Treatment assembly for providing a tumor treatment electric field to an animal test subject - Patents.com

Abstract

The treatment assembly may have an inner layer having an inner surface and an outer surface and defining a plurality of openings extending therethrough. The treatment assembly may further include a plurality of plates each at least partially received within a respective one of the plurality of openings in the inner layer. The treatment assembly may further include a treatment circuit including a cable having a plurality of electrical leads and a plurality of lead ends, each electrical lead electrically connected to a respective one of the plurality of lead ends. A cover layer may be attached to the outer surface of the inner layer and cover the plurality of lead ends of the cable. The plurality of lead ends may contact respective ones of the plurality of plates to define a plurality of electrodes.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to and benefit of the filing dates of U.S. Provisional Patent Application No. 62 / 951,605, filed December 20, 2019, and U.S. Provisional Patent Application No. 63 / 104,788, filed October 23, 2020, the entireties of each of which are incorporated by reference herein.

[0002] The present disclosure relates to systems, devices, and methods for testing and using Tumor Treating Electric Fields (TTFields). The disclosure includes a description of a cage assembly, treatment assembly, and swivel system for use with animal test subjects. [Background technology]

[0003] Tumor Treating Fields, or TTFields, are low intensity (e.g., 1 V / cm-3 V / cm) alternating electric fields in the mid-frequency range (100 kHz-300 kHz). This non-invasive treatment is targeted to solid tumors and is described in U.S. Patent No. 5,399,633, which is incorporated herein by reference in its entirety. TTFields disrupt cell division through physical interactions with key molecules during mitosis. TTFields therapy is an approved mononucleosis treatment for recurrent glioblastoma and an approved combination therapy with chemotherapy for newly diagnosed patients. These electric fields are induced non-invasively by a transducer array (i.e., an array of electrodes) placed directly on the patient's scalp. TTFields may also be beneficial for treating tumors in other parts of the body. Laboratory studies have begun to test mid-frequency alternating electric fields (Tumor Treating Fields, or TTFields) on subcutaneous and orthotropic tumors located on the torso of small animals (e.g., mice). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] U.S. Patent No. 7,565,205 Summary of the Invention [Means for solving the problem]

[0005] In various aspects, described herein is a treatment assembly comprising an inner layer having an inner surface and an outer surface. Optionally, the treatment assembly can be placed on an animal test subject, and the animal test subject can optionally receive the TTFields or a control treatment. The inner layer can define a plurality of apertures extending therethrough. The treatment assembly can further comprise a plurality of plates each at least partially received within a respective opening of the plurality of apertures of the inner layer. The treatment assembly can further comprise a treatment circuit comprising a cable having a plurality of electrical leads and a plurality of lead ends, each electrical lead electrically connected to a respective lead end of the plurality of lead ends. A cover layer can be attached to the outer surface of the inner layer and cover the plurality of lead ends of the cable. The plurality of lead ends can contact a respective plate of the plurality of plates to define a plurality of electrodes, each electrode of the plurality of electrodes comprising a respective lead end and a respective plate.

[0006] At least one plate of the plurality of plates may comprise a ceramic plate.

[0007] At least one of the plurality of plates may comprise a glass plate.

[0008] At least one electrode of the plurality of electrodes can be configured to generate an electric field through a corresponding plate of the plurality of plates.

[0009] The electrodes of the treatment circuit may have respective upper surfaces, and the cover layer may extend over the upper surfaces of the electrodes of the cable.

[0010] Each plate of the plurality of plates may have a lower surface and an opposite upper surface. The treatment assembly may further comprise a layer of hydrogel on the lower surface of each plate of the plurality of plates.

[0011] The therapy circuit may further include at least one temperature sensor.

[0012] The inner layer and the cover layer may cooperate to define a hole through the treatment assembly. The hole may be configured to receive a subcutaneous tumor therethrough.

[0013] The treatment assembly may further comprise a cap extending across the aperture and defining a receiving portion therein configured to receive the subcutaneous tumor. The cap may be attached to the cover layer.

[0014] The multiple plates may be positioned radially outwardly of a hole defined through the treatment assembly.

[0015] The cap may include a rim. The treatment assembly may further include an adhesive ring that covers the rim and secures the cap to the cover layer.

[0016] The treatment assembly may have a longitudinal dimension in a pre-use configuration. The cover layer may include a biocompatible non-woven adhesive. The non-woven adhesive may be elastic in the longitudinal dimension.

[0017] In the use configuration, the cables may extend perpendicular or substantially perpendicular to the longitudinal dimension.

[0018] The inner layer may include a biocompatible, breathable polyurethane adhesive on an inner surface of the inner layer.

[0019] The cover layer may have an inner surface that includes a biocompatible non-woven adhesive.

[0020] The plurality of electrodes may comprise a plurality of electric field generating electrodes configured to transmit an electric field through a corresponding plate of the plurality of plates.

[0021] The therapy circuit may further comprise a plurality of thermistors.

[0022] A respective electrode of the plurality of electrodes and a respective thermistor of the plurality of thermistors may be in communication with each plate of the plurality of plates.

[0023] The treatment assembly may weigh less than 2.5 grams.

[0024] The treatment assembly may be flexible enough to circumferentially conform to a portion of the torso of the animal subject.

[0025] The cable may include an end connector disposed at an end of the cable opposite the plurality of electrodes, The end connector may be configured to allow connection of the cable to an electrical signal generating device.

[0026] The treatment assembly may further comprise a release layer in contact with the biocompatible, breathable polyurethane adhesive on the inner surface of the inner layer.

[0027] The release layer can have a shape that is complementary to the shape of the cover layer.

[0028] The cover layer may define at least one tab portion extending beyond the inner layer.

[0029] The at least one tab portion may include two opposing tab portions that are complementary to one another when the cover layer defines a circumferential hoop.

[0030] The plurality of apertures may comprise a plurality of longitudinally spaced apertures.

[0031] The therapy circuit and cable may be constructed together as a flexible printed circuit board.

[0032] A method of making a treatment assembly may include disposing a plurality of plates into respective openings in an inner layer of the treatment assembly, disposing each electrode of a plurality of electrodes of a treatment circuit in contact with a plate of the plurality of plates, and attaching a cover layer to an outer surface of the inner layer, the cover layer may cover the plurality of electrodes of the treatment circuit.

[0033] The method may further include applying a layer of hydrogel to an underside of each plate of the plurality of plates.

[0034] The lower surfaces of at least two of the plurality of plates may share a layer of hydrogel.

[0035] The method may include electrically coupling at least a portion of the electrodes of the treatment assembly to an electrical signal generator and attaching the treatment assembly to an animal subject having a tumor. The plates of the treatment assembly may surround at least a portion of the tumor. The electrical signal generator may be used to generate an electrical signal (e.g., an electrical potential). At least a portion of the electrodes of the treatment assembly may be used to deliver an electrical signal through a corresponding plate of the plurality of plates, thereby generating an electric field.

[0036] The tumor can be an organ tumor. In a pre-use configuration, the plurality of openings and the plurality of plates can be spaced longitudinally along a longitudinal axis of the treatment assembly. In a use configuration, the plurality of openings and the plurality of plates can be spaced circumferentially around the torso of the animal subject to surround the organ tumor.

[0037] The tumor can be a subcutaneous tumor. The plurality of openings can be radially spaced from a hole extending through the treatment assembly. The hole can receive at least a portion of the subcutaneous tumor.

[0038] The method may further include the steps of placing a cap over the subcutaneous tumor and securing the cap to a cover layer of the treatment assembly.

[0039] Using the electrical signal generator to generate the electrical signal may include sequentially generating a first electrical signal and a second electrical signal. Using at least a portion of the electrodes of the treatment assembly to generate an electric field from the electrical signal may include using a first electrode and a second electrode to generate a first electric field across the tumor from the first electrical signal, and using a third electrode and a fourth electrode to generate a second electric field across the tumor from the second electrical signal.

[0040] The first electric field and the second electric field may each have an axis of propagation, and the axis of propagation of the first electric field may intersect the axis of propagation of the second electric field.

[0041] Using an electrical signal generator to generate an electrical signal may include generating an electrical signal at a frequency between 50 kHz and 500 kHz. The electrical signal may correspond to an alternating current provided at a frequency between 50 kHz and 500 kHz (or 150 kHz-300 kHz, or at or near 200 kHz) configured to generate TTFields as further discussed herein.

[0042] The animal subject may be a member of the experimental group. The method may further include electrically coupling at least a portion of the electrodes of the control heating device to the electrical signal generator. The control heating device may be attached to a second animal subject having a tumor. The second animal subject may be a member of the control group. The heater of the second treatment assembly may surround at least a portion of the tumor. The electrical signal generator may be used to generate heat through the heater of the control heating device. At least a portion of the electrodes of the second treatment assembly may conduct heat through a corresponding plate of the plurality of plates. The heat generated by the control heating device may mimic the heat generated by the first treatment assembly during delivery of the electric field.

[0043] The control heating device may include a circuit having a plurality of zones arranged in a spaced apart configuration matching the configuration of the plurality of electrodes of the treatment assembly, at least one heater disposed in each of the plurality of zones, at least one temperature sensor, and a cable in communication with the at least one heater and the at least one temperature sensor of the circuit.

[0044] The at least one temperature sensor may comprise a plurality of temperature sensors, each temperature sensor of the plurality of temperature sensors disposed in a respective one of the plurality of zones.

[0045] The circuitry and cable may be constructed together as a flexible printed circuit board.

[0046] The control heating device may further include an inner layer having an upper surface and including a plurality of openings, and a cover layer extending across the upper surface of the inner layer. Each of the zones may be disposed within an opening of the plurality of openings.

[0047] Additional advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by the practice of the invention. The advantages of the invention will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention as claimed.

[0048] These and other features of the preferred embodiments of the present invention will become more apparent in the following detailed description, in which reference is made to the accompanying drawings. [Brief description of the drawings]

[0049] [Figure 1] FIG. 1 is a diagram of a system for testing TTFields therapy according to embodiments disclosed herein. [Diagram 2] FIG. 1 is a diagram of a test subject having a treatment assembly attached thereto. [Diagram 3] FIG. 1 is an exploded view of a cage system according to an embodiment of the present disclosure. [Figure 4] FIG. 4 is a front view of the cage system of FIG. 3. [Diagram 5] FIG. 4 is a side view of the cage system of FIG. 3. [Figure 6] 6 is a schematic diagram of a test subject within the interior of the cage system of FIG. 3 , approximating a cross-section taken at plane P of FIG. 5 . [Figure 7] FIG. 4 is a schematic diagram showing measurements inside the enclosure of the cage system of FIG. 3. [Figure 8] FIG. 2 is an exploded view of a treatment assembly according to an embodiment disclosed herein for use with a system such as in FIG. 1. [Figure 9] 2 is an exploded view of another treatment assembly according to an embodiment disclosed herein for use with a system such as in FIG. 1. [Figure 10A] FIG. 2 is an exploded view of a control heater assembly according to embodiments disclosed herein. [Figure 10B] FIG. 10B is a diagram of a portion of a circuit board of the control heater assembly of FIG. 10A. [Figure 11A] FIG. 13 is an exploded view of another control heater assembly according to embodiments disclosed herein. [Figure 11B] FIG. 11B is a diagram of a portion of a circuit board of the control heater assembly of FIG. [Figure 12A] FIG. 13 is a partial exploded view of a cage showing the placement of a swivel relative to an associated cage assembly according to an embodiment disclosed herein. [Figure 12B] FIG. 12B is a detailed view of the pivot portion of FIG. 12A. [Figure 13] FIG. 12C is a side view of the circuit board of the pivot assembly of FIG. 12B. [Figure 14] FIG. 14 is a perspective view of the circuit board of FIG. 13 showing the internal circuitry. [Figure 15] FIG. 12C is an exploded view of the pivot portion of FIG. 12B. [Figure 16] FIG. 12C is a side view of the pivot portion of FIG. 12B. [Figure 17] FIG. 12C is a bottom view of the swivel portion of FIG. 12B. [Figure 18A] FIG. 12C is a perspective view of the pivot portion of FIG. 12B. [Figure 18B] FIG. 18B is a detailed perspective view of a portion of the pivot of FIG. 18A showing the torque sensor assembly with the pivot in a neutral position. [Figure 19] FIG. 18C is a perspective view of a portion of the swivel as in FIG. 18B, showing the pivot body being rotated from a neutral position. [Figure 20] FIG. 1 is a schematic diagram of a treatment assembly according to an embodiment disclosed herein for providing treatment to an organ tumor. [Figure 21] FIG. 1 is a schematic diagram of a treatment assembly according to an embodiment disclosed herein for providing treatment to a subcutaneous tumor. [Figure 22] FIG. 2 is a schematic diagram of a computing device for use with the system of FIG. 1. [Diagram 23] FIG. 13 is an exploded view of an embodiment of a swivel and its housing. [Figure 24] FIG. 2 is an exploded view of an exemplary treatment assembly. [Diagram 25] FIG. 25 is a top view of an exemplary treatment assembly as in FIG. 24. [Figure 26] FIG. 25 is a perspective view of the treatment assembly of FIG. 24 positioned on a test subject. [Figure 27] FIG. 25 is a top view of the treatment assembly of FIG. 24 positioned on a test subject. [Figure 28] FIG. 25 is a top view of the treatment assembly of FIG. 24 showing communication between the electrodes. [Figure 29] FIG. 25 is a top view of the treatment assembly of FIG. 24 showing the alternating shaped portions. [Diagram 30] FIG. 2 is a side view of an annulus according to embodiments disclosed herein. [Diagram 31] FIG. 31 is a side view of the annulus of FIG. 30. [Diagram 32] FIG. 31 is a top view of the annulus of FIG. 30. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0050] The present invention will now be described more fully hereinafter with reference to the accompanying drawings, in which some, but not all, embodiments of the invention are shown. Indeed, the present invention may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein, but rather these embodiments are provided so that this disclosure will satisfy applicable legal requirements. Like reference characters refer to like elements throughout. It is understood that the present invention is not limited to the specific methodologies and procedures described, as such may vary. It is also understood that the terminology used herein is for the purpose of describing specific embodiments only, and is not intended to limit the scope of the present invention.

[0051] Many modifications and other embodiments of the inventions set forth herein will occur to one skilled in the art to which the inventions pertain having the benefit of the teachings presented in the foregoing descriptions and the associated drawings. It is to be understood, therefore, that the invention is not limited to the specific embodiments disclosed, and that modifications and other embodiments are intended to be included within the scope of the appended claims. Although specific terms have been employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation.

[0052] As used herein, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. For example, use of the term "an electrode" can refer to one or more of such electrodes.

[0053] All technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs, unless clearly indicated otherwise.

[0054] As used herein, the term "optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where said event or circumstance occurs and instances where said event or circumstance does not occur.

[0055] As used herein, the term "at least one of" is intended to be synonymous with "one or more of." For example, "at least one of A, B, and C" explicitly includes A alone, B alone, C alone, and combinations of each.

[0056] Ranges may be expressed herein as from "about" a particular value and / or to "about" another particular value. When such a range is expressed, other aspects include from the particular value and / or to the other particular value. Similarly, when values ​​are expressed as approximations, it is to be understood that by use of the antecedent "about," the particular value forms another aspect. It is further to be understood that each endpoint of the range is significant both in relation to the other endpoint and independently of the other endpoint. Optionally, in certain aspects, when values ​​are approximated by use of the antecedent "about," it is contemplated that values ​​within up to 15%, up to 10%, up to 5%, or up to 1% (above or below) of the specific stated value may fall within the scope of those aspects. Similarly, the use of "substantially" (e.g., "substantially parallel") or "generally" (e.g., "generally planar") should be understood to include embodiments where the angle is within about 10 degrees, 5 degrees, or 1 degree.

[0057] As used herein, the word "or" means any one element of a particular list and also includes any combination of elements of that list.

[0058] Unless expressly stated otherwise, it is not intended that the methods described herein be construed as requiring that the steps of the method be performed in a particular order. Thus, where a method claim does not actually suggest the order in which its steps occur sequentially, or where it is not otherwise expressly stated in the claim or description that the steps are limited to a particular order, no order is intended to be inferred in any respect. This preserves possible non-expressive bases for interpretation, including questions of theory regarding the sequence of steps or flow of operations, the apparent meaning derived from grammatical constructions or punctuation, and the number or type of aspects described in the specification.

[0059] In the following description and claims, when the words "comprising" or "including" are used, the words "comprising" or "including" can be optionally replaced with the words "consisting essentially of" or "consisting of" to form alternative embodiments.

[0060] The following description provides specific details to provide a thorough understanding. Nonetheless, those skilled in the art will understand that the devices, systems, and related methods using the devices can be implemented and used without these specific details. In fact, the devices, systems, and related methods can be implemented by modifying the illustrated devices, systems, and related methods, and can be used in conjunction with any other devices and techniques conventionally used in the industry.

[0061] TTFields, also referred to herein as alternating electric fields, have been established as an antimitotic cancer treatment because they interfere with proper microtubule assembly during metaphase, ultimately destroying cells during telophase and cytokinesis. Efficacy increases with increasing electric field strength, with the optimal frequency dependent cancer cell lines at 200 kHz, the frequency at which inhibition of glioma cell growth caused by TTFields is highest. For cancer treatment, non-invasive devices have been developed with capacitively coupled transducers placed directly in skin areas close to the tumor. For patients with glioblastoma multiforme (GBM), the most common and fundamental malignant brain tumor in humans, a system for delivering TTFields therapy is called the OPTUNE™ System (Novocure Ltd.).

[0062] Because the effect of TTFields is more directional with cells dividing parallel to the electric field than with cells dividing in other directions, and because cells divide in all directions, TTFields are typically delivered through two pairs of transducer arrays that generate a perpendicular electric field within the tumor being treated. More specifically, for the OPTUNE system, one pair of electrodes is positioned on the left-right (LR) side of the tumor, and the other pair of electrodes is positioned on the anterior-posterior (AP) side of the tumor. Cycling the electric field between these two directions (i.e., LR and AP) ensures that the maximum range of cell orientations is targeted.

[0063] While TTFields have been approved for use in certain patients, there is a need for a system that allows for reliable, consistent, and safe testing of TTFields in animal test subjects. In small animal (e.g., mouse) studies where electrical components are coupled to the animal, the animal often chews or damages the electrical components. Also, when the animal is tethered using a cable, the animal often causes the cable to twist. If excessive slack is provided in such cables, the animal can easily roll around, resulting in damage or improper placement of the electrical components. If sufficient slack is not provided in such cables, the animal's movement can be overly restricted. Additionally, it can be difficult to couple the electrical components to the animal without significant adjustment and repositioning.

[0064] In various embodiments, and with reference to FIG. 1 , disclosed herein is a system 10 for providing TTFields to a test subject 12 (e.g., an animal test subject, such as a mouse). The system 10 may include one or more cage assemblies 100 for receiving and housing one or more test subjects. Some test subjects in the experimental group 14 may be fitted with TTFields treatment assemblies 200, 200′, 200″ (FIGS. 8, 9, and 24), which may include a transducer array for providing treatment to the test subjects. Other test subjects in the control group 16 may be fitted with control heater treatment assemblies 400, 400′ (FIGS. 10A-11B), which are configured to provide the same weight and heat as the TTFields treatment assemblies 200, 200′, 200″. The multiple TTFields treatment assemblies 200, 200', 200" can be communicatively coupled to a TTFields generating device 18. Optionally, the TTFields generating device can be a generator provided as part of an INOVITRO laboratory research system (NOVOCURE GMBH). Similarly, the multiple control heater treatment assemblies 400 can be communicatively coupled to the same or a separate TTFields generating device 18 (or other generator capable of initiating heat through the control heater treatment assembly as further disclosed herein). A computer 1001 can be communicatively coupled to the TTFields generating device 18. The computer 1001 can control the output of the TTFields generating device 18, the treatment assemblies 200, 200', 200", the control heater treatment assembly 400, and / or log data from the test subject 12.

[0065] The TTFields treatment assemblies 200, 200', 200" and control heater treatment assembly 400 can communicate with the TTFields generation device 18 via respective cables 204 (FIG. 8). To allow the test subject to move freely within the cage assembly 100 without wrapping the cables 204, the cables 204 can extend to and be coupled to a swivel section 300 (also referred to interchangeably herein as the swivel assembly 300). The swivel section 300 can further extend to and be coupled to a second cable 20 that connects to the TTFields generation device 18. Thus, as further disclosed herein, the swivel section 300 can enable electrical communication from the TTFields generation device 18 through the second cable 20, through the swivel assembly 300 to the cable 204 for communication with the treatment assemblies 200, 200', 200" while inhibiting wrapping of the cables 204.

[0066] Cage Assembly 3-5, the cage assembly 100 may include a main body 102. The main body 102 may include a floor 104 defining a floor area having a major dimension. Optionally, the floor 104 may be rectangular or roughly rectangular with corners 16. Optionally, the corners 16 may be rounded. The corners may have a radius of, for example, about 17 mm. The major dimension may be the largest diagonal between the corners 106 of the cage. The main body 102 may further include one or more side walls 108. For example, the main body 102 may include a front side wall 108A, an opposing rear side wall 108B, and a pair of side walls 108C extending between respective edges of the front side wall 108A and the rear side wall 108B. The intersections between the respective side walls may define rounded corners 110. Optionally, the side walls 108 may converge (i.e., slope inwardly downward) in a direction toward the floor 104 to provide a draft angle to allow for manufacture via injection molding. Optionally, the floor may include padding as commonly used in conventional animal cages. The padding may be, for example, sawdust. Food pellets may be placed on the floor of the enclosure for feeding. A conventional water bottle may be attached to the cage to provide water to the test subject. Optionally, the cage may include an opening in each enclosure side wall to receive a dispensing portion of a conventional water bottle.

[0067] In an exemplary embodiment, as shown in FIG. 3, the sidewall 108 may define multiple openings 130 for ventilation. One or more filters 132 may optionally cover the multiple openings in each sidewall 108. A frame 134 may extend around the periphery of the filters 132 and receive fasteners (e.g., nuts 136 and bolts 138) for attachment to the main body 102 of the cage assembly 100. In this manner, the cage assembly is sealed such that all or substantially all ventilation air to each enclosure passes through at least one filter before entering the ventilation opening. Optionally, as shown in FIG. 3, a single filter 132 may cover the multiple openings 130 (optionally all openings) in the sidewall 108. The filter may be removable, autoclavable, and replaceable. The filter may minimize the ingress of infectious materials and agents while allowing rapid air exchange. It is contemplated that a mesh, sieve, grid, air permeable membrane, or other permeable structure may be placed between the multiple openings 130 in the cage and the filter 132 to prevent the test subject from biting the filter.

[0068] 3, a door 112 may be pivotally connected to the main body portion 102 by a pair of hinges 114. In use, the door 112 may be movable between and about (1) a closed position, in which the door 112 cooperates with the side walls to provide an enclosure, and (2) an open position, in which the door is pivoted away from the interior of the cage assembly to provide one or more openings through which the interior of the cage assembly can be accessed.

[0069] A cover 120 may extend over the top of the main body 102. The cover 120 may be releasably attached to the main body 102 via a latch portion 122. The latch portion 122 may be pivotally attached to the main body 102 via a hinge 124. A latch portion 126, which is pivotable about a hinge 128, may be attached to the door 112. The latch portion 126 may be releasably engaged with a catch portion at the top of the cover 120 to hold the door 112 in a closed position. Optionally, the cover 120 may include one or more pivot housings 180 configured to receive at least a portion of a pivot as further disclosed herein.

[0070] A divider 140 may define a common side wall that divides the interior of the cage into a first enclosure 142 and a second enclosure 144. The divider 140 may optionally be removable. The main body may optionally define a slot into which the divider 140 may be inserted. The divider 140 may define an opening 146 (optionally multiple openings) between the first enclosure 142 and the second enclosure 144 to allow the respective test subjects 12 in each of the first and second enclosures to interact with one another (e.g., through vocal interaction, through odor, through body warmth, etc.). Thus, the first enclosure 142 and the second enclosure 144 may each have a respective sidewall (or sidewall portion) defined by a front wall 108A, a door 112, a rear wall 108B, a sidewall 108C extending between the front and rear walls, and a divider 140. In these examples, it is contemplated that the floor area within each enclosure may have a respective major dimension that may be equal to the largest diagonal between the corners of the enclosures.

[0071] The side walls (e.g., main body 102 and divider 140) and cover may optionally comprise polycarbonate and may optionally be autoclavable. Portions of the cage, such as main body 102 and cover 120, may be transparent to allow observation of a test subject confined in the cage.

[0072] With reference to FIG. 6, a shelter subassembly 150 may extend inwardly from the divider 140 into each of the first and second enclosures 142 and 144. Within each enclosure, the shelter subassembly 150 may include an arched roof, a pair of parallel walls extending vertically downward from the arched roof, and optionally a floor covering extending between the bottom edges of the side walls of the shelter subassembly. Within each enclosure, the shelter subassembly 150 may protrude a selected distance D from the divider 140. Optionally, the distance D may be about 4-5 centimeters. It is contemplated that the distance D may be selected such that the cable does not restrict the test subject from interacting with the test subject in the opposing enclosure. For example, the cable may be strapped to the back of the test subject at a selected distance d from the subject's head. In this manner, the test subject cannot bite the cable. This selected spacing may also allow the test subject to enter the shelter subassembly before the cable touches the shelter subassembly. Additionally, the cable may be flexible enough to bend when it touches the shelter subassembly. The selected distance that the shelter subassembly 150 protrudes from the partition 140 may be selected such that when the cable is fully pulled against the shelter subassembly, the test subject (e.g., at least the nose and / or face of the test subject) can at least reach the plane defined by the partition 140. As further disclosed herein, the cable length may be a function of the dimensions of the enclosure. Thus, the selected distance D that the shelter subassembly 150 protrudes from the partition 140 may be a function of the length of the cable, the height dimension of the enclosure, and the width dimension of the enclosure.

[0073] The cover 120 for the first enclosure and the cover 120 for the second enclosure may be integrally constructed as a cover assembly 178. Optionally, the cover assembly 178 may include a swivel housing 180. In these embodiments, the cover assembly 178 may further include a swivel 300 as further disclosed herein, the swivel being disposed within the respective swivel housing 180. The cover assembly 178 may include first and second openings between the first and second enclosures and their respective swivels 300. The first and second openings may provide communication by which a cable of the treatment assembly may be coupled to the respective swivels. The respective swivels may be in overlying relationship to each of the first and second openings. According to various embodiments, each swivel may extend at least partially through a respective opening in the cover assembly into a respective enclosure to receive a respective cable. In a further embodiment, each cable may extend through each of the first and second openings for coupling to a respective pivot.

[0074] 4-7, the distance between the cover 120 and the floor 104 can define the cage height. To prevent the test subject from having enough slack in the cable 204 to tip over or get tangled with the cable, the cage assembly can have a selected cage height h, i.e., a function of the length R1 and width R2, of each enclosure. For example, the cable 204 can have a selected length to prevent providing enough slack for the test subject to wrap the cable around the test subject's body. According to some optional embodiments, the dimensions of each enclosure 142, 144 can be selected to allow the test subject access to the corners of the cage, but when the test subject is positioned directly under the attachment of the cable to the swivel 300, the cable does not have enough slack to hang down or extend down the test subject's back and touch the cage floor. To maximize the usable area for a given cage height, the cable can extend from just above the center of the floor space of each enclosure. Thus, the height of the cage may be selected as a function of the major dimensions of the cage floor (for a given enclosure) and the height of the test subject. For example, the height may be selected based on the following equation: h≧(R1 2 +R2 2 -16a 2 ) / 16a where h is the cage height, R1 is the enclosure length, R2 is the enclosure width, and a is the animal height. Therefore, the height can be a function of the major dimension Y of the cage floor according to the following equation: h≧(Y 2 -16a 2 ) / 16a A typical test subject mouse may have a height (a) of 20 mm. Thus, in one example, the cage height h, in millimeters, can be a function of the major dimension Y of the cage floor (in millimeters) according to the following equation: h≧(Y 2 -6400) / 320[mm]

[0075] More generally, the height of the cage may be selected as a factor multiplied by the major dimension of the cage floor (of the respective enclosure). According to certain embodiments, the cage may have a height of at least 0.5 times the major dimension of the cage floor, at least 0.6 times the major dimension of the cage floor, at least 0.7 times the major dimension of the cage floor, at least 0.8 times the major dimension of the cage floor, at least 1.1 times the major dimension of the cage floor, or at least 1.2 times the major dimension of the cage floor.

[0076] In one exemplary embodiment, the cage assembly floor may have a length of about 315 mm and a width of about 185 mm. Thus, with a partition dividing the length of the floor, each enclosure may have a floor with a long side of 185 mm and a short side of 157 mm. Thus, the floor area of ​​each enclosure may have a major dimension of 242 cm (equal to the largest diagonal between the corners of the enclosure). Thus, it is contemplated that the cage height has a minimum height of at least 163 mm, providing a height that is about 0.7 times the major dimension of the cage floor. According to various aspects, the floor area of ​​each enclosure may have a minimum major dimension of at least 160 mm, between about 160 mm and about 200 mm, between about 200 mm and about 250 mm, between about 250 mm and about 300 mm, between about 300 mm and about 400 mm, or greater than about 400 mm. In one embodiment, the cage height may be about 260 mm. In further embodiments, the height of the cage may be at least 60 mm, at least 105 mm, at least 175 mm, at least 261 mm, or at least 480 mm.

[0077] It is contemplated that the above equation for selecting the cage height is not absolute, since the cable has some amount of stiffness (i.e., the cable has a limit to its flexibility), thereby limiting the cable's ability to reach the cage floor. Thus, it is contemplated that the cage height can be less than the minimum height in the above equation, while still providing a cage height sufficient to prevent entanglement of the test subject.

[0078] Optionally, the cage may include a feeder (e.g., a food tray or food dispenser), which may optionally be coupled to the divider 140 or other side wall so that it remains suspended.

[0079] treatment assembly With reference to FIG. 8 , a treatment assembly 200 may be configured to provide TTFields to an organ tumor. The treatment assembly 200 may include a flexible circuit board 202 including a connector end 206 and one or more lead ends 208 at the end of each electrical lead 205 opposite the connector end 206. The electrical leads 205 may be provided as components of a cable 204. Optionally, the flexible circuit board 202 may be configured to couple to a swivel 300. The cable 204 may be elongated and flexible enough to allow for a certain amount of twisting without the need for a swivel. The connector end 206 may optionally be a USB-C connector (e.g., a male USB-C connector). It is contemplated that the use of a flexible circuit board 202 as disclosed herein provides multiple electrical leads 205 as part of an integrated structure, thereby avoiding tangling of cables or wires and minimizing the space occupied by the electrical leads. Thus, in one embodiment, the cable 204 may be defined by a portion of the flexible circuit board 202 .

[0080] In a pre-use configuration, the lead ends 208 may be spaced apart along the longitudinal dimension 201 of the treatment assembly 200, as shown in FIG. 8. Optionally, the lead ends 208 may be arranged in one or more longitudinally extending rows. For example, the lead ends 208 may be arranged in two rows of four lead ends, with the two rows extending in the longitudinal dimension 201. As another example, the one or more longitudinally extending rows may comprise a single row of lead ends 208. However, it is contemplated that any desired arrangement of lead ends may be used. The cable 204 may extend perpendicular or substantially perpendicular to the longitudinal dimension 201.

[0081] Each lead end 208 may be configured to engage or couple with a respective plate 210. Thus, the treatment assembly 200 may include a plurality of electrodes, each electrode including a lead end 208 in contact with or coupled to a respective plate 210. In certain potential embodiments, at least one (optionally each) plate 210 may be a ceramic plate. In other embodiments, such as those in which the treatment assembly 200 functions as a control heating device, it is contemplated that at least one (optionally each) plate may be a glass plate. In still further aspects, other types of electrodes are contemplated, such as electrodes formed from metal or other conductive materials.

[0082] The treatment assembly 200 may include an inner layer 212 having an outer surface 214 and an inner surface 216. The inner layer 212 may include a biocompatible, breathable adhesive, such as polyurethane. In an embodiment, the inner layer may include a VANCIVE MED 9598A polyurethane film with an acrylic adhesive. The inner layer 212 may define a plurality of openings 218 therethrough for receiving the respective plates 210. The openings 218 may be spaced longitudinally along the inner layer. Although depicted as receiving an individual plate, it is contemplated that each opening may optionally receive multiple plates (e.g., two plates).

[0083] The plate 210 may have an upper surface 220 and a lower surface 222. The upper surface may be placed against the lead end 208. A layer of hydrogel 224 may be placed against the lower surface 222 of each of the plates 210. The layer of hydrogel 224 may optionally cover at least two adjacent plates 210. Optionally, the layer of hydrogel 224 may cover the lower surface 222 of the plate 210 and an adjacent portion of the inner surface of the inner layer 212. The layer of hydrogel 224 may be about 0.6 mm thick in one optional embodiment. The hydrogel 224 may include, for example, AG625 Sensitive Gel made by AXELGAARD.

[0084] A cover layer 230 can be attached to the outer surface 214 of the inner layer 212. The cover layer 230 can cover the multiple lead ends 208 of the flexible circuit board 202. The cover layer 230 can include one or more tab portions that extend beyond the periphery of the inner layer 212. For example, the cover layer 230 can include two opposing tab portions 232 that are complementary to each other when the cover layer defines a circumferential hoop (e.g., when wrapped around the torso of a test subject, as further disclosed herein). Optionally, the tab portions 232 can be approximately half the width of the cover layer, in which case they intersect with the main body portion of the cover layer. When the cover layer is wrapped around the torso of a test subject, the tab portions 232 can extend beyond each other to be attached to respective portions of the cover layer at the ends of the cover layer opposite the respective tab portions.

[0085] According to an optional aspect, the cover layer may have an inner surface that includes a biocompatible nonwoven adhesive. The nonwoven adhesive may optionally be elastic in the longitudinal dimension 201. In an embodiment, the cover layer may comprise product number 1776 medical nonwoven tape made by 3M.

[0086] A release layer 250 may be disposed over and cover the underside of the biocompatible, breathable polyurethane adhesive on the inner surface 216 of the inner layer 212 and over the underside of the hydrogel layer 224. The release layer may protect the adhesive prior to application of the treatment assembly to a test subject. The release layer 250 may have a shape that is complementary to the shape of the cover layer 230. The release layer may include a separate tab 252 configured to cover the tab portion 232 of the cover layer 230.

[0087] The treatment assembly may include at least one temperature sensor 260, such as a thermistor or thermocouple (not shown, but the temperature sensor 260 may have a location corresponding to the temperature sensors 414 and 414' of FIGS. 10B and 11B). The at least one temperature sensor may optionally be integral with the flexible circuit board 202. The at least one temperature sensor may include multiple temperature sensors. For example, a temperature sensor may be located on the flexible circuit board 202 proximate each lead end 208. The temperature sensor 260 may provide feedback to prevent overheating of the treatment assembly or causing burns to the test subject. For example, based on a temperature reading from the temperature sensor 260 exceeding a threshold value (e.g., 40° C.), the TTFields generating device 18 may adjust or stop induction of TTFields at one or more electrodes. The system 10 may also receive feedback from the temperature sensor 260 to maintain a consistent temperature in a control heater treatment assembly as further disclosed herein. Optionally, a temperature sensor may be placed in each hole in each plate to measure the temperature between the plate and the hydrogel. In a further aspect, the temperature sensor may be placed on the side of each plate opposite the hydrogel, thereby avoiding the need to form holes in the plate (and potentially weaken the plate unnecessarily). In a further embodiment, the temperature sensor may be placed on the side of each plate (e.g., within 3 millimeters of the edge of the plate), in the area of ​​the hydrogel. For example, as shown in FIG. 10A, a pair of plates 412 may share a single layer of hydrogel 410, and each temperature sensor may be placed between each pair of plates.

[0088] The portion of the treatment assembly that bears against the test subject (e.g., excluding the weight of the cable) can optionally weigh less than about 10% of the subject's body weight. For example, the portion of the treatment assembly that bears against the test subject can weigh less than about 2.5 grams for a typical mouse.

[0089] The treatment assembly may be flexible enough to conform to a portion of the torso of the test subject 12. Optionally, in a pre-use configuration as shown in Figure 8, the treatment assembly has a length in the longitudinal dimension 201 that is sufficient to extend around the girth of the test subject's torso (when placed on the animal and during use). Optionally, the treatment assembly may be pre-formed into a three-dimensional shape configured to be complementary to the shape of the torso of the test subject 12.

[0090] Optionally, the kit may include multiple treatment assemblies 200 having various lengths in the longitudinal dimension 201 (in a pre-use configuration). In this manner, the test subject may be fitted with an appropriately sized treatment assembly (depending on the animal's girth / circumference). For example, an appropriately sized treatment assembly may be comfortably wrapped around the girth of the test subject's torso. Optionally, additional cover material (which may be the same material as the outer layer, for example) may be provided to reinforce attachment to the test subject as well as to seal the edges of the adhesive material from dirt and debris that may prevent good contact.

[0091] 9, the treatment assembly 200' may be configured to treat a subcutaneous tumor. The treatment assembly 200' has a structure generally similar to that of the treatment assembly 200, with an inner layer 212' defining an opening 218' that receives the plate 210'. It is contemplated that, optionally, a hydrogel 224' may be received within the opening 218'. A flexible circuit board 202' may include a cable 204', a connector end 206' configured to couple to a swivel 300 (FIG. 1), and one or more lead ends 208' at the lead end opposite the connector end 206'. The lead ends 208' may be configured to couple with a respective plate 210'. An outer layer 230' may be attached to the upper surface of each of the inner layers and the lead ends. A release layer 250' with separate tabs 252' may be attached to the inner layer 212' and the underside of the hydrogel 224'. The outer layer 230 ′ and the release layer 250 ′ may be of a similar construction to the outer layer 230 and the release layer 250 .

[0092] The inner layer 212', the circuit board 202', and the cover layer 230' can cooperate to define a through hole 270' extending through the thickness of the treatment assembly 200' (other than the inner release layer, if present) and configured to receive a subcutaneous tumor. Optionally, the through hole 270' can have a diameter between 10 mm and 15 mm. Optionally, the through hole 270' can have a maximum diameter of about 15 mm. A cap 272' can extend over the through hole 270', the cap 272' defining a receiving portion 274' therein configured to receive an outwardly extending portion of a subcutaneous tumor. The cap 272' can be attached to the cover layer 230'. For example, the cap 272' can define a radially extending periphery 276'. An adhesive ring 278' can engage the flange 276' and the outer layer 230' to secure the cap 272' to the outer layer. The cap 272' can prevent dirt and debris (eg, sawdust floor covering) from entering the holes and can prevent contact between the treatment assembly and the test subject.

[0093] In the illustrated embodiments, the openings 218' through which the plate 210' is received can have a predetermined relationship to the through-hole 270'. Optionally, in these embodiments, the openings 218' can be circumferentially spaced about the periphery of the through-hole 270' (and thus the periphery of the subcutaneous tumor as the tumor extends through the through-hole 270'), as shown in Figures 9 and 11A.

[0094] According to certain embodiments, the kit may include multiple treatment assemblies 200' having through holes 270' of various diameters and caps 272' of corresponding various sizes. Multiple treatment assemblies 200' having through holes of various diameters may optionally have corresponding various spacings between the lead ends 208' and the plate 210'. In this manner, the test subject 12 may be fitted with a treatment assembly 200' sized appropriately for its subcutaneous tumor. Optionally, the kit may further include multiple caps (optionally of the same size and / or of different sizes) so that the caps can be replaced over the course of treatment.

[0095] The length of the cable 204, 204' may be selected based on the dimensions of the enclosure so that the test subject 12 cannot be wrapped by or entangled with the cable. A certain amount of slack may be attached to the back of the test subject to reduce the amount of free length of the cable. Thus, the cable may have a working portion that is not attached to the test subject, which may define the working length of the cable. According to an embodiment, the working length of the cable may be selected such that the cable does not have enough length to hang down from the back of the test subject and touch the floor when the test subject is directly under the swivel. Thus, the maximum working length of the cable may be approximated as the height of the cage (or the height at which the cable attaches to the swivel) plus twice the height of the test subject. In a further embodiment, the cable length may be selected such that the cable does not have enough slack to hang down from the back of the test subject to within a threshold distance t (FIG. 6) of the cage floor. Thus, the maximum working length of the cable can be approximated by the height above the floor when the cable attaches to the swivel plus twice the height of the test subject minus twice the threshold distance. Optionally, the threshold distance can be 0 millimeters, 1 millimeter, 2 millimeters, 4 millimeters, 6 millimeters, 10 millimeters, or greater. In some embodiments, the threshold distance can range from about 1 mm to about 10 mm, or from about 2 mm to about 6 mm. It is still further contemplated that due to the limited flexibility of the cable, the length of the working portion of the cable can be slightly longer than twice the height of the subject plus the height of the cable without the cable being able to reach the floor of the cage.

[0096] To construct the treatment assembly 200, each plate of the plurality of plates 210 may be placed in an opening in the inner layer of the treatment assembly. For example, in an embodiment, a pair of plates may be placed in each opening. Alternatively, a single plate may be placed in each opening. Each lead end of the plurality of lead ends may be placed in contact with a respective plate of the plurality of plates. As previously mentioned, the lead ends form respective electrodes when coupled with a plate as disclosed herein. A cover layer may be attached to an outer surface of the inner layer to cover the plurality of electrodes. A layer of hydrogel may be applied to an inferior surface of each plate of the plurality of plates. In some aspects, pairs of plates that are placed in a shared opening in the inner layer may also share a layer of hydrogel. Optionally, hydrogel may be applied over adjacent portions of the inner surface of the inner layer.

[0097] With reference to FIGS. 24-29, it is contemplated that in further embodiments, the treatment assembly 200″ may be configured to be at least partially placed on the head of a test subject. For example, the head covering portion 9a of the treatment assembly 200″ may be coupled to at least a portion of the head of a mouse, as shown in FIG. 26. The head covering portion 9a of the treatment assembly 200″ may include a head-wearable layer 6 configured to extend over a portion of the test subject's head and be coupled to the test subject via an adhesive disposed on one or more inner surfaces thereof. The treatment assembly 200″ may further include a torso covering portion 9b configured to be placed on the body (e.g., torso) of the test subject (e.g., wrapped around the body / torso of the test subject, as further disclosed herein). The torso covering portion 9b of the treatment assembly 200" may include an inner adhesive wearable layer 1 configured to engage the body (optionally, the skin) of a test subject. A flexible circuit board 5 may include a plurality of lead ends. An end 8 of the flexible circuit board may be in communication with a TTFields generating device 18 (FIG. 1). An inner adhesive patch 4 may be coupled to the skin-engaging side of the adhesive portion 6, with a portion of the flexible circuit board 5 disposed between the inner adhesive patch 4. An outer wearable layer 7 may be coupled to the outside of the torso covering portion 9b of the treatment assembly.

[0098] A plate (e.g., a ceramic plate) 3 can be coupled to the lead ends of the flexible circuit board. A hydrogel 2 can be disposed beneath the ceramic plate so as to engage the patient's skin. The inner adhesive wearable layer 1 of the torso covering portion 9b can define at least one opening (optionally multiple openings) that receives a corresponding portion of the hydrogel 2.

[0099] The flexible circuit board 5 can include a plurality of lead ends (and corresponding plurality of electrodes 602) configured to be placed on the head of a test subject, and one or more lead ends (e.g., two lead ends) (and corresponding plurality of electrodes 604) configured to be placed on the body (e.g., torso) of the test subject. In the illustrated embodiment, the plurality of lead ends (for placement on the head) are configured to underlie the head wearable layer 6, and the one or more lead ends (for placement on the torso) are configured to underlie the outer wearable layer 7 of the torso covering portion 9b, with each lead end covering a respective ceramic plate 3 and hydrogel portion 2. Optionally, the plurality of lead ends configured to be placed on the test subject's head may include a first group of lead ends (e.g., three lead ends corresponding to electrode 602a) configured to be placed on a first side of the test subject's head (relative to a median plane 606 that bisects the test subject into left and right sides) and a second group of lead ends (e.g., three lead ends corresponding to electrode 602b) configured to be placed on a second, opposite side of the test subject's head (relative to the median plane). The one or more lead ends configured to be placed on the test subject's body (e.g., torso) may comprise a first lead end (corresponding to electrode 604a) that is placed on a first side of the test subject's body relative to the median plane and a second lead end (corresponding to electrode 604b) that is placed on a second side of the test subject's body relative to the median plane. 28, it is contemplated that a first lead end disposed on a first side of the body can cooperate with a second group of lead ends on a second side of the test subject's head to provide TTFields, and a second lead end disposed on a second side of the body (torso) can cooperate with the first group of lead ends on the first side of the test subject's head to provide TTFields. The TTFields may be provided in an alternating manner to provide or facilitate crossing of TTFields.

[0100] In exemplary embodiments, the flexible circuit board 5 may include an undulating (e.g., switchback), serpentine, wavy, or zigzag portion (generally referred to as an "alternating shaped portion" 700) configured to facilitate flexibility to allow the test subject to move its neck. It is contemplated that during use, the alternating shape of this portion of the flexible circuit board 5 may provide a reduced starting length (avoiding unnecessary slack in the cable) while also allowing for increased length and straightening to accommodate the test subject's movements (e.g., neck extension, twisting, and rotation). In these embodiments, as shown in Figures 24-25 and 27-29, the alternating shaped portion may be disposed between the head covering portion 9a and the torso covering portion 9b. It is further contemplated that the alternating shaped portion of the flexible circuit board 5 may be disposed between a plurality of lead ends (for placement on the head) and at least one lead end (for placement on the torso).

[0101] Example non-limiting dimensions of the treatment assembly 200'' are provided in FIG. 29 in millimeters.

[0102] It is contemplated that the materials and properties of the inner adhesive wearable layer 1 of the torso covering portion 9b may be the same as or similar to the materials and properties of the cover layer 212, 212' disclosed herein for the treatment assembly 200, 200'. Similarly, it is contemplated that the materials and properties of the hydrogel 2 of the treatment assembly 200" may be the same as or similar to the materials and properties of the hydrogel 224, 224' disclosed herein for the treatment assembly 200, 200'. It is further contemplated that the materials and properties of the plate 3 of the treatment assembly 200" may be the same as or similar to the materials and properties of the plate 210, 210' disclosed herein for the treatment assembly 200, 200'. It is further contemplated that the materials and properties of the flexible circuit board 5 may be the same as or similar to the materials and properties of the flexible circuit board 202, 202' disclosed herein for the treatment assembly 200, 200'. Still further, it is contemplated that the materials and properties of the head wearable layer 6 and outer wearable layer 7 of the treatment assembly 200" may be the same as or similar to the materials and properties of the cover layer 230 / outer layer 230' disclosed herein for the treatment assemblies 200, 200'.

[0103] 10A-11B, the control heater treatment assembly 400 can be coupled to a control test subject and can be configured to mimic many, all, or substantially all of the aspects of the treatment assembly 200. Similarly, the control heater treatment assembly 400' can be configured to mimic all or substantially all of the aspects of the treatment assembly 200' and can have a similar structure and operation as described for the control heater treatment assembly 400. Similarly, the control heater treatment assembly can be configured to mimic all or substantially all of the aspects of the treatment assembly 200" and can have a similar structure and operation as described for the control heater treatment assembly 400. For example, the control heater treatment assembly 400 can be configured to generate heat to maintain a similar temperature relative to the skin of the control test subject, thereby minimizing differences between the characteristics of the control group and the test group. As another example, the control heater treatment assembly 400 can be configured to have substantially the same or generally the same weight as a treatment assembly capable of generating TTFields as further disclosed herein.

[0104] The control heater assembly 400 may include a flexible circuit board 402. The flexible circuit board 402 may include a cable 404 and a connector end 406 configured to couple to the swivel 300. The flexible circuit board may include a plurality of resistive heaters disposed at locations corresponding to where electrodes are positioned on the treatment assembly 200. For example, the flexible circuit board 402 may include eight zones 410 (e.g., two rows of four zones 410) where electrodes may be on a corresponding treatment assembly. More broadly, the flexible circuit board 402 may have any desired number of zones, each corresponding to the location of an electrode on a corresponding treatment assembly. Optionally, each zone 410 may include two resistive heaters 412 (shown generally in FIG. 10A as a single unit separate from the circuit board 402 and in FIG. 11 in detail as components of the circuit board 402). A temperature sensor 414 may be disposed in each zone 410, optionally in the center of each zone 410, equally spaced between the heaters 412. The heaters 412 may optionally comprise glass plates.

[0105] Optionally, the control heater assembly 400 may include an inner layer 420 that defines a plurality of through holes through which the heater 412 may be placed. Optionally, the control heater assembly 400 may include a cover layer 430 that extends over an upper side of the flexible circuit board. A release liner 440 may be releasably attached to a lower surface of the inner layer. The inner layer 420 and the cover layer 430 may include the same material and shape as the corresponding treatment assembly to feel similar to the test subject. Optionally, a layer of hydrogel 416 may cover the lower side of the flexible circuit board 402. Similarly, the control heater assembly 400' may have a structure corresponding to that of the treatment assembly 200', having a flexible circuit board 402', an inner layer 420', a release liner 440', a cover liner 430', a cap 450', and an adhesive ring 460'. Similarly, control heater assemblies that mimic the shape, weight, heat, and other perceived experiences of the treatment assembly 200'' are also contemplated.

[0106] The control heater assembly 400 can be coupled to the TTFields generation device 18 via the swivel 300. The swivel 300 can control the output of the resistive heater 412 based on feedback from the temperature sensor 260. In an embodiment, the control heater assembly 400 can maintain a set temperature (e.g., 38.5° C. or 39° C.) to mimic the temperature that a corresponding treatment assembly 200, 200', 200" reaches as a side effect of providing TTFields. In a further embodiment, the control heater assembly 400 can be selectively controlled to maintain a temperature that matches the temperature of a treatment assembly in a corresponding test subject receiving TTFields treatment.

[0107] The control heater assembly 400, 400' may further have a weight that is similar to the weight of the respective treatment assemblies 200, 200', 200". Thus, the control heater assembly may produce a similarly perceived experience in the test subject. In this manner, the effect of TTFields on tumor growth may be separated from other aspects of the test procedure.

[0108] In exemplary embodiments, kits may be provided having both a control heater assembly 400, 400′ and a treatment assembly 200, 200′, 200″. In these embodiments, it is contemplated that each treatment assembly in the kit may have a corresponding / mate control heater assembly located in the same kit, thereby maximizing uniformity between the control and experimental / treatment groups.

[0109] It is contemplated that the embodiments disclosed herein, in addition to providing TTFields, can be used to provide other electrical currents, electric fields, and heat to different body parts of a test subject.

[0110] In some optional embodiments, a thick treatment assembly (and corresponding control heater assembly) for a test subject with a thick torso may have a length (relative to the longitudinal axis 201) of about 200 mm to about 250 mm, a width of about 100 mm to about 130 mm (optionally about 110 mm to about 115 mm), and a thickness of about 1.6 mm to about 1.7 mm. In some optional embodiments, a thin treatment assembly (and corresponding control heater assembly) for a test subject with a thin torso may have a length of about 200 mm to about 250 mm, a width of about 80 mm to about 115 mm (optionally about 100 mm to about 110 mm), and a thickness of about 1.6 mm to about 1.7 mm. In a further optional embodiment, the treatment assembly for subcutaneous tumors (and corresponding control heater assembly) may have a length of about 290 mm to about 330 mm, a width of about 65 mm to about 95 mm, and a thickness of about 1.6 mm to about 1.7 mm.

[0111] ring body It is contemplated that a test subject may have a tendency to bite or bite off the treatment assembly 200, 200', 200" or the control heater treatment assembly 400, 400'. With reference to FIGS. 30-32, it is contemplated that to discourage such behavior, the annulus 500 may be ring-shaped. Optionally, the annulus 500 may have two opposing ends that join together to form a ring shape. For example, the annulus 500 may be disposed at a first end 506 and receive into one or more holes 504 at an opposing second end 508. The protrusion 502 may include a protrusion 502 configured to be inserted into the hole. The protrusion 502 may have an enlarged distal end having a diameter greater than the diameter of the one or more holes 504 such that when inserted into the hole, the protrusion 502 cannot be inadvertently removed (due to the enlargement between a surface of the protrusion and a portion of the second end that defines the hole). To accommodate different sized test subjects, it is contemplated that the one or more holes 504 may include a plurality of holes 504 spaced about the circumference of the annulus 500 such that the annulus may have selectable operating diameters depending on the hole into which the protrusion 502 is inserted.

[0112] Optionally, the annulus 500 may have an inner surface 510 that is jagged, serrated, or toothed. Optionally, the annulus 500 may have an outer surface 512 that is axially tapered. The annulus 500 may be oriented such that the outer surface tapers in a direction away from the test subject's head.

[0113] It is contemplated that both the excess weight of the annulus and sound reflections may shorten the life of the test subject. Thus, in certain embodiments, the annulus 500 may optionally define a plurality of holes 514 that may extend axially throughout (through the thickness of the annulus). The holes 514 may reduce the amount of material, and therefore the weight of the annulus, and may minimize sound reflections that may cause stress to the test subject.

[0114] The annulus 500 may optionally be flexible. Optionally, the annulus may comprise a polymer, such as, for example, silicone.

[0115] Swivel Assembly 12 and 15, the swivel 300 may be mounted to the cover 120 within a swivel housing 180. The swivel housing 180 may include a sidewall 182 that is integral with the cover 120. The swivel housing 180 may receive a removable internal circumferential insert 184. The swivel housing may further include a top cover 186 that couples to the sidewall 182.

[0116] The pivot 300 may include a damping plate 302 that attaches to the top cover 186 via screws or other fasteners. The top cover 186 may be part of the pivot module. The damping plate 302 may be coupled to a motor mounting plate 304 via screws 306. The pivot 300 may have a central axis 308 about which a motor 310 may rotate. The motor 310 may be coupled to the motor mounting plate 304 via screws 312. A rotatable base 314 may be attached to the motor 310 via screws 316. Thus, the rotatable base may be rotatable relative to the motor mounting plate 304 via the motor. A bearing housing 316 may be coupled to the rotatable base 314 via standoffs 318. The rotatable base 314 may define depending tabs 320 that may be coupled to a flexible circuit assembly 322.

[0117] In an optional embodiment, the top cover 186 may include at least one input device (e.g., a button) configured to start and stop a treatment (e.g., TTFields or heat). Optionally, the at least one input device may include multiple input devices, each configured to control the operation of a different component of the system. In an embodiment, each input device may be configured to control the application of TTFields and the application of heat. In further embodiments, the input device may be configured to start and stop the operation of the swiveller. In further embodiments, the top cover 186 may include a display configured to show information such as, for example, an experiment identification (e.g., cage number, electrode type), or an operating mode (e.g., standby, treatment, heat, pause). In various embodiments, the top cover 186 may provide a communication port that may be in communication with the swiveller 300 to provide communication between the signal generator 12 (FIG. 1) and the treatment / control heater assembly.

[0118] 13 and 15, the flexible circuit assembly 322 may include a printed circuit board (PCB) 324 having an input / output connector 326 attached thereto. The connector 326 may provide communication to the upper portion of the pivot. The printed circuit board 324 may define a patterned portion 328 extending between a base portion 330 and a cable connector end 332. The patterned portion 328 may have a structure that may cause the printed circuit board 324 to twist such that the connector end 332 may pivot relative to the base portion 330, as described further herein. In an exemplary embodiment, the patterned portion 328 may have a serpentine, wavy, zigzag, or undulating pattern. A pair of sensor connector portions 334 may extend from the base portion 330.

[0119] 18A, 18B, and 19, the bearing housing 316 may contain a bearing 340 (e.g., a ball bearing or a nylon bearing) that may receive and support a pivot body 342 within an internal race. The pivot body 342 may define a slot 344 that may receive a connector end 332 of the printed circuit board 324. The slot 344 may receive and engage the connector end 332 such that the connector end pivots about the central axis 308 and the pivot body may correspondingly pivot. (The figures show the connector end 332 remaining in place as the pivot body pivots, but it should be understood that the connector end may pivot with the pivot body during use.) The pivot body 342 may define a cantilevered tab 346 that extends parallel to the central axis 308.

[0120] A centering spring 348 may extend from a standoff 350 mounted to the bearing housing 316 for engaging a protrusion 352 or other radially extending surface that is spaced or extends away from the central axis 308 of the pivot 300. The centering spring 348 may bias the pivot 316 toward a neutral position 354. In use, the pivot may be in the neutral position 354 when there is no or substantially no torque applied to the printed circuit board 324.

[0121] 15, 18A, 18B, and 19, a pair of sensors 356 (e.g., electro-optical sensors such as VISHAY TCPT1600X01 sensors) can be attached to the bearing housing 316 via respective sensor mounts 358. The sensors 356 can communicate with the PCB 324 at the sensor connector portion 334. The sensors 356 can communicate with a processor (e.g., a PLC controller in a circuit board 359 as shown in FIG. 23). The sensors can have a light source, a photodetector, and an optical path between the light source and the photodetector. The sensors 356 can be positioned such that the cantilevered tabs 346 obstruct both sensors 356 when the pivot 316 is in a neutral position. When the test subject walks in the cage, he can twist the cable 204 (FIG. 8), thereby applying a twist to the pivot 342 and pivoting it from its neutral position. When the pivot body pivots sufficiently in a first direction 360 (see FIG. 19 ) from the neutral position 354, the cantilevered tab 346 is out of the optical path of the first sensor 356A, which can detect light from the light source at the photodetector. In this manner, the pivot 300 can detect a twist in the cable in the first direction. The processing device can rotate the motor 310 in the first direction 360 to release the twist in the cable. Optionally, the pivot can be configured to remain stationary until a minimum threshold angle is reached from the neutral position 354 to prevent excessive movement that may cause wear on the motor. Optionally, the motor can rotate a minimum angular distance to minimize an excessive number of small movements. Similarly, when the pivot body is sufficiently pivoted in a second direction 362 (opposite the first direction) from the neutral position 354, the second optical sensor 356B can detect such a condition and the processor can cause the motor to rotate in the second direction to release the twist in the cable. In this manner, the pivot can limit the amount of twist in the cable 204, thereby allowing free movement of the test subject within the cage.

[0122] A limiting portion 364 may be attached to each sensor mounting portion 358. Each limiting portion 364 may include a centrally extending portion that may act as a stop to prevent the pivot body from pivoting beyond a threshold angle from the neutral position 354, thereby preventing the printed circuit board 324 from being destroyed.

[0123] The pivot 342 may define a connector 380 configured to receive the connector end 206, 206', 406, 406' of the flexible circuit board and electrically couple the flexible circuit board to the PCB 332. For example, the connector 380 may comprise a USB-C connector that is complementary to the connector end of the flexible circuit board (e.g., a female USB-C connector). Optionally, the connector 380 may comprise a CAN bus connection.

[0124] The pivot may include slip rings that can maintain electrical communication through the pivot to allow communication between the treatment assembly 200 (or treatment assembly 200' or treatment assembly 200"), the heater assembly 400 (or heater assembly 400'), and the TTFields generation device 18. The slip rings can allow communication of at least 20 communication channels.

[0125] The computing device 1001 can communicate with the swivel unit 300 (e.g., through cable 20 or other cables) to track and / or record various metrics. In further embodiments, the computing device 1001 can be embodied as a controller on the PCB 359 (FIG. 23). For example, the metrics can include some or all of the following metrics: number of rotations, number of rotations in a first selected time period, frequency of motor motion, frequency of motor motion in a second selected time period, number of motor motions with changes in direction, number of motor motions in a third selected time period with changes in direction, duration of constant motion, and a log of motor motions and corresponding times of motor motions. Such metrics can indicate abnormal behavior in the test subject. Additionally, such metrics can indicate a malfunction of the swivel unit 300. In an embodiment, a warning (e.g., a warning light or an audible warning) can be activated to notify a user that the swivel unit 300 is malfunctioning or that the test subject is behaving abnormally. In further embodiments, a computing device or controller in communication with the swivel section may be configured to receive user input. The user input may define one or more thresholds, such as, for example, a frequency threshold (e.g., frequency of change in direction of rotation) or a time threshold (e.g., duration of a certain rotation threshold). When each threshold is exceeded, an alarm may be activated.

[0126] In further embodiments, the computing device can generate and output a log report comprising at least one of the collected metrics. The log report can further output a comparison of the metrics based on a comparison with an average metric. The average metric can be an average metric for similar test subjects, or an average metric for a given subject over a selected time period (e.g., over the course of hours, days, or weeks). For example, the average metric can be the average amount of movement that the test subject moves each day. Thus, it is contemplated that a decrease in the amount of movement each day may indicate a deterioration in the health of the test subject. It is further contemplated that excessively high or low amounts of movement compared to other similar test subjects can indicate the relative health of the test subject. It is further contemplated that the monitoring of various metrics can enable identification of changes to ensure that the animal test subjects survive beyond the end of the experimental period.

[0127] Referring to FIG. 1, a plurality of test subjects 12 of an experimental group 14 may be fitted with respective treatment assemblies. The treatment assemblies may be selected to treat a specific tumor (e.g., treatment assembly 200 for organ tumors, or treatment assembly 200' for subcutaneous tumors). The treatment assemblies may be appropriately sized. For example, for organ tumors, the longitudinal length of the treatment assembly may be appropriate for wrapping comfortably around the girth of the test subject's torso along the torso in a given tumor. For subcutaneous tumors, the treatment assembly's through-hole and cap may be selected to fit the subcutaneous tumor with minimal excess space. The length of the treatment assembly's cable may be selected to allow the test subject to freely navigate the floor area of ​​the enclosure, while not providing excess length that may become entangled, as disclosed herein. The release liner may be removed to allow the adhesive to engage the skin of the test subject. The test subject's hair may be removed in the application area by a clipping device and / or a hair removal cream (e.g., VEET hair removal cream). Similarly, test subjects 12 in the control group may be fitted with a respective control heater treatment assembly 400 or control heater treatment assembly 400' (to match their experimental group counterparts).

[0128] The treatment assembly may be placed on the body such that the electrodes are placed as close as possible to the tumor. In various embodiments, the treatment assembly (or control heater assembly) may be placed on the body of the test subject to minimize or eliminate interference with natural movement. For example, the treatment assembly may be placed away from the hind or front limbs of the mouse to allow natural movement. The treatment assembly may be selected at least in part based on the size of the mouse. For example, a thin treatment assembly may be placed on a mouse that weighs less than 23 grams, and a thick treatment assembly may be placed on a mouse that weighs more than 23 grams.

[0129] The treatment arrangement (or control heater assembly) can be oriented such that the cable extends toward the hips / buttocks of the test subject. It is contemplated that the subcutaneous treatment assembly and the control heater assembly can have a bend (e.g., a 90 degree bend) that allows the cable to extend to the middle of the test subject's back and then along the back toward the hips. The bend can be provided in either direction depending on the side of the test subject on which the subcutaneous tumor is placed. An adhesive (e.g., a bandage) can be placed on the test subject to enhance adhesion of the treatment assembly (or control heater assembly).

[0130] A test subject can be placed within each enclosure of the cage assembly. The connector ends of each treatment assembly and control heater treatment assembly 400 can be attached to the respective swivels.

[0131] The treatment assembly may be controlled to provide TTFields to the test subject. For example, with reference to FIGS. 20 and 21, TTFields of 50 kHz to 500 kHz (optionally 150 kHz to 500 kHz) may be delivered to an organ tumor 22 (FIG. 20) or a subcutaneous tumor 22' (FIG. 21). Optionally, the TTFields may be delivered sequentially in another axis of propagation (to provide an alternating electric field). For example, a first pair of opposing electrodes may apply a first electric field across the tumor along a first axis of propagation 60. A second pair of electrodes positioned to have a second axis of propagation 62 that is perpendicular or substantially perpendicular to the first axis of propagation may alternate with the first pair of opposing electrodes to provide an alternating electric field across the tumor. For treatment assembly 200, each electrode may cooperate with a respective electrode positioned furthest from its location (e.g., on the other side of the test subject's body) to provide alternating TTFields. Optionally, each electrode may be independently controlled to provide a tailored treatment. The control heater treatment assembly may be controlled via the TTFields generating device or other control device to provide placebo heat to match or substantially match the temperature of the treatment assembly. Treatment may optionally last for about 1-2 weeks.

[0132] The tumors of the experimental group and the tumors of the control group can be compared during and after treatment. For example, for subcutaneous tumors, the cap can be removed to expose the subject while the treatment assembly is still attached to the subject, and the size of the tumor can be measured with a caliper. Organ tumors can be measured, for example, via magnetic resonance imaging (MRI), ultrasound examination (US), or computed tomography (CT) scans. The treatment assembly can be removed prior to such scans.

[0133] Computer Devices FIG. 22 illustrates a system 1000 including an exemplary configuration of a computing device 1001 for use in the system 10.

[0134] The computing device 1001 may include one or more processing units 1003, a system storage 1012, and a bus 1013 that couples various components of the computing device 1001, including the one or more processing units 1003, to the system storage 1012. With multiple processing units 1003, the computing device 1001 may utilize parallel computing.

[0135] Bus 1013 may comprise one or more of several possible types of bus structures, such as a memory bus, a memory controller, a peripheral bus, an accelerated graphics port, and a processor or local bus using any of a variety of bus architectures.

[0136] The computing device 1001 can operate on and / or comprise a variety of computer readable media (e.g., non-transitory). The computer readable media can be any available media that is accessible by the computing device 1001 and includes non-transitory, volatile, and / or non-volatile media, removable and non-removable media. The system storage 1012 has computer readable media in the form of volatile memory, such as random access memory (RAM), and / or non-volatile memory, such as read only memory (ROM). The system storage 1012 can store data, such as temperature data 1007 (i.e., data from signals received by the electrodes), and / or program modules, such as an operating system 1005 and a TTFields delivery software 1006, that are accessible by and / or operated by the one or more processing units 1003.

[0137] The computing device 1001 may also include other removable / non-removable, volatile / non-volatile computer storage media. The mass storage device 1004 can provide non-volatile storage of computer code, computer readable instructions, data structures, program modules, and other data for the computing device 1001. The mass storage device 1004 can be a hard disk, a removable magnetic disk, a removable optical disk, a magnetic cassette or other magnetic storage device, a flash memory card, a CD-ROM, a digital versatile disk (DVD) or other optical storage, a random access memory (RAM), a read only memory (ROM), an electrically erasable programmable read only memory (EEPROM), or the like.

[0138] Any number of program modules may be stored on the mass storage device 1004. The operating system 1005 and the TTField delivery software 1006 may be stored on the mass storage device 1004. One or more of the operating system 1005 and the TTField delivery software 1006 (or some combination thereof) may comprise the program modules and the TTField delivery software 1006. Temperature data 1007 may also be stored on the mass storage device 1004. The temperature data 1007 may be stored in any of one or more databases known in the art. The databases may be centralized or distributed across multiple locations within the network 1015.

[0139] A user can enter commands and information into the computing device 1001 using input devices (not shown). Such input devices include, but are not limited to, keyboards, pointing devices (e.g., computer mice, remote controls), microphones, joysticks, scanners, tactile input devices such as gloves and other body coverings, motion sensors, etc. These and other input devices may be connected to the one or more processing units 1003 using a human-machine interface 1002 coupled to a bus 1013, but may also be connected by other interface and bus structures, such as a parallel port, a game port, an IEEE 1394 port (also known as a Firewire port), a serial port, a network adapter 1008, and / or a universal serial bus (USB).

[0140] A display device 1011 may be connected to the bus 1013 using an interface such as a display adapter 1009. It is contemplated that the computing device 1001 may have more than one display adapter 1009 and that the computing device 1001 may have more than one display device 1011. The display device 1011 may be a monitor, an LCD (liquid crystal display), a light emitting diode (LED) display, a television, a smart lens, smart glass, and / or a projector. In addition to the display device 1011, other output peripheral devices may include components such as speakers (not shown) and a printing device (not shown) that may be connected to the computing device 1001 using the input / output interface 1010. Any step and / or result of the method may be output (or caused to be output) in any form to an output device. Such output may be any form of visual representation, including, but not limited to, text, graphics, animation, audio, tactile, etc. The display unit 1011 and the computing device 1001 may be part of one device or may be separate devices.

[0141] The computing device 1001 can operate in a networked environment using logical connections to one or more remote computing devices 1014a, 1014b, 1014c. The remote computing devices 1014a, 1014b, 1014c can be personal computers, computing stations (such as workstations), portable computers (e.g., laptops, mobile phones, tablet devices), smart devices (e.g., smartphones, smart watches, activity trackers, smart apparel, smart accessories), security and / or surveillance devices, servers, routers, network computers, peer devices, edge devices, or other general network nodes. The logical connections between the computing device 1001 and the remote computing devices 1014a, 1014b, 1014c can be made using a network 1015, such as a local area network (LAN) and / or a general wide area network (WAN). Such network connections can be through a network adapter 1008. The network adapter 1008 can be implemented in both wired and wireless environments. Such networking environments are conventional and commonplace in homes, offices, enterprise-wide computer networks, intranets, and the Internet. It is contemplated that remote computing devices 1014a, 1014b, 1014c may optionally include some or all of the components disclosed as being part of computing device 1001.

[0142] Although application programs and other executable program components, such as the operating system 1005, are illustrated herein as separate blocks, it is recognized that such programs and components may reside at various times in different storage components of the computing device 1001 and be executed by one or more processors 1003 of the computing device 1001. An implementation of the electrode data processing software 1006 may be stored on or transmitted across some form of computer readable media. Any of the disclosed methods may also be performed by processor executable instructions embodied in a computer readable medium.

[0143] Example Embodiments In view of the described products, systems, methods, and variations thereof, certain more specifically illustrated aspects of the present invention are described herein below. However, these specifically proposed aspects should not be construed as having a limiting effect on any different claims that include different or more general teachings described herein, or as limiting the "specific" aspects in any way other than to the inherent meaning of the literal term as used herein.

[0144] Aspect 1A: A cage assembly comprising at least one enclosure, each having a floor defining a floor area having a major dimension, a cover having a bottom surface, a spacing between the bottom surface of the cover and the floor defining a cage height, and at least one sidewall extending between the floor and the cover, wherein a ratio of the cage height to the major dimension of the floor area of ​​each of the at least one enclosure is at least 0.70.

[0145] Embodiment 2A: The cage assembly of embodiment 1A, wherein the at least one enclosure comprises a first enclosure and a second enclosure.

[0146] Embodiment 3A: The cage assembly of embodiment 1A, wherein the at least one enclosure comprises a first enclosure and a second enclosure.

[0147] Embodiment 4A: The cage assembly of embodiment 2A or embodiment 3A, wherein the first enclosure and the second enclosure share a common side wall separating a floor region of the first enclosure from a floor region of the second enclosure.

[0148] Embodiment 5A: The cage assembly of embodiment 4A, wherein the common side wall defines at least one opening between the first enclosure and the second enclosure.

[0149] Aspect 6A: The cage assembly of Aspect 5A, wherein the first enclosure and the second enclosure each include a respective shelter subassembly extending inwardly from a common side wall within the enclosure, the shelter subassembly at least partially surrounding an opening in the common side wall.

[0150] Embodiment 7A: The cage assembly of any one of Embodiments 1A to 6A, wherein each enclosure floor defines a corner, and each corner of the enclosure floor has a radius of at least 17 mm.

[0151] Embodiment 8A: The cage assembly of any one of Embodiments 1A to 7A, wherein a major dimension of the floor area of ​​each enclosure is 250 mm or less.

[0152] Embodiment 9A: The cage assembly of any one of Embodiments 2A to 8A, wherein the floor of the first enclosure and the floor of the second enclosure are integrally constructed.

[0153] Embodiment 10A: The cage assembly of any one of Embodiments 2A to 9A, wherein the cover of the first enclosure and the cover of the second enclosure are integrally constructed as a cover assembly.

[0154] Embodiment 11A: The cage assembly of embodiment 10A, wherein the cover assembly has a first opening and a second opening providing communication with the first enclosure and the second enclosure, respectively, the first opening configured to provide communication for a first cable and the second opening configured to provide communication for a second cable.

[0155] Embodiment 12A: The cage assembly of embodiment 11A, wherein the cover assembly includes a first swivel assembly and a second swivel assembly disposed in covering relationship with the first opening and the second opening, respectively, the first swivel assembly configured to receive a proximal portion of the first cable, and the second swivel assembly configured to receive a proximal portion of the second cable.

[0156] Embodiment 13A: The cage assembly of embodiment 12A, wherein the first pivot assembly and the second pivot assembly each include a motor housing and a motor received within the motor housing, the motor of the first pivot assembly configured to be coupled to a first cable to allow adjustment of the first cable, and the motor of the second pivot assembly configured to be coupled to a second cable to allow adjustment of the second cable.

[0157] Aspect 14A: The cage assembly of Aspect 1A, wherein the at least one enclosure comprises a first enclosure, the cover comprises a pivot assembly disposed in covering relationship to the first enclosure, the cover further comprising an opening providing communication with the first enclosure, the opening configured to provide communication between a cable and the pivot assembly.

[0158] Embodiment 15A: The cage assembly of embodiment 14A, wherein the pivot assembly includes a motor, the motor configured to be coupled to a proximal portion of the cable to allow adjustment of movement of the cable.

[0159] Embodiment 16A: A cage assembly of any one of embodiments 4A to 13A, wherein at least one side wall of each of the first enclosure and the second enclosure further comprises a front side wall, a rear side wall, and a lateral side wall opposite the common side wall and extending between the front side wall and the rear side wall.

[0160] Embodiment 17A: The cage assembly of embodiment 16A, wherein at least a portion of the front wall of the first enclosure and at least a portion of the front wall of the second enclosure are integrally constructed.

[0161] Embodiment 18A: The cage assembly of embodiment 16A or embodiment 17A, wherein the rear sidewall of the first enclosure and the rear sidewall of the second enclosure are integrally constructed.

[0162] Embodiment 19A: The cage assembly of embodiment 17A, wherein the front wall of the first enclosure and the front wall of the second enclosure comprise a base portion fixed to the lateral side wall of the first enclosure and the lateral side wall of the second enclosure, and a door pivotally connected to the base portion, the door configured for movement between a closed position in which the door cooperates with the front wall, lateral side wall, rear wall, and cover of the first enclosure and the second enclosure to enclose an interior space within the cage assembly, and an open position in which the interior space of the cage assembly is accessible.

[0163] Embodiment 20A: The cage assembly of embodiment 19A, wherein the door is pivotally connected to the base by a hinge connection.

[0164] Embodiment 21A: The cage assembly of embodiment 19A or embodiment 20A, further comprising a latch portion mechanically coupled to the door, the latch portion being movable between and about a latched position that prevents pivotal movement of the door when the door is in a closed position, and an unlatched position that allows pivotal movement of the door relative to the base portion.

[0165] Embodiment 22A: The cage assembly of any one of Embodiments 1A to 21A, wherein the floor, cover, and at least one sidewall of each enclosure comprises polycarbonate.

[0166] Embodiment 23A: The cage assembly of any one of Embodiments 1A to 22A, wherein at least a portion of the cover and at least one sidewall of each enclosure is transparent.

[0167] Embodiment 24A: The cage assembly of any one of Embodiments 1A to 23A, wherein the cover defines an opening configured to receive an electrical cord.

[0168] Embodiment 25A: The cage assembly of any one of Embodiments 1A to 24A, wherein the floor of each enclosure comprises padding.

[0169] Embodiment 26A: The cage assembly of any one of Embodiments 1A to 25A, wherein at least one side wall of each enclosure includes a ventilation opening.

[0170] Embodiment 27A: The cage assembly of embodiment 26A, further comprising at least one filter configured to cover at least one vent opening in at least one side wall.

[0171] Embodiment 28A: The cage assembly of embodiment 27A, further comprising a frame configured to mechanically couple the filter to at least one sidewall.

[0172] Embodiment 29A: The cage assembly of embodiment 27A, wherein the cage assembly is sealed such that all or substantially all vent air to each enclosure passes through at least one filter before entering the vent opening.

[0173] Embodiment 30A: The cage assembly of any one of Embodiments 1A to 29A, wherein the side walls of each enclosure have equal lengths.

[0174] Embodiment 31A: The cage assembly of any one of Embodiments 1A to 30A, wherein the ratio of cage height to the major dimension of the floor area of ​​each of the at least one enclosure is at least 1.0.

[0175] Embodiment 32A: A cage assembly comprising at least one enclosure, each enclosure having a floor defining a floor area having a major dimension, a cover having a bottom surface, a spacing between the bottom surface of the cover and the floor defining a cage height, and at least one sidewall extending between the floor and the cover, wherein the height h is a function of the major dimension Y of the floor according to the formula: h≧(Y2-6400) / 320, where h and Y are in millimeters.

[0176] Aspect 33A: A method comprising the steps of placing an animal subject within each enclosure of a cage assembly of any one of the previous aspects, and connecting a distal end of a cable to the animal subject within each enclosure, wherein at least 90% of the floor area of ​​the enclosure is accessible by the animal subject.

[0177] Embodiment 34A: The method of embodiment 33A, further comprising the step of connecting a proximal end of each cable to a pivot assembly, each cable having an operating portion having an operating length, each operating length being selected such that each test subject cannot be in a position within the respective enclosure where the spacing between the operating portions of the cables is within a threshold distance of the floor.

[0178] Embodiment 35A: The method of embodiment 33A or embodiment 34A, wherein the animal subject is a mouse.

[0179] Embodiment 36A: The method of embodiment 35A, wherein the cage assembly comprises a first enclosure and a second enclosure, the first mouse being placed in the first enclosure and the second mouse being placed in the second enclosure.

[0180] Embodiment 37A: The method of embodiment 36A, wherein the first enclosure and the second enclosure share a common side wall separating a floor area of ​​the first enclosure from a floor area of ​​the second enclosure, the common side wall defining at least one opening between the first enclosure and the second enclosure, the at least one opening allowing communication between the first mouse and the second mouse.

[0181] Embodiment 38A: The method of any one of embodiments 33A to 37A, wherein the electrical cord is coupled to the animal subject through a treatment assembly comprising a transducer array.

[0182] Embodiment 39A: The method of embodiment 38A, further comprising using the electrical cord and treatment assembly to apply an electric field to the animal subject within the at least one enclosure.

[0183] Embodiment 40A: The method of embodiment 39A, wherein the animal subject has a tumor and the electric field is a tumor-treating electric field.

[0184] Embodiment 41A: The method of any one of embodiments 33A to 40A, further comprising the step of inspecting or accessing the animal subject through the cage assembly without removing the animal subject from the cage assembly.

[0185] Embodiment 42A: The method of any one of embodiments 33A to 41A, further comprising the steps of removing the animal subject from the cage assembly and autoclaving the floor, cover, and at least one sidewall of each enclosure.

[0186] Aspect 1B: A treatment assembly comprising: an inner layer having an inner surface and an outer surface defining a plurality of openings extending therethrough; a plurality of plates each at least partially received within a respective one of the plurality of openings of the inner layer; a treatment circuit comprising: a cable having a plurality of electrical leads and a plurality of electrical lead ends, each electrical lead electrically connected to a respective one of the plurality of said electrical lead ends; and a cover layer attached to an outer surface of the inner layer and covering the plurality of electrical lead ends of the cable, wherein the plurality of lead ends are in contact with a respective one of the plurality of plates to define a plurality of electrodes, each electrode of the plurality of electrodes comprising a respective lead end and a respective plate.

[0187] Embodiment 2B: The treatment assembly of embodiment 1B, wherein at least one plate of the plurality of plates comprises a ceramic plate.

[0188] Embodiment 3B: The treatment assembly of embodiment 1B, wherein at least one plate of the plurality of plates comprises a glass plate.

[0189] Aspect 4B: The treatment assembly of any one of Aspects 1B to 3B, wherein at least one electrode of the plurality of electrodes is configured to generate an electric field through a corresponding plate of the plurality of plates.

[0190] Embodiment 5B: The treatment assembly of any one of embodiments 1B to 4B, wherein the multiple electrodes of the treatment circuit have respective upper surfaces and the cover layer extends over the upper surfaces of the electrodes of the cable.

[0191] Embodiment 6B: The treatment assembly of any one of embodiments 1B to 5B, wherein each plate of the plurality of plates has a lower surface and an opposing upper surface, and the treatment assembly further comprises a layer of hydrogel on the lower surface of each plate of the plurality of plates.

[0192] Embodiment 7B: The treatment assembly of any one of embodiments 1B to 6B, wherein the treatment circuit further comprises at least one temperature sensor.

[0193] Aspect 8B: The treatment assembly of any one of Aspects 1B to 7B, wherein the inner layer and the cover layer cooperate to define a hole through the treatment assembly, the hole being configured to receive a subcutaneous tumor therethrough.

[0194] Embodiment 9B: The treatment assembly of embodiment 8B, further comprising a cap extending across the hole and defining a receiving portion therein configured to receive a subcutaneous tumor, the cap attached to the cover layer.

[0195] Embodiment 10B: The treatment assembly of embodiment 8B or embodiment 9B, wherein the plurality of plates are positioned radially outward of a hole defined through the treatment assembly.

[0196] Embodiment 11B: The treatment assembly of embodiment 9B or embodiment 10B, wherein the cap comprises a rim, and the treatment assembly further comprises an adhesive ring covering the rim and securing the cap to the cover layer.

[0197] Embodiment 12B: The treatment assembly of any one of embodiments 1B to 11B, wherein the treatment assembly has a longitudinal dimension in a pre-use configuration, the cover layer comprises a biocompatible nonwoven adhesive, and the nonwoven adhesive is elastic in the longitudinal dimension.

[0198] Embodiment 13B: The treatment assembly of embodiment 12B, wherein in the use configuration, the cable extends perpendicular or substantially perpendicular to the longitudinal dimension.

[0199] Embodiment 14B: The treatment assembly of any one of embodiments 1B to 13B, wherein the inner layer comprises a biocompatible, breathable polyurethane adhesive on an inner surface of the inner layer.

[0200] Embodiment 15B: The treatment assembly of embodiment 14B, wherein the cover layer has an inner surface comprising a biocompatible nonwoven adhesive.

[0201] Embodiment 16B: The treatment assembly of any one of embodiments 1B to 15B, wherein the plurality of electrodes comprises a plurality of electric field generating electrodes, the plurality of electric field generating electrodes configured to transmit an electric field through corresponding plates of the plurality of plates.

[0202] Embodiment 17B: The treatment assembly of embodiment 16B, wherein the treatment circuit further comprises a plurality of thermistors.

[0203] Embodiment 18B: The treatment assembly of embodiment 17B, wherein a respective electrode of the plurality of electrodes and a respective thermistor of the plurality of thermistors are in communication with each plate of the plurality of plates.

[0204] Embodiment 19B: The treatment assembly of any one of embodiments 1B to 18B, wherein the treatment assembly weighs less than 2.5 grams.

[0205] Embodiment 20B: The treatment assembly of any one of embodiments 1B to 19B, wherein the treatment assembly is flexible enough to circumferentially conform to a portion of the torso of the animal subject.

[0206] Aspect 21B: The treatment assembly of any one of Aspects 1B to 20B, wherein the cable comprises an end connector disposed at an end of the cable opposite the plurality of electrodes, the end connector being configured to allow connection of the cable to an electrical signal generating device.

[0207] Embodiment 22B: The treatment assembly of embodiment 14B, further comprising a release layer in contact with the biocompatible, breathable polyurethane adhesive on the inner surface of the inner layer.

[0208] Embodiment 23B: The treatment assembly of embodiment 22B, wherein the release layer has a shape that is complementary to the shape of the cover layer.

[0209] Embodiment 24B: The treatment assembly of any one of Embodiments 1B to 23B, wherein the cover layer defines at least one tab portion extending beyond the inner layer.

[0210] Embodiment 25B: The treatment assembly of embodiment 2B, wherein the at least one tab portion comprises two opposing tab portions that are complementary to one another when the cover layer defines a circumferential hoop.

[0211] Embodiment 26B: The treatment assembly of any one of Embodiments 1B to 7B or Embodiments 12B to 25B, wherein the plurality of openings comprises a plurality of longitudinally spaced openings.

[0212] Embodiment 27B: The treatment assembly of any one of embodiments 1B to 26B, wherein the treatment circuit and the cable are integrally constructed as a flexible printed circuit board.

[0213] Aspect 28B: A method of making a treatment assembly of any one of aspects 1B to 27B, comprising the steps of placing a plurality of plates in respective openings on an inner layer of the treatment assembly, placing each of a plurality of electrodes of the treatment circuit in contact with a plate of the plurality of plates, and attaching a cover layer to an outer surface of the inner layer, the cover layer covering the plurality of electrodes of the treatment circuit.

[0214] Embodiment 29B: The method of embodiment 28B, further comprising applying a layer of hydrogel to the lower surface of each plate of the plurality of plates.

[0215] Embodiment 30B: The method of embodiment 29B, wherein the lower surfaces of at least two plates of the plurality of plates share a layer of hydrogel.

[0216] Aspect 31B: A method comprising the steps of electrically connecting at least a portion of the electrodes of a treatment assembly of any one of aspects 1B to 27B to an electrical signal generating device, attaching the treatment assembly to an animal subject having a tumor, wherein the plates of the treatment assembly surround at least a portion of the tumor, using the electrical signal generating device to generate an electrical signal, and using at least the portion of the electrodes of the treatment assembly to generate an electric field from the electrical signal through a corresponding plate of the plurality of plates.

[0217] Embodiment 32B: The method of embodiment 31B, wherein the tumor is an organ tumor, and in a pre-use configuration, the multiple openings and the multiple plates are spaced longitudinally along a longitudinal axis of the treatment assembly, and in a use configuration, the multiple openings and the multiple plates are spaced circumferentially around the torso of the animal subject to surround the organ tumor.

[0218] Embodiment 33B: The method of embodiment 31B, wherein the tumor is a subcutaneous tumor, and the plurality of openings are radially spaced from a hole extending through the treatment assembly, the hole receiving at least a portion of the subcutaneous tumor.

[0219] Aspect 34B: The method of aspect 33B, further comprising the steps of placing a cap over the subcutaneous tumor and securing the cap to a cover layer of the treatment assembly.

[0220] Aspect 35B: The method of any one of aspects 31B to 34B, wherein the step of using an electrical signal generating device to generate an electrical signal includes the step of sequentially generating a first electrical signal and a second electrical signal, and the step of using at least a portion of the electrodes of the treatment assembly to generate an electric field from the electrical signals includes the step of using a first electrode and a second electrode to generate a first electric field across the tumor from the first electrical signal, and the step of using a third electrode and a fourth electrode to generate a second electric field across the tumor from the second electrical signal.

[0221] Embodiment 36B: The method of embodiment 35B, wherein the first electric field and the second electric field each have an axis of propagation, and the axis of propagation of the first electric field intersects the axis of propagation of the second electric field.

[0222] Embodiment 37B: The method of any one of embodiments 28B to 36B, wherein the step of using an electrical signal generating device to generate an electric field includes generating an electric field at a frequency between 50 kHz and 500 kHz.

[0223] Embodiment 38B: The method of any one of embodiments 31B to 37B, wherein the animal subject is a member of an experimental group, and the method includes the steps of electrically coupling at least a portion of an electrode of a control heating device of any one of embodiments 39B to 42B to an electrical signal generating device; attaching the control heating device to a second animal subject having a tumor, wherein the second animal subject is a member of the control group, and wherein a heater of the second treatment assembly surrounds at least a portion of the tumor; and using the electrical signal generating device to generate heat through the heater of the control heating device, wherein at least a portion of the electrodes of the second treatment assembly conduct heat through a corresponding plate of the plurality of plates, and wherein the heat generated by the control heating device mimics the heat generated by the first treatment assembly during delivery of the electric field.

[0224] Embodiment 39B: A control heating device comprising a circuit comprising a plurality of zones arranged in a spaced apart configuration matching the configuration of the plurality of electrodes of a treatment assembly as in any of embodiments 1B to 27B, at least one heater disposed in each of the plurality of zones, at least one temperature sensor, and a cable in communication with the at least one heater and the at least one temperature sensor of the circuit.

[0225] Embodiment 40B: The control heating device of embodiment 39B, wherein the at least one temperature sensor comprises a plurality of temperature sensors, each temperature sensor of the plurality of temperature sensors being disposed in a respective zone of the plurality of zones.

[0226] Embodiment 41B: A control heating device of embodiment 39B or embodiment 40B, wherein the circuitry and cable are integrally constructed as a flexible printed circuit board.

[0227] Embodiment 42B: A control heating device of any one of embodiments 39B to 41B, further comprising an inner layer having an upper surface and a plurality of openings, each of the zones being disposed within an opening of the plurality of openings, and a cover layer extending over the upper surface of the inner layer.

[0228] Embodiment 43B: A treatment assembly of any one of embodiments 1B to 27B, wherein the plurality of electrodes comprises a plurality of head electrodes configured to be placed on the head of the test subject and a plurality of torso electrodes configured to be placed on the torso of the test subject.

[0229] Embodiment 44B: The treatment assembly of embodiment 43B, wherein the treatment circuit comprises a serpentine portion extending from the multiple torso electrodes to the multiple head electrodes.

[0230] Embodiment 45B: A treatment assembly of embodiment 43B or embodiment 44B, wherein the plurality of head electrodes comprises a first group of electrodes arranged on a first side relative to the median plane and a second plurality of electrodes arranged on a second side opposite the first side relative to the median plane, and the plurality of torso electrodes comprises at least a first torso electrode arranged on the first side and at least a second torso electrode arranged on the second side.

[0231] Aspect 1C: A pivot assembly having a longitudinal axis, comprising an upper portion, a lower portion rotatably coupled to the upper portion, the lower portion having a connector configured to securely engage a cable and configured to remain in electrical communication with the upper portion when rotated relative to the upper portion, a motor positioned between the upper and lower portions and configured to selectively rotate the lower portion, a sensor configured to detect a twist in the cable, and a controller in communication with the sensor and the motor, wherein the controller is configured to rotate the motor in a direction corresponding to a direction of twist in the cable upon receiving a signal from the sensor indicating a threshold twist in the cable.

[0232] Embodiment 2C: The pivot assembly of embodiment 1C, wherein the connector on the lower portion is an electrical connector, the electrical connector configured to securely engage an electrical cable.

[0233] Embodiment 3C: The pivot assembly of embodiment 2C, wherein the electrical connector is configured for electrical communication with the electrical signal generating device and is further configured to allow electrical communication between the electrical signal generating device and the electrical cable.

[0234] Embodiment 4C: The pivot assembly of any one of Embodiments 1C to 3C, wherein the control device is configured to rotate the motor in a direction corresponding to the twist direction of the cable until a signal is received from the sensor indicating that the twist in the cable has fallen below a second threshold.

[0235] Aspect 5C: The swivel assembly of any one of Aspects 1C to 4C, further comprising a mounting assembly attached to an upper portion of the swivel relative to the longitudinal axis, the lower portion of the swivel being rotatably connected to the mounting assembly via the upper portion of the swivel.

[0236] Embodiment 6C: The pivot assembly of embodiment 5C, wherein the mounting assembly is configured to be secured to an upper surface of the cage.

[0237] Embodiment 7C: The swivel assembly of embodiment 5C or embodiment 6C, wherein the mounting assembly defines an opening in communication with the cable exit.

[0238] Embodiment 8C: The pivot assembly of any one of embodiments 1C to 7C, wherein the lower portion includes a base plate below and engaging the motor, the motor providing a rotational force to the lower portion through the base plate.

[0239] Embodiment 9C: The pivot assembly of any one of embodiments 1C to 8C, wherein the upper portion includes a support plate that covers the motor.

[0240] Embodiment 10C: The pivot assembly of any one of embodiments 1C to 9C, wherein the upper portion further comprises a vibration damping plate covering the motor.

[0241] Embodiment 11C: A rotation assembly of any one of embodiments 1C to 10C, wherein the control device is configured to detect abnormal rotation of the rotation assembly, the abnormal rotation being detected by at least one of (1) one or more signals from the sensor indicating a frequency of change in rotational direction exceeding a frequency threshold, and (2) one or more signals from the sensor indicating continuous rotation in a single rotational direction exceeding a time threshold.

[0242] Embodiment 12C: The pivoting assembly of embodiment 11C, wherein the controller is configured to receive user input to define at least one of the frequency threshold and the time threshold.

[0243] Embodiment 13C: The pivot assembly of embodiment 11C or embodiment 12C, further comprising a warning indicator, wherein the controller is configured to activate the warning indicator upon detecting abnormal rotation.

[0244] Embodiment 14C: The pivot assembly of embodiment 13C, wherein the warning indicator comprises at least one of a visible indicator and an audible indicator.

[0245] Aspect 15C: The pivot assembly of any one of Aspects 1C to 14C, wherein the sensor is a torque sensor comprising a pivot body pivotably coupled to a lower portion of the pivot section about a pivot axis and coupled to the cable such that twisting of the cable applies a torque to the pivot body causing pivoting of the pivot body relative to the lower portion of the pivot section, the pivot body having a radially extending surface extending radially outward relative to the pivot axis, a spring configured to bias the pivot body toward a neutral position relative to the lower portion of the pivot section, and first and second electro-optical sensors radially spaced from the pivot axis of the pivot body at respective angular positions relative to the pivot body, wherein the radially extending surface of the pivot body is configured to cause a change in state in the first electro-optical sensor when the pivot body pivots a first threshold angular distance in a first direction from the neutral position, and wherein the radially extending surface of the pivot body is configured to cause a change in state in the second electro-optical sensor when the pivot body pivots a second threshold angular distance in an opposite second direction from the neutral position.

[0246] Embodiment 16C: The pivot assembly of embodiment 15C, further comprising a printed circuit board having a first portion rotatably fixed to a lower portion of the pivot portion, a second portion pivotable with the pivot body, and at least one notch such that the printed circuit board has a patterned portion that allows the first portion to pivot relative to the second portion.

[0247] Example 17C: A pivot assembly as in Example 15C or Example 16C, wherein each of the first and second electro-optical sensors comprises a light source, a light detector, and an optical path between the light source and the light detector, and wherein a radially extending surface of the pivot body is configured to obstruct a respective optical path of each of the first electro-optical sensor and the second electro-optical sensor when the pivot body is in a neutral position, and a change of state in the first electro-optical sensor due to the pivot body pivoting a first threshold angular distance in a first direction from the neutral position includes the first electro-optical sensor no longer detecting the radially extending surface that obstructs the optical path of the first electro-optical sensor.

[0248] Embodiment 18C: A swivel assembly as in embodiment 17C, wherein the radially extending surface of the pivot body comprises a protrusion.

[0249] Embodiment 19C: The pivot assembly of any one of embodiments 1C to 18C, wherein the motor is a brushless gimbal motor.

[0250] Embodiment 20C: The pivot assembly of any one of embodiments 1C to 19C, further comprising a cable having a proximal end portion secured to the connector and an opposite distal end, the cable configured to move in response to application of a force to the distal end portion of the cable.

[0251] Embodiment 21C: The pivot assembly of any one of Embodiments 1C to 20C, further comprising a slip ring configured to provide electrical communication between the upper portion and the lower portion when the lower portion rotates relative to the upper portion.

[0252] Embodiment 22C: The swivel assembly of any one of embodiments 1C to 21C, wherein the cable is a portion of a flexible printed circuit board.

[0253] Embodiment 23C: A method comprising: fixing a proximal end portion of a cable to a connector of a pivot assembly of any one of embodiments 1C to 22C; and, in response to a twist in the cable in the first direction, using a control device to rotate a motor in a direction responsive to the first direction of twist in the cable.

[0254] Embodiment 24C: The method of embodiment 23C, wherein the cable is an electrical cable, the cable having a distal end portion electrically coupled to the electrode array.

[0255] Embodiment 25C: The method of embodiment 24C, wherein the electrode array is coupled to an animal subject.

[0256] Embodiment 26C: The method of embodiment 25C, wherein the animal subject is placed in a cage and the swivel assembly is secured to the cage.

[0257] Aspect 27C: The method of any one of aspects 23C to 26C, further comprising using the control device to determine abnormal rotation based on at least one of: (1) one or more signals from the sensor indicating a frequency of change in rotational direction exceeding a frequency threshold; and (2) one or more signals from the sensor indicating continuous rotation in a single rotational direction exceeding a time threshold.

[0258] Aspect 28C: A system comprising: a pivoting assembly as in any one of aspects 1C to 22C; and a computing device having a memory device in communication with at least one processing device, the memory device including instructions that when executed cause the at least one processing device to perform a method including storing in the memory device at least one metric selected from the group consisting of: number of rotations, number of rotations in a first selected period of time, frequency of motor motion, frequency of motor motion in a second selected period of time, number of motor motions including changes in direction, number of motor motions in the second selected period of time including changes in direction, duration of constant motion, and a log of motor motions and corresponding times of motor motions.

[0259] Aspect 29C: The pivot assembly of aspect 28C, wherein the storage device includes instructions that, when executed, cause the at least one processing device to perform a method further including generating a log report including the at least one metric.

[0260] Embodiment 30C: The pivot assembly of embodiment 29C, wherein the log report further includes at least one comparison of the at least one metric and an average of the at least one metric over a particular period of time.

[0261] Embodiment 1D: A system comprising a cage assembly of any one of embodiments 1A to 32A and a swivel assembly of any one of embodiments 1C to 22C.

[0262] Embodiment 2D: The system of embodiment 1D, further comprising any one of the treatment assemblies of embodiments 1B to 27B.

[0263] Embodiment 3D: The system of embodiment 1D, further comprising a control heating device of any one of embodiments 39B to 42B.

[0264] Aspect 4D: A method of using the system of any one of aspects 1D to 3D.

[0265] Although the foregoing invention has been described in some detail by way of illustration and example, for purposes of clarity of understanding, certain changes and modifications may be practiced within the scope of the appended claims. [Explanation of symbols]

[0266] 1 inner adhesive wearable layer, 2 hydrogel portion, 3 ceramic plate, 4 inner adhesive patch, 5 flexible circuit board, 6 head wearable layer, 7 outer wearable layer, 8 circuit board edge, 9a head covering portion, 9b torso covering portion, 10 system, 12 test subject, signal generator, 16 corner, 18 TTFields generator, 20 second cable, 60 first axis of propagation, 100 cage assembly, 102 main body, 104 floor, 108 side walls, 108A front wall, 108B rear wall, 108C side wall, 110 corner, 112 door, 114 hinge, 120 cover, 122 latch portion, 124 hinge, 126 latch portion, 128 hinge, 130 opening, 132 filter, 134 frame, 136 Nut, 138 Bolt, 140 Partition, 142 First Enclosure, 144 Second Enclosure, 146 Opening, 150 Shelter Subassembly, 178 Cover Assembly, 180 Swivel Housing, 182 Side Wall, 184 Internal Circumferential Insert, 186 Top Cover, 200, 200', 200" TTFields Therapy Assembly, 201 Longitudinal Dimension, Longitudinal Axis, 202, 202' Circuit Board, 204, 204' Cable, 205 Electrical Leads, 206, 206' Connector Ends, 208, 208' Lead Ends, 210, 210' Plate, 212, 212' Inner Layer, 214 Outer Surface, 216 Inner Surface, 218, 218' Opening, 220 Upper Surface, 222 Lower surface, 224, 224' hydrogel layer, 230, 230' cover layer, 232 tab portion, 250, 250' release layer, 252, 252' tab, 260 temperature sensor, 270' through hole, 272' cap, 274' receiving portion, 276' periphery, flange, 278' adhesive ring, 300 pivot assembly, pivot portion, 302 damping plate, 304 motor mounting plate, 306 screw, 314 base, 316 screw, bearing housing,Pivot, 318; Standoff, 320; Dependent tab, 322; Circuit assembly, 324; Printed circuit board, 326; Input / output connector, 328; Patterned portion, 330; Base portion, 332; Cable connector end, 334; Sensor connector portion, 340; Bearing, 342; Pivot, 344; Slot, 346; Tab, 350; Standoff, 352; Protrusion, 354; Neutral position, 356; Sensor, 356A; First sensor, 356B; Second optical sensor, 358; Sensor mounting portion, 359; Circuit board, PCB, 364; Restriction portion, 380; Connector, 400, 400'; Control heater treatment assembly, 402, 402'; Flexible circuit board, 404; Cable, 406, 406'; Connector end, 410; Hydrogel, zone, 412 plate, resistive heater, 414, 414' temperature sensor, 416 hydrogel, 420, 420' inner layer, 430, 430' cover layer, cover liner, 440, 440' release liner, 450' cap, 500 annulus, 502 projection, 504 hole, 506 first end, 508 second end, 510 inner surface, 512 outer surface, 602, 602a, 602b electrode, 604 electrode, 606 median surface, 700 alternating shaped portion, 1000 system, 1001 computing device, 1002 human machine interface, 1003 processing device, 1004 mass storage device, 1005 operating system, 1006 TTField delivery software, electrode data processing software, 1007 temperature data, 1008 network adapter, 1009 Display adapter, 1010 input / output interface, 1011 display device, display unit, 1012 system storage device, 1013 bus, 1014a, 1014b, 1014c computer device, 1015 network, D distance, d spacing, h cage height, R1 enclosure length, R2 enclosure width, t cage floor threshold distance,

Claims

1. an inner layer having an inner surface and an outer surface, the inner layer defining a plurality of apertures extending therethrough; a plurality of plies each at least partially received within a respective one of the plurality of openings in the inner layer; A therapeutic circuit comprising: a cable having a plurality of electrical leads; and a plurality of lead ends, each electrical lead being electrically connected to a respective one of the plurality of lead ends; A treatment circuit comprising: a cover layer attached to the outer surface of the inner layer and covering the ends of the leads of the cable, the inner layer and the cover layer cooperating to form a hole through the treatment assembly, the hole receiving a subcutaneous tumor therethrough; a cap extending across the hole and having a receiving portion formed therein configured to receive the subcutaneous tumor, the cap being attached to a cover layer; Equipped with A treatment assembly, wherein a plurality of said lead ends are in contact with respective plates of a plurality of said plates to define a plurality of electrodes, each electrode of the plurality of said electrodes comprising a respective lead end and a respective plate.

2. The treatment assembly of claim 1 , wherein at least one of the plurality of plates comprises a ceramic plate.

3. 10. The treatment assembly of claim 1, wherein at least one of the plurality of plates comprises a glass plate.

4. The treatment assembly of claim 1 , wherein at least one electrode of the plurality of electrodes is configured to generate an electric field through a corresponding plate of the plurality of plates.

5. 2. The treatment assembly of claim 1, wherein the electrodes of the treatment circuit have respective upper surfaces, and the cover layer extends over the upper surfaces of the electrodes of the cable.

6. 2. The treatment assembly of claim 1, wherein each of the plurality of plates has a lower surface and an opposing upper surface, the treatment assembly further comprising a layer of hydrogel on the lower surface of each of the plurality of plates.

7. The treatment assembly of claim 1 , wherein the treatment circuit further comprises at least one temperature sensor.

8. The treatment assembly of claim 1 , wherein the inner layer and the cover layer cooperate to define a hole therethrough, the hole being configured to receive a subcutaneous tumor therethrough.

9. 9. The treatment assembly of claim 8, further comprising a cap attached to the cover layer, the cap extending across the hole and defining a receiving portion therein configured to receive the subcutaneous tumor.

10. The treatment assembly of claim 8 , wherein a plurality of said plates are disposed radially outward of said hole defined through said treatment assembly.

11. 10. The treatment assembly of claim 9, wherein the cap comprises a rim, the treatment assembly further comprising an adhesive ring covering the rim and securing the cap to the cover layer.

12. The treatment assembly of claim 1 , wherein the treatment assembly has a longitudinal dimension in a pre-use configuration, the cover layer comprises a biocompatible non-woven adhesive, and the non-woven adhesive is elastic in the longitudinal dimension.

13. 13. The treatment assembly of claim 12, wherein in a use configuration, the cables extend perpendicular or substantially perpendicular to the longitudinal dimension.

14. 14. The treatment assembly of any one of claims 1 to 13, wherein the inner layer comprises a biocompatible, breathable polyurethane adhesive on the inner surface of the inner layer.

15. The treatment assembly of claim 14 , wherein the cover layer has an inner surface comprising a biocompatible non-woven adhesive.

16. 16. A treatment assembly according to any one of claims 1 to 15, wherein the plurality of electrodes comprises a plurality of electric field generating electrodes, the plurality of electric field generating electrodes configured to transmit an electric field through a corresponding one of the plurality of plates.

17. 17. The treatment assembly of claim 16, wherein the treatment circuit further comprises a plurality of thermistors.

18. 18. The treatment assembly of claim 17, wherein a respective electrode of the plurality of electrodes and a respective thermistor of the plurality of thermistors are in communication with each plate of the plurality of plates.

19. The treatment assembly of claim 1 , wherein the treatment assembly weighs less than 2.5 grams.

20. The treatment assembly of claim 1, which is flexible enough to circumferentially conform to a portion of the torso of a non-human animal subject.

21. 2. The treatment assembly of claim 1, wherein the cable comprises an end connector disposed at an end of the cable opposite the plurality of electrodes, the end connector configured to allow connection of the cable to an electrical signal generating device.

22. 15. The treatment assembly of claim 14, further comprising a release layer in contact with the biocompatible, breathable polyurethane adhesive on the inner surface of the inner layer.

23. 23. The treatment assembly of claim 22, wherein the release layer has a shape that is complementary to a shape of the cover layer.

24. The treatment assembly of claim 1 , wherein the cover layer defines at least one tab portion extending beyond the inner layer.

25. 25. The treatment assembly of claim 24, wherein at least one said tab portion comprises two opposing tab portions that are complementary to one another when the cover layer defines a circumferential hoop.

26. The treatment assembly of claim 1 , wherein the plurality of apertures comprises a plurality of longitudinally spaced apertures.

27. The treatment assembly of claim 1 , wherein the treatment circuit and the cable are integrally constructed as a flexible printed circuit board.

28. 2. The treatment assembly of claim 1, wherein the plurality of electrodes comprises a plurality of head electrodes configured to be placed on a head of a test subject and a plurality of torso electrodes configured to be placed on a torso of the test subject.

29. The therapy circuit includes a serpentine portion extending from a plurality of the torso electrodes to a plurality of the head electrodes.

30. The treatment assembly of claim 28.

30. 29. The treatment assembly of claim 28, wherein the plurality of head electrodes comprises a first group of electrodes disposed on a first side relative to the median plane and a second plurality of electrodes disposed on a second side opposite the first side relative to the median plane, and the plurality of torso electrodes comprises at least a first torso electrode disposed on the first side and at least a second torso electrode disposed on the second side.

31. 31. A method of making a therapeutic assembly according to any one of claims 1 to 30, comprising the steps of: placing a plurality of said plates into respective openings in said inner layer of said treatment assembly; placing each electrode of a plurality of said electrodes of said treatment circuit in contact with a plate of a plurality of said plates; attaching the cover layer to the outer surface of the inner layer, the cover layer covering the electrodes of the treatment circuit; The method includes:

32. 32. The method of claim 31, further comprising applying a layer of hydrogel to an underside of each of the plurality of plates.

33. 33. The method of claim 32, wherein the lower surfaces of at least two of the plurality of plates share a layer of hydrogel.

34. At least one treatment assembly according to any one of claims 1 to 30; an electrical signal generator in communication with the treatment assemblies, the electrical signal generator configured to generate an electric field through at least one of the treatment assemblies; A system comprising:

35. 35. The system of claim 34, wherein in a pre-use configuration, the plurality of openings and the plurality of plates are longitudinally spaced along a longitudinal axis of the treatment assembly, and in a use configuration, the plurality of openings and the plurality of plates are circumferentially spaced around the torso of a non-human animal subject to surround an organ tumor.

36. 35. The system of claim 34, wherein the plurality of openings are radially spaced from a hole extending through the treatment assembly, the hole configured to receive at least a portion of a subcutaneous tumor.

37. 37. The system of claim 36, wherein the treatment assembly comprises a cap configured to be placed over the subcutaneous tumor, the cap being secured to the cover layer of the treatment assembly.

38. the electrical signal generator is configured to sequentially generate a first electrical signal and a second electrical signal, and a first electrode and a second electrode of the plurality of electrodes are configured to generate a first electric field across a tumor from the first electrical signal; 35. The system of claim 34, wherein a third electrode and a fourth electrode of the plurality of electrodes are configured to generate a second electric field across the tumor from the second electrical signal.

39. 40. The system of claim 38, wherein the first electric field and the second electric field each have an axis of propagation, and the axis of propagation of the first electric field intersects the axis of propagation of the second electric field.

40. 35. The system of claim 34, wherein the electrical signal generator is configured to generate an electrical signal at a frequency between 50 kHz and 500 kHz.

41. A plurality of zones arranged in a spaced apart configuration matching the configuration of the plurality of electrodes of a treatment assembly according to any one of claims 1 to 30; at least one heater disposed in each of the plurality of zones; At least one temperature sensor; a cable in communication with at least one of the heaters and at least one of the temperature sensors in a circuit; 35. The system of claim 34, further comprising at least one control heating device comprising a circuit comprising:

42. 42. The system of claim 41, wherein the at least one temperature sensor comprises a plurality of temperature sensors, each temperature sensor of the plurality of temperature sensors disposed in a respective one of the plurality of zones.

43. 42. The system of claim 41, wherein the circuitry and the cable of at least one of the control heating devices are integrally constructed as a flexible printed circuit board.

44. At least one of the control heating devices an inner layer having an upper surface and including a plurality of openings, each of the zones being disposed within an opening of the plurality of openings; a cover layer extending over the upper surface of the inner layer; 42. The system of claim 41, further comprising:

45. Electrically coupling at least a portion of the electrodes of the treatment assembly according to any one of claims 1 to 30 to an electrical signal generating device; attaching the treatment assembly to a non-human animal subject having a tumor, the plate of the treatment assembly surrounding at least a portion of the tumor; using the electrical signal generator to generate an electrical signal; using at least the portion of the electrodes of the treatment assembly to generate an electric field from the electrical signal through a corresponding one of the plurality of plates; The method includes:

46. 46. ​​The method of claim 45, wherein the tumor is an organ tumor, and wherein in a pre-use configuration, the plurality of openings and the plurality of plates are longitudinally spaced along a longitudinal axis of the treatment assembly, and in a use configuration, the plurality of openings and the plurality of plates are circumferentially spaced around the torso of the non-human animal subject to surround the organ tumor.

47. 46. ​​The method of claim 45, wherein the tumor is a subcutaneous tumor, and wherein the plurality of openings are radially spaced from a hole extending through the treatment assembly, the hole receiving at least a portion of the subcutaneous tumor.

48. 48. The method of claim 47, further comprising the steps of placing a cap over the subcutaneous tumor and securing the cap to the cover layer of the treatment assembly.

49. The step of using the electrical signal generator to generate the electric field includes the step of sequentially generating a first electric field and a second electric field, and the step of using at least the portion of the electrodes of the treatment assembly to generate the electric field from the electrical signal includes: using a first electrode and a second electrode to generate a first electric field across the tumor from a first electrical signal; using a third electrode and a fourth electrode to generate a second electric field across the tumor from the second electrical signal; 46. ​​The method of claim 45, comprising:

50. 50. The method of claim 49, wherein the first electric field and the second electric field each have an axis of propagation, and the axis of propagation of the first electric field intersects the axis of propagation of the second electric field.

51. 46. ​​The method of claim 45, wherein using the electrical signal generator to generate an electrical signal includes generating the electrical signal at a frequency between 50 kHz and 500 kHz.

52. The non-human animal subject is a member of an experimental group, and the method comprises: electrically coupling the electrodes of the control heating device to an electrical signal generating device; attaching the control heating device to a second non-human animal subject having a tumor, the second non-human animal subject being a member of a control group, the control heating device comprising a heater surrounding at least a portion of the tumor; using the electrical signal generating device to generate heat through a heater of the control heating device, where at least a portion of the electrodes of the control heating device conduct heat through a corresponding one of the plates; Further comprising:

46. ​​The method of claim 45, wherein the heat generated by the control heating device mimics the heat generated by the treatment assembly during delivery of the electric field.

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