative to the knee, and Wherein each of the second base plate and the fourth base plate is shaped and sized to be mounted on the leg distally relative to the knee.

22. An apparatus for treating a target area in a limb of a subject's body with a TT field, the apparatus comprising an AC voltage generator, and further comprising: a first set of one or more electrodes affixed so as to partially surround a first side of the limb at a location proximal to the target area; a second set of one or more electrodes affixed so as to partially surround a second side of the limb at a location distal to the target area, wherein the second side of the limb is opposite the first side of the limb; wiring configured to enable an AC signal generator to apply a voltage between all electrodes in the first set of one or more electrodes and all electrodes in the second set of one or more electrodes; a third set of one or more electrodes affixed so as to partially surround the second side of the limb at a location proximal to the target area; a fourth set of one or more electrodes affixed so as to partially surround the first side of the limb at a location distal to the target area; wiring configured to enable an AC signal generator to apply a voltage between all electrodes in the third set of one or more electrodes and all electrodes in the fourth set of one or more electrodes; as well as wherein the AC voltage generator is configured to generate, in a repeating and alternating sequence, a first AC voltage having a frequency of 100 kHz to 500 kHz between the first set of one or more electrodes and the second set of one or more electrodes so as to impose a first AC electric field through the target area, the first AC electric field having a field strength of at least 1 V / cm in at least a portion of the target area, and a second AC voltage having a frequency of 100 kHz to 500 kHz between the third set of one or more electrodes and the fourth set of one or more electrodes so as to impose a second AC electric field through the target area, the second AC electric field having a field strength of at least 1 V / cm in at least a portion of the target area, wherein applying the first AC voltage and applying the second AC voltage are performed in a repeated and alternating sequence, and wherein, upon receiving the AC voltages, the first group of one or more electrodes and the second group of one or more electrodes form a first AC electric field, and the third group of one or more electrodes and the fourth group of one or more electrodes form a second AC electric field, and wherein the first AC electric field and the second AC electric field intersect each other to form an X-shape extending longitudinally through the target area; The individual electrode elements within each electrode group are wired together using appropriate wiring.

23. The apparatus of claim 22, wherein each of the first set of one or more electrodes, the second set of one or more electrodes, the third set of one or more electrodes, and the fourth set of one or more electrodes are capacitively coupled to the subject's body.

24. The apparatus of claim 23, wherein each of the first AC voltage and the second AC voltage has a frequency of 125 kHz to 250 kHz.

25. The apparatus of claim 22, wherein applying the first AC voltage and applying the second AC voltage are repeated at least 10,000 times in an alternating sequence.

26. The device of claim 22, wherein the limb is an arm having an elbow, wherein the first set of one or more electrodes and the third set of one or more electrodes are positioned proximally relative to the elbow, and wherein the second set of one or more electrodes and the fourth set of one or more electrodes are positioned distally relative to the elbow.

27. The device of claim 22, wherein the limb is a leg having a knee, wherein the first group of one or more electrodes and the third group of one or more electrodes are positioned proximally relative to the knee, and wherein the second group of one or more electrodes and the fourth group of one or more electrodes are positioned distally relative to the knee.

28. The device of claim 22, wherein each of the first set of one or more electrodes, the second set of one or more electrodes, the third set of one or more electrodes, and the fourth set of one or more electrodes comprises a plurality of flat electrode elements.

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