Therapeutic assembly for providing a tumor treatment field to an animal test subject

Abstract

A therapy assembly can have an inner layer having an inner surface and an outer surface and defining a plurality of openings extending therethrough. The therapy assembly can also include a plurality of plates, each plate at least partially received within a respective opening of the plurality of openings of the inner layer. The therapy assembly can also include therapy circuitry including 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 be in contact with a respective plate of the plurality of plates to define a plurality of electrodes.

Description

[0001] Cross Reference to Related Applications

[0002] This application claims priority to and the benefit of the filing date 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 entire contents of both of which are incorporated herein by reference. TECHNICAL FIELD

[0003] The present invention relates to systems, devices, and methods for testing and using tumor treating fields (TTFields). The present disclosure includes descriptions of cage assemblies, treatment assemblies, and swivel joint systems for use with animal test subjects. BACKGROUND

[0004] A tumor treating field, or TTField, is a low intensity (e.g., 1-3 V / cm) alternating electric field in the intermediate frequency range (100-300 kHz). This non-invasive treatment targets solid tumors and is described in U.S. Patent No. 7,565,205, which is incorporated by reference herein in its entirety. TTFields disrupt cell division during mitosis through physical interactions with key molecules. TTField therapy is an approved monotherapy for recurrent glioblastoma, as well as an approved combination therapy with chemotherapy for newly diagnosed patients. These electric fields are non-invasively induced by a transducer array (i.e., electrode array) placed directly on the patient’s scalp. TTFields also appear to be beneficial in treating tumors in other parts of the body. Laboratory research has begun to test intermediate frequency alternating electric fields (tumor treating fields, or TTFields) in subcutaneous tumors and orthotopic tumors located in the torso of small animals (e.g., mice). SUMMARY

[0005] Described herein in various aspects is a treatment assembly including an inner layer having an inner surface and an outer surface. Optionally, the treatment assembly can be positioned on an animal test subject, which can optionally undergo TTField or control treatment. The inner layer can define a plurality of openings extending therethrough. The treatment assembly can further include a plurality of plates, each plate at least partially received within a respective opening of the plurality of openings of the inner layer. The treatment assembly can further include treatment circuitry including 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 be in contact with a respective plate of the plurality of plates to define a plurality of electrodes, each electrode of the plurality of electrodes including a respective lead end and a respective plate.

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

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

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

[0009] The plurality of electrodes of the therapy circuitry can have respective top surfaces. The cover layer can extend across the top surfaces of the cable electrodes.

[0010] Each of the plurality of plates has a lower surface and an opposite upper surface. The therapy assembly can further include a hydrogel layer on the lower surface of each of the plurality of plates.

[0011] The therapy circuitry can further include at least one temperature sensor.

[0012] The inner layer and the cover layer can cooperate to define a bore through the therapy assembly. The bore can be configured to receive a subcutaneous tumor therethrough.

[0013] The therapy assembly can further include a cap extending across the bore and defining a receptacle therein configured to receive the subcutaneous tumor. The cap can be affixed to the cover layer.

[0014] The plurality of plates can be located radially outward of the bore defined through the therapy assembly.

[0015] The cap can include an outer peripheral rim. The therapy assembly can further include an adhesive ring covering the outer peripheral rim and securing the cap to the cover layer.

[0016] In a pre-use configuration, the therapy assembly can have a longitudinal dimension. The cover layer can include a biocompatible nonwoven adhesive. The nonwoven adhesive can be elastic in the longitudinal dimension.

[0017] In a use configuration, the cable can extend perpendicular or substantially perpendicular relative to the longitudinal dimension.

[0018] The inner layer can include a biocompatible air-permeable polyurethane adhesive located on an inner surface of the inner layer.

[0019] The cover layer can have an inner surface including a biocompatible nonwoven adhesive.

[0020] The plurality of electrodes can include a plurality of electric field generating electrodes. The plurality of electric field generating electrodes can be configured to transmit an electric field through a corresponding one of the plurality of plates.

[0021] The therapy circuitry can further include a plurality of thermistors.

[0022] Respective ones of the plurality of electrodes and respective ones of the plurality of thermistors can be in communication with each of the plurality of plates.

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

[0024] The treatment assembly can be sufficiently flexible to conform circumferentially to a portion of the torso of an animal test subject.

[0025] The cable can include an end connector on an end of the cable opposite the plurality of electrodes. The end connector can be configured to allow the cable to be connected to an electrical signal generator.

[0026] The treatment assembly can further include a release layer in contact with the biocompatible, air permeable polyurethane adhesive on the inner surface of the inner layer.

[0027] The release layer can be shaped complementary to the shape of the cover layer.

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

[0029] The at least one tab portion can include two opposing tab portions that complement each other when the cover layer defines a circumferential ring.

[0030] The plurality of openings can include a plurality of longitudinally spaced openings.

[0031] The treatment circuitry and the cable can be integrally constructed as a flexible printed circuit board.

[0032] A method of manufacturing a treatment assembly can include positioning a plurality of plates within respective openings of an inner layer of the treatment assembly, placing each electrode of a plurality of electrodes of treatment circuitry in contact with one of the plurality of plates, and affixing a cover layer to an outer surface of the inner layer. The cover layer can cover the plurality of electrodes of the treatment circuitry.

[0033] The method can further include applying a layer of hydrogel to a lower surface of each of the plurality of plates.

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

[0035] A method can include electrically coupling at least a portion of electrodes of a treatment assembly to an electrical signal generator and affixing the treatment assembly to an animal test subject having a tumor. The plates of the treatment assembly can enclose at least a portion of the tumor. The electrical signal generator can be configured to generate an electrical signal (e.g., an electrical potential). At least a portion of the electrodes of the treatment assembly can be configured to deliver the electrical signal through a corresponding one 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 longitudinally spaced along a longitudinal axis of the treatment assembly. In a use configuration, the plurality of openings and the plurality of plates can be circumferentially spaced around a torso of the animal test subject to enclose the organ tumor.

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

[0038] The method can further include positioning the cap on the subcutaneous tumor and securing the cap to the cover layer of the treatment assembly.

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

[0040] The first electric field and the second electric field can have respective propagation axes, the propagation axis of the first electric field can intersect the propagation axis of the second electric field.

[0041] Generating the electrical signal using the electrical signal generator can include generating the electrical signal at a frequency between 50 and 500 kHz. The electrical signal can correspond to an alternating current provided at a frequency between 50 and 500 kHz (or 150 kHz to 300 kHz or about 200 kHz) configured to generate a TTField as further disclosed herein.

[0042] The animal test subject can be a member of an experimental group. The method can further include electrically coupling at least a portion of an electrode of a control heating device to the electrical signal generator. The control heating device can be affixed to a second animal test subject having a tumor. The second animal test subject can be a member of a control group. The heater of the second treatment assembly can surround at least a portion of the tumor. The electrical signal generator can 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 can transfer the heat through a corresponding one of the plurality of plates. The heat generated by the control heating device can simulate heat generated by the first treatment assembly during electric field delivery.

[0043] The control heating device can include circuitry including a plurality of zones positioned in a configuration matching a configuration of the plurality of electrodes of the treatment assembly, at least one heater in each zone 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 circuitry.

[0044] The at least one temperature sensor can include a plurality of temperature sensors, wherein each temperature sensor of the plurality of temperature sensors is in each zone of the plurality of zones.

[0045] The circuitry and the cable can be integrally configured as a flexible printed circuit board.

[0046] The counter heating device can 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 these regions can be disposed within one of the plurality of openings.

[0047] Additional advantages of the application will be set forth in part in the description which follows, and in part will be obvious from the description, or can be learned by practice of the application. The advantages of the application 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 application, as claimed. BRIEF DESCRIPTION OF DRAWINGS

[0048] These and other features of the preferred embodiments of the present application will become more apparent from the following detailed description, taken in conjunction with the accompanying drawings, in which:

[0049] FIG. 1 is a system for testing TTField treatment according to embodiments disclosed herein.

[0050] FIG. 2 is a test subject to which a treatment assembly is attached.

[0051] FIG. 3 is an exploded view of a cage system according to embodiments of the present disclosure.

[0052] FIG. 4 is a front view of the cage system of FIG. 3

[0053] FIG. 5 is a side view of the cage system of FIG. 3

[0054] FIG. 6 is a schematic view of a test subject inside the cage system of FIG. 3 , approximating a cross-section taken in a plane P of FIG. 5

[0055] FIG. 7 is a schematic view showing measurements inside the enclosure of the cage system of FIG. 3

[0056] FIG. 8 is an exploded view of a treatment assembly for use with a system as in FIG. 1

[0057] FIG. 9 is an exploded view of another treatment assembly for use with a system as in FIG. 1 ​​​​​​

[0058] FIG. 10A is an exploded view of a counter-heater assembly according to embodiments disclosed herein. FIG. 10B is FIG. 10A is a portion of a circuit board of the counter-heater assembly of

[0059] FIG. 11A is an exploded view of another counter-heater assembly according to embodiments disclosed herein. FIG. 11B is FIG. 11A is a portion of a circuit board of the counter-heater assembly of

[0060] FIG. 12A is a partial exploded view of a cage according to embodiments disclosed herein, showing positioning of a rotary joint relative to an associated cage assembly. FIG. 12B is FIG. 12A is a detailed view of a rotary joint of

[0061] FIG. 13 is FIG. 12B is a side view of a circuit board of the rotary joint assembly of

[0062] FIG. 14 is FIG. 13 is a transparent view of a circuit board of

[0063] FIG. 15 is FIG. 12B is an exploded view of a rotary joint of

[0064] FIG. 16 is FIG. 12B is a side view of a rotary joint of

[0065] FIG. 17 is FIG. 12B is a bottom side view of a rotary joint of

[0066] FIG. 18A is FIG. 12B is a perspective view of a rotary joint of FIG. 18B is FIG. 18A is a detailed perspective view of a portion of a rotary joint of

[0067] FIG. 19 is a perspective view of a rotary joint portion as in FIG. 18B is a perspective view of a rotary joint portion as in

[0068] FIG. 20 is a schematic view of a therapy assembly for providing therapy to an organ tumor according to embodiments disclosed herein.

[0069] FIG. 21is a schematic view of a treatment assembly for providing therapy to a subcutaneous tumor in accordance with embodiments disclosed herein.

[0070] FIG. 22 is a schematic view of a system in use with a computing device of FIG. 1

[0071] FIG. 23 is an exploded view of an embodiment of a swivel joint and its housing.

[0072] FIG. 24 is an exploded view of an exemplary treatment assembly.

[0073] FIG. 25 is a top view of an exemplary treatment assembly as in FIG. 24

[0074] FIG. 26 is a perspective view of a treatment assembly of FIG. 24 positioned on a test subject.

[0075] FIG. 27 is a top view of a treatment assembly of FIG. 24 positioned on a test subject.

[0076] FIG. 28 is a top view of a treatment assembly of FIG. 24 showing communication between electrodes.

[0077] FIG. 29 is a top view of a treatment assembly of FIG. 24 showing alternating profile portions.

[0078] FIG. 30 is a side view of a collar in accordance with embodiments disclosed herein.

[0079] FIG. 31 is a side view of a collar of FIG. 30

[0080] is a top view of a collar of FIG. 32 FIG. 30 DETAILED DESCRIPTION

[0081] The present application will now be described more fully hereinafter with reference to the accompanying drawings, in which some, but not all embodiments of the applications are shown. Indeed, the applications can be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will satisfy applicable legal requirements. Like numbers refer to like elements throughout. It will be understood that the applications are not limited to the particular methodologies, protocols, and reagents described, as these can vary. It will be further understood that the terms used herein are for the purpose of describing particular embodiments and are not intended to limit the scope of the present applications.​​​​

[0082] Those of skill in the art will appreciate that the invention described herein is susceptible to many modifications and other embodiments based on the teachings and principles of the present description. As such, it will be understood that the invention is not limited to the particular embodiments disclosed and that modifications and other embodiments are intended to be included within the scope of the appended claims. Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation.

[0083] As used herein, the singular forms "a", "an" and "the" include plural referents unless the context clearly dictates otherwise.

[0084] Unless specifically indicated otherwise, 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.

[0085] As used herein, the term "optional" or "optionally" means that the subsequently described event or circumstance can or can not occur, and that the description includes instances where the event or circumstance occurs and instances where it does not.

[0086] As used herein, the term "at least one of" is intended to mean one or more of the listed items can be present and, further that when there is more than one of each of the items, that either a single reference to the item or a plural reference is appropriate, depending on context. For example, the phrase "at least one of A and B" covers A alone, B alone, or A and B.

[0087] Ranges can be expressed herein as from "about" one particular value, and / or to "about" another particular value. When such ranges are expressed, another aspect includes from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations by using antecedent terms such as "about," it will be understood that the particular value forms another aspect. It will be further understood that each endpoint is significantly independent of the other, with neither endpoint being significantly dependent on the other. Optionally, in some aspects, when values are approximated by using antecedent terms such as "about," it is contemplated that values within 15% of the particular stated value, within 10% of the particular stated value, within 5% of the particular stated value, or within 1% of the particular stated value are included in the range. Similarly, the use of "substantially" (e.g., "substantially parallel") or "approximately" (e.g., "approximately planar") should be understood as including embodiments within about ten degrees, or within about five degrees, or within about one degree of the particular angle.

[0088] As used herein, the word "or" means any one member of a particular list and also includes any combination of the members of that list.

[0089] It will be understood that, unless otherwise specifically stated, no method described herein is intended to require its steps to be performed in a particular order, and nothing in the description of a method should be interpreted as requiring its steps to be performed in an order other than that which is actually recited in the method claim. Thus, where a method claim does not actually recite an order to be followed by its steps or it is otherwise explicit in the claim that maintaining the order is not a requirement, no inference should be drawn that as to any suggest order to the steps. This holds true for any possible non- explicitly recited aspects of the methods, including but not limited to the recitation of logical steps in the process flow, the recitation of logical steps in the description of the method claim, and the recitation of logical steps in the specification.

[0090] In the following description and claims, whenever a word "comprise" or "comprising" is used, it shall be understood that the word "comprise" and "comprising" are not used in the sense of the word "consist of or "consisting of" to limit the items listed to only include those items.

[0091] The following description provides specific details for the purpose of providing a thorough understanding. However, a person of ordinary skill in the art will recognize that the devices, systems, and associated methods of using the devices can be practiced without employing these specific details. Indeed, the devices, systems, and associated methods can be practiced by modifying the illustrated devices, systems, and associated methods, and by employing any other devices and techniques conventionally used in the industry.

[0092] TTFields (also referred to herein as alternating electric fields) were established as an anti-mitotic cancer treatment modality because they interfere with proper microtubule assembly during metaphase and ultimately destroy cells during anaphase and cytokinesis. Therapeutic efficacy increases with increasing field strength and the optimal frequency is cancer cell line dependent, with 200 kHz being the highest frequency for the inhibition of glioma cell growth caused by TTFields. For cancer treatment, a non-invasive device was developed utilizing capacitively coupled transducers placed directly on the skin area close to the tumor. For patients with glioblastoma multiforme (GBM), the most common primary, malignant brain tumor in humans, the system for delivering TTFields therapy is called the OPTUNE™ system (Novocure Ltd.).

[0093] Because the effect of a TTfield is directional, with cells dividing parallel to the field split being more greatly affected than cells dividing in other directions, and because cells divide in all directions, a TTfield is typically delivered by two pairs of transducer arrays that generate perpendicular fields within the tumor being treated. More specifically, for the OPTUNE system, one pair of electrodes is positioned on the left and right sides of the tumor (LR), and another pair of electrodes is positioned on the front and back sides of the tumor (AP). Cycling the field between these two directions (i.e., LR and AP) ensures targeting the maximum range of cell orientation.

[0094] Although TTFields have been approved for use in certain patients, there remains a need for systems that allow 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 otherwise damages the electrical components. Additionally, when the animal is tethered using a cable, the animal often causes twisting of the cable. When too much slack is provided in such a cable, the animal can easily roll over, causing the electrical components to be damaged or positioned incorrectly. When not enough slack is provided in such a cable, the animal’s movements can be too restricted. Further, it can be difficult to couple electrical components to the animal without significant adjustment and repositioning.

[0095] In various aspects and with reference to FIG. 1 , disclosed herein is a system 10 for providing TTFields to test subjects 12 (e.g., animal test subjects, such as mice). The system 10 can include one or more cage assemblies 100 to receive and house one or more test subjects. Some test subjects in an experimental group 14 can be fitted with a TTField treatment assembly 200, 200’, 200” (described below) FIG. 8 、 FIG. 9 and FIG. 24 that can include a transducer array for providing treatment to the test subject. Other test subjects in a control group 16 can be fitted with a control heater treatment assembly 400, 400’ (described below) FIG. 10A-11B), which is configured to provide the same weight and heat as the TTField treatment assembly 200, 200', 200". The plurality of TTField treatment assemblies 200, 200', 200" can be communicatively coupled to the TTField generator 18. Optionally, the TTField generator can be the generator provided as part of the INOVITRO laboratory research system (NOVOCURE GMBH). Similarly, the plurality of control heater treatment assemblies 400 can be communicatively coupled to the same or separate TTField generator 18 (or other generator capable of initiating heat through the control heater treatment assemblies, as further disclosed herein). The computer 1001 can be communicatively coupled to the TTField generator 18. The computer 1001 can control the output of the TTField generator(s) 18, as well as log data from the TTField generator 18, treatment assemblies 200, 200', 200", control heater treatment assemblies 400, and / or the test subject 12.

[0096] The TTField treatment assemblies 200, 200', 200" and control heater treatment assemblies 400 can communicate with the TTField generator 18 via respective cables 204 FIG. 8 ). To enable the test subject to move freely within the cage assembly 100 without entangling the cables 204, the cables 204 can extend to and be coupled to a swivel 300 (also referred to herein interchangeably as a swivel assembly 300). The swivel 300, in turn, can be coupled to a second cable 20 that extends to and is coupled to the TTField generator 18. Thus, as further disclosed herein, the swivel 300 can enable electrical communication from the TTField generator 18, through the second cable 20, through the swivel assembly 300, to the cables 204 for communication with the treatment assemblies 200, 200', 200", while preventing entanglement of the cables 204.

[0097] Cage assembly

[0098] Reference is made to FIG. 3-5The cage assembly 100 can include a main body 102. The main body 102 can include a floor 104 defining a floor area having a major dimension. Optionally, the floor 104 can be rectangular or generally rectangular and have corners 16. Optionally, the corners 16 can be rounded. The corners can have a radius of, for example, about 17 mm. The major dimension can be the largest diagonal between the corners 106 of the cage. The main body 102 can further include one or more side walls 108. For example, the main body 102 can include a front side wall 108A, an opposite rear side wall 108B, and a pair of opposite side walls 108C extending between respective edges of the front and rear side walls 108A, 108B. The intersection between respective side walls can define rounded corners 110. Optionally, the side walls 108 can converge in a direction toward the floor 104 (i.e., extend inwardly inclined in a downward direction) to provide a draft angle for manufacturing via injection molding. Optionally, the floor can include litter as is commonly used in conventional animal cages. The litter can be, for example, sawdust. Food pellets can be placed on the floor of the enclosure for foraging. Conventional water bottles can be attached to the cage for the subjects to replenish water. Optionally, the cage can include an opening in the side wall of each enclosure to receive a dispensing portion of a conventional water bottle.

[0099] In example aspects, and as shown in FIG. 3 , the side walls 108 can define a plurality of apertures 130 for ventilation. One or more filters 132 can optionally cover the plurality of apertures in each side wall 108. A frame 134 can extend around the perimeter of the filter 132 and receive fasteners (e.g., a nut 136 and a bolt 138) to attach to the main body 102 of the cage assembly 100. In this way, the cage assembly is sealed such that all or substantially all ventilation to each enclosure travels through at least one filter before entering the ventilation opening. Optionally, as shown in FIG. 3 , a single filter 132 can cover the plurality of apertures 130 (optionally, all of the apertures) of the side wall 108. The filter can be removable, autoclavable, and replaceable. The filter can minimize the penetration of infectious agents and infectious bodies while enabling rapid air exchange. It is contemplated that a mesh, screen, grate, air-permeable membrane, or other permeable structure can be positioned between the plurality of apertures 130 and the filter 132 in the cage to discourage the subjects from chewing on the filter.

[0100] As shown in FIG. 3As shown in the middle, the door 112 can be pivotably coupled to the body portion 102 by a pair of hinges 114. In use, the door 112 can be movable about and between (1) a closed position in which the door 112 cooperates with the side walls to provide the enclosure(s), 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.

[0101] The cover 120 can extend across the top of the body 102. The cover 120 can be releasably attached to the body 102 via a latch 122. The latch 122 can be pivotably attached to the body 102 via a hinge 124. A latch 126 that is pivotable about a hinge 128 can be attached to the door 112. The latch 126 can releasably engage a catch on the top of the cover 120 for retaining the door 112 in the closed position. Optionally, the cover 120 can include one or more swivel joint housings 180 that are configured to receive at least a portion of a swivel joint, as further disclosed herein.

[0102] The partition 140 can define a common side wall that divides the interior of the cage into a first enclosure 142 and a second enclosure 144. The partition 140 can optionally be removable. The body can optionally define a slot into which the partition 140 can be inserted. The partition 140 can define an opening 146 (optionally, a plurality of openings) between the first enclosure 142 and the second enclosure 144 so as to allow respective test subjects 12 in each of the first and second enclosures to interact with one another (e.g., through acoustic interaction, through scent, through body warmth, etc.). Thus, the first enclosure 142 and the second enclosure 144 can each have respective side walls (or side wall portions) defined by the front side wall 108A, the door 112, the rear side wall 108B, the side wall 108C extending between the front and rear side walls, and the partition 140. In these examples, it is contemplated that the floor area within each enclosure can have a respective major dimension that can equal the largest diagonal between the corners of that enclosure.

[0103] The side walls (e.g., the body 104 and the partition 140) and the cover can optionally include polycarbonate and can optionally be autoclavable. Portions of the cage, such as, for example, the body 102 and the cover 120, can be transparent so that the test subjects can be observed when closed in the cage.

[0104] References FIG. 6The shelter subassembly 150 can extend inwardly from the partition 140 into each of the first enclosure 142 and the second enclosure 144. Within each enclosure, the shelter subassembly 150 can include an arcuate roof, a pair of parallel walls extending vertically downward from the arcuate 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 can project a selected distance D from the partition 140. Optionally, the distance D can be approximately 4-5 centimeters. It is contemplated that the distance D can be selected such that the cable will not restrict the test subject from interacting with the test subject of the opposing enclosure. For example, the cable can be tied to the back of the test subject at a selected spacing d away from the head of the test subject. In this manner, the test subject will not chew on the cable. The selected spacing can also enable the test subject to enter the shelter subassembly before the cable reaches the shelter subassembly. Further, the cable can be flexible enough to bend upon contact with the shelter subassembly. The selected distance that the shelter subassembly 150 projects from the partition 140 can be selected such that, when the cable is fully taut relative to the shelter subassembly, the test subject (e.g., at least the nose and / or face of the test subject) can reach at least a plane defined by the partition 140. As further disclosed herein, the cable length can be a function of the dimensions of the enclosure. Accordingly, the selected distance D that the shelter subassembly 150 projects from the partition 140 can be a function of the cable length and the height and width dimensions of the enclosure.

[0105] The covers 120 for the first and second enclosures can be integrally configured as a cover assembly 178. Optionally, the cover assembly 178 can include swivel joint housings 180. In these aspects, the cover assembly 178 can further include swivel joints 300, as further disclosed herein, positioned within respective swivel joint housings 180. The cover assembly 178 can include first and second openings between the first and second enclosures and their respective swivel joints 300. The first and second openings can provide communication to enable the cables of the treatment assembly to be coupled to the respective swivel joints. Each swivel joint can be in covering relationship with a respective one of the first and second openings. According to various aspects, each swivel joint can extend through a respective opening in the cover assembly and at least partially into a respective enclosure to receive a respective cable. In further embodiments, each cable can extend through a respective one of the first and second openings to be coupled to a respective swivel joint.

[0106] Reference is made to FIG. 4-7The distance between the cover 120 and the floor 104 can define a cage height. To prevent the test subject from having enough slack in the cable 204 to flip over or entangle with the cable, the cage assembly can have a selected cage height h that is a function of the length Rl and the 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 their body. According to some optional aspects, the dimensions of each enclosure 142, 144 can be selected so that the test subject can access the corners of the cage, but when the test subject is positioned directly below the attachment of the cable to the swivel 300, there is not enough slack in the cable to hang or extend downward from the back of the test subject and touch the floor of the cage. To maximize the available area for a given cage height, the cable can extend from directly above the center of the floor space of each enclosure. Thus, the height of the cage can be selected as a function of the major dimension of the cage floor (of a given enclosure) and the height of the test subject. For example, the height can be selected based on the following formula:

[0107] h ≥ (Rl 2 + R2 2 – 16a 2 ) / 16a

[0108] where h is the height of the cage, Rl is the length of the enclosure, R2 is the width of the enclosure, and a is the height of the animal.

[0109] Thus, the height can be a function of the major dimension Y of the cage floor according to the following formula:

[0110] h ≥ (Y 2 – 16a 2 ) / 16a.

[0111] A typical test subject mouse can have a height (a) of 20 mm. Thus, in some examples, the cage height h in millimeters can be a function of the major dimension Y (in millimeters) of the cage floor according to the following formula:

[0112] h ≥ (Y 2 – 6400) / 320 [mm].

[0113] More generally, the height of the cage can be selected as the major dimension of the cage floor (of each enclosure) multiplied by a factor. According to some aspects, the height of the cage can be 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, or at least, or 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.

[0114] In some example embodiments, the floor of the cage assembly can have a length of about 315 mm and a width of about 185 mm. Thus, where the floor length is divided by the partitions, each enclosure can have a floor with a long side of 185 mm and a short side of 157 mm. Thus, the floor area of each enclosure can have a major dimension of 242 cm (equal to the maximum diagonal between the corners of the enclosure). It is contemplated, therefore, that the height of the cage can have a minimum height of at least 163 mm, providing a height that is about 0.7 times the major dimension of the floor of the cage. According to various aspects, the floor area of each enclosure can 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 more than 400 mm. In some embodiments, the cage height can be about 260 mm. In further embodiments, the height of the cage can be at least 60 mm, at least 105 mm, at least 175 mm, at least 261 mm, or at least 480 mm.

[0115] It is contemplated that the above formula for selecting the height of the cage is not absolute, as the cable has some amount of stiffness (i.e., the cable has a limit to its flexibility), thereby limiting the ability of the cable to reach the floor of the cage. Thus, it is contemplated that the height of the cage can be less than the minimum height of the above formula, while still providing sufficient cage height to prevent the test subject from becoming entangled.

[0116] Optionally, the cage can include a feeder (e.g., a food tray or food dispenser). The feeder can optionally be coupled to the partitions 140 or other side walls, such that the feeder remains suspended.

[0117] Treatment assembly

[0118] Reference FIG. 8The treatment component 200 can be configured to provide a TTField to an organ tumor. The treatment component 200 may include a flexible circuit board 202 including a connector end 206 and one or more lead ends 208 at the ends of respective electrical leads 205 opposite to the connector end 206. The electrical leads 205 may be provided as part of a cable 204. Optionally, the flexible circuit board 202 may be configured to be coupled to a rotary joint 300. The cable 204 may be elongated and sufficiently flexible to allow a certain amount of twisting without requiring a rotary joint. The connector end 206 may optionally be a USB-C connector (e.g., a male USB-C connector). It is contemplated that using the flexible circuit board 202 as disclosed herein allows multiple electrical leads 205 to be provided as part of a unified structure, thereby avoiding cable or wire tangling and minimizing the space occupied by the electrical leads. Therefore, in some aspects, the cable 204 may be defined by a portion of the flexible circuit board 202.

[0119] In such FIG. 8 In the pre-use configuration shown, the lead ends 208 may be spaced apart along the longitudinal dimension 201 of the treatment assembly 200. 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 each, wherein these two rows extend along 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 the lead ends may be used. The cable 204 may extend perpendicularly or substantially perpendicularly to the longitudinal dimension 201.

[0120] Each lead end 208 may be configured to engage or be coupled to a respective plate 210. Thus, the treatment assembly 200 may include a plurality of electrodes, each electrode including a lead end 208 that contacts or is otherwise coupled to a respective plate 210. In some optional 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 serves as a control heating device), it is contemplated that at least one (optionally, each) plate may be a glass plate. In a further aspect, other types of electrodes are contemplated, such as, for example, electrodes formed of metal or other conductive materials.

[0121] The treatment assembly 200 can include an inner layer 212 having an outer surface 214 and an inner surface 216. The inner layer 212 can include a biocompatible, air-permeable adhesive such as, for example, polyurethane. In some embodiments, the inner layer can include a VANCIVE MED 9598A polyurethane film with an acrylic adhesive. The inner layer 212 can define a plurality of openings 218 through the inner layer for receiving a respective plate 210. The openings 218 can be spaced apart along the inner layer in a longitudinal direction. Although depicted as receiving independent plates, it is contemplated that each opening can optionally receive a plurality of plates (e.g., two plates) therein.

[0122] The plates 210 can have an upper surface 220 and a lower surface 222. The upper surface can be disposed against the electrical leads 208. A hydrogel layer 224 can be disposed against the lower surface 222 of each of the plates 210. The hydrogel layer 224 can optionally cover at least two adjacent plates 210. Optionally, the hydrogel layer 224 can cover the lower surface 222 of the plates 210 and an adjoining portion of the inner surface of the inner layer 212. In some optional aspects, the hydrogel layer 224 can be approximately 0.6 mm thick. The hydrogel 224 can include, for example, AG625 Sensing Gel manufactured by AXELGAARD.

[0123] A cover layer 230 can be attached to the outer surface 214 of the inner layer 212. The cover layer 230 can cover the plurality of electrical leads 208 of the flexible circuit board 202. The cover layer 230 can include one or more tab portions that extend beyond the perimeter of the inner layer 212. For example, the cover layer 230 can include two opposing tab portions 232 that complement one another when the cover layer defines a circumferential loop (e.g., when wrapped around the torso of a test subject, as further disclosed herein). Optionally, the tab portions 232 can be approximately one-half the width of the cover layer at their intersection with the main portion of the cover layer. When the cover layer is wrapped around the torso of a test subject, the tab portions 232 can extend past one another to attach to respective portions of the cover layer on opposite ends of the cover layer from the respective tab portions.

[0124] According to some optional aspects, the cover layer can have an inner surface that includes a biocompatible, non-woven adhesive. The non-woven adhesive can optionally be elastic along the longitudinal dimension 201. In some embodiments, the cover layer can include a medical non-woven adhesive tape manufactured by 3M under product number 1776.

[0125] Release layer 250 may contact and cover the underside of the biocompatible, breathable polyurethane adhesive on the inner surface 216 of inner layer 212, and the underside of hydrogel layer 224. The release layer may protect the adhesive before the therapeutic component is attached to the test subject. Release layer 250 may have a shape complementary to that of cover layer 230. Release layer may include separate tabs 252 configured to cover tab portions 232 of cover layer 230.

[0126] The treatment component may include at least one temperature sensor 260 (not shown, but the temperature sensor 260 may have a corresponding...) FIG. 10B and FIG. 11B The at least one temperature sensor (the location of temperature sensors 414 and 414') may be, for example, a thermistor or thermocouple. The at least one temperature sensor may optionally be part of the flexible circuit board 202. The at least one temperature sensor may include multiple temperature sensors. For example, temperature sensors may be positioned on the flexible circuit board 202, near each lead end 208. The multiple temperature sensors 260 may provide feedback to prevent the treatment assembly from overheating or causing burns to the test subject. For example, based on a temperature reading from temperature sensor 260 exceeding a threshold (e.g., 40°C), the TTField generator 18 may adjust or stop the sensing of the TTField at one or more electrodes. Additionally, the system 10 may receive feedback from temperature sensor 260 to maintain a consistent temperature in the control heater treatment assembly further disclosed herein. Optionally, the temperature sensors may be positioned within respective holes in their respective plates to measure the temperature between the plate and the hydrogel. In a further aspect, the temperature sensors may be positioned on the side of the respective plate opposite the hydrogel, thereby avoiding the need to form holes in the plate (and potentially making the plate undesirably fragile). In a further embodiment, the temperature sensor may be positioned on one side of the respective plate at a portion of the hydrogel (e.g., within three millimeters of the plate edge). For example, as... FIG. 10A As shown, pairs of plates 412 can share a single hydrogel layer 410, and each temperature sensor can be positioned between its respective pair of plates.

[0127] The portion of the treatment component that supports the test subject (e.g., excluding the weight of the cables) may optionally weigh less than about 10 percent of the test subject's body weight. For example, for a typical mouse, the portion of the treatment component that supports the test subject may weigh less than about 2.5 grams.

[0128] The treatment component can be flexible enough to conform to a portion of the torso of the test subject 12. Optionally, in such a way... FIG. 8In the pre-use configuration shown, the treatment component has a length along longitudinal dimension 201 sufficient to extend around the torso circumference of the test subject (both when positioned on the animal and during use). Optionally, the treatment component may be pre-formed into a three-dimensional shape configured to complement the torso shape of the test subject 12.

[0129] Optionally, the kit may include multiple treatment components 200, which have different lengths along the longitudinal dimension 201 (in pre-use configuration). In this way, the test subject can be fitted with treatment components of appropriate size (depending on the animal's girth / circumference). For example, the appropriately sized treatment components may be tightly wrapped around the test subject's torso girth. Optionally, additional covering material (which may be, for example, the same material as the outer layer) may be provided to reinforce attachment to the test subject and seal the edges of the adhesive material against dirt and debris that might hinder good contact.

[0130] refer to FIG. 9 The treatment component 200' can be configured for treating subcutaneous tumors. The treatment component 200' can have a configuration generally similar to that of the treatment component 200, having an inner layer 212' defining an opening 218' in which a receiving plate 210' is received. Optionally, it is contemplated that a hydrogel 224' can be received within the opening 218'. The flexible circuit board 202' may include cables 204' configured to connect to a rotary joint 300. FIG. 1 The connector end 206' and one or more lead ends 208' at the lead end opposite to the connector end 206'. The lead ends 208' can be configured to be coupled to their respective plates 210'. The outer layer 230' can be attached to the respective upper surfaces of the inner layer and the lead ends. The release layer 250', including separate tabs 252', can be attached to the bottom side of the inner layer 212' and the hydrogel 224'. The outer layer 230' and the release layer 250' can be constructed similarly to the outer layer 230 and the release layer 250.

[0131] The inner layer 212', the circuit board 202', and the cover layer 230' can cooperate to define a through-hole 270' that extends through the thickness of the treatment assembly 200' (except for the inner release layer, when present) and is configured to receive a subcutaneous tumor. Optionally, the through-hole 270' can have a diameter of between 10 mm and 15 mm. Optionally, the through-hole 270' can have a maximum diameter of about 15 mm. A cap 272' defines a receptacle 274' therein configured to receive an outwardly extending portion of a subcutaneous tumor, the cap can extend across the through-hole 270'. The cap 272' can be attached to the cover layer 230'. For example, the cap 272' can define a radially extending outer peripheral rim 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 (e.g., sawdust floor covering) from entering the hole and prevent contact between the treatment assembly and the subject.

[0132] In exemplary aspects, the opening 218' in which the plate 210' is received can have a predetermined relationship relative to the through-hole 270'. Optionally, in these aspects, and as shown in FIG. 27, the opening 218' can be coaxially aligned with the through-hole 270'. In these aspects, the plate 210' can be coaxially aligned with the through-hole 270' and the subcutaneous tumor when the tumor extends through the through-hole 270'. FIG. 9 and FIG. 11A In exemplary aspects, the opening 218' in which the plate 210' is received can have a predetermined relationship relative to the through-hole 270'. Optionally, in these aspects, and as shown in FIG. 27, the opening 218' can be coaxially aligned with the through-hole 270'. In these aspects, the plate 210' can be coaxially aligned with the through-hole 270' and the subcutaneous tumor when the tumor extends through the through-hole 270'.

[0133] According to some aspects, a kit can include a plurality of treatment assemblies 200' having through-holes 270' of different diameters and corresponding differently sized caps 272'. The plurality of treatment assemblies 200' having through-holes of different diameters can optionally have correspondingly different spacing between the lead end 208' and the plate 210'. In this manner, the subject 12 can be fitted with a treatment assembly 200' that is appropriately sized for its subcutaneous tumor. Optionally, the kit can further include a plurality of caps (optionally, identically sized and / or having different sizes) so that these caps can be replaced during a treatment procedure.

[0134] The length of the cable 204, 204' can be selected based on the enclosure dimensions such that the test subject 12 is not wrapped or entangled with the cable. An amount of slack can be attached to the back of the test subject in order to reduce the amount of free length of the cable. Thus, the cable can have an operational portion that is not attached to the test subject, where the operational portion can define an operational length of the cable. According to some aspects, the operational length of the cable can be selected such that when the test subject is positioned directly below the swivel joint, the cable does not have sufficient length to hang from the back of the test subject and touch the floor. Thus, it can be appreciated that the maximum operational length of the cable can be approximated as the height of the cage (or the height at which the cable is attached to the swivel joint) plus twice the height of the test subject. In further aspects, the cable length can be selected such that the cable does not have sufficient slack to hang from the back of the test subject to within a threshold distance t FIG. 6 ) from the floor of the cage. Thus, the maximum operational length of the cable can be approximated as the height from the floor at which the cable is attached to the swivel joint plus twice the height of the test subject, minus twice the threshold distance. Optionally, the threshold distance can be 0 mm, 1 mm, 2 mm, 4 mm, 6 mm, 10 mm, or more. In some aspects, the threshold distance can range from about 1 mm to about 10 mm, or from about 2 mm to about 6 mm. It is further contemplated that due to the limited flexibility of the cable, the length of the operational portion of the cable can be slightly greater than twice the height of the test subject plus the height of the cable, while the cable is unable to reach the floor of the cage.

[0135] To construct the treatment assembly 200, each of the plurality of plates 210 can be positioned within an opening in the inner layer of the treatment assembly. For example, in some embodiments, a pair of plates can be positioned within each opening. Alternatively, a single plate can be positioned within each opening. Each of the plurality of guide ends can be positioned in contact with a respective plate of the plurality of plates. As previously stated, the lead ends form respective electrodes when coupled with the plates disclosed herein. A cover layer can be attached to an outer surface of the inner layer such that the cover layer covers the plurality of electrodes. A hydrogel layer can be applied to a lower surface of each of the plurality of plates. In some aspects, a pair of plates positioned within a common opening in the inner layer can also share a hydrogel layer. Optionally, a hydrogel can be applied on adjoining portions of the inner surface of the inner layer.

[0136] Referring to FIG. 24-29 In further aspects, it is contemplated that the treatment assembly 200" can be configured to be positioned at least partially on the head of a test subject. For example, the head covering portion 9a of the treatment assembly 200" can be coupled to at least a portion of a mouse head, as FIG. 26The head covering portion 9a of the treatment assembly 200" can include a head wearable layer 6 configured to extend over a portion of the subject's head and couple to the subject with adhesive positioned on one or more interior surfaces of the head wearable layer 6. The treatment assembly 200" can further include a torso covering portion 9b configured to be placed on the subject's body (e.g., torso) (e.g., wrapped around the subject's body / torso, as further disclosed herein). The torso covering portion 9b of the treatment assembly 200" can include an inner adhesive wearable layer 1 configured to engage the subject's body (optionally, skin). The flexible circuit board 5 can include a plurality of lead ends. One end 8 of the flexible circuit board can be in communication with the TTField generator 18 (e.g., via a cable). The inner adhesive patch 4 can be coupled to the skin engaging side of the adhesive portion 6 with a portion of the flexible circuit board 5 positioned therebetween. The outer wearable layer 7 can be coupled at the outer side of the torso covering portion 9b of the treatment assembly. FIG. 1 The inner adhesive wearable layer 1 of the torso covering portion 9b can define at least one opening (optionally, a plurality of openings) that receives a corresponding portion of the water gel 2.

[0137] The ceramic plate 3 can be coupled to the lead ends of the flexible circuit board. The hydrogel 2 can be positioned below the ceramic plate 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, a plurality of openings) that receives a corresponding portion of the water gel 2.

[0138] The flexible circuit board 5 can include a plurality of lead terminals (and thus a plurality of electrodes 602) configured to be positioned on the head of the test subject, and one or more lead terminals (e.g., two lead terminals) (and thus a plurality of electrodes 604) configured to be positioned on the body (e.g., torso) of the test subject. In exemplary aspects, the plurality of lead terminals (for positioning on the head) are configured to be located under the head wearable layer 6, and the one or more lead terminals (for positioning on the torso) are configured to be located under the outer wearable layer 7 of the torso covering portion 9b, with each lead terminal covering over a respective ceramic plate 3 and hydrogel portion 2. Optionally, the plurality of lead terminals configured to be positioned on the head of the test subject can include a first set of lead terminals (e.g., three lead terminals corresponding to electrodes 602a) configured to be positioned on a first side of the head of the test subject (relative to a midline 606 bisecting the test subject into left and right sides), and a second set of lead terminals (e.g., three lead terminals corresponding to electrodes 602b) configured to be positioned on a second, opposite side of the head of the test subject (relative to the midline). The one or more lead terminals configured to be positioned on the body (e.g., torso) of the test subject can include a first lead terminal (corresponding to electrodes 604a) positioned on a first side of the body of the test subject relative to the midline, and a second lead terminal (corresponding to electrodes 604b) positioned on a second side of the body of the test subject relative to the midline. With reference to FIG. 28 , it is contemplated that the first lead terminal positioned on the first side of the body can cooperate with the second set of lead terminals on the second side of the head of the test subject to provide a TTField, and the second lead terminal positioned on the second side of the body (torso) can cooperate with the first set of lead terminals on the first side of the head of the test subject to provide a TTField. The TTFields can be provided in an alternating fashion to provide or facilitate a cross-over of TTFields.

[0139] In exemplary aspects, the flexible circuit board 5 can include a wave-shaped (e.g., meandering), serpentine, undulating, or zig-zag portion (generally referred to as an "alternating profile portion" 700) configured to facilitate flexibility to allow the test subject to move their neck. In use, it is contemplated that the alternating profile of this portion of the flexible circuit board 5 can provide a reduced starting length (to avoid unnecessary slack in the cable), while also allowing to straighten to increase the length and accommodate movement of the test subject (e.g., neck extension, twisting, and turning). In these aspects, and as shown in FIGS. 7A and 7B, the alternating profile portion can be positioned between the head covering portion 9a and the torso covering portion 9b. Further contemplated is that the alternating profile portion of the flexible circuit board 5 can be positioned between the plurality of lead terminals (for positioning on the head) and the at least one lead terminal (for positioning on the torso). FIG. 24-25 and FIG. 27-29 In exemplary aspects, the flexible circuit board 5 can include a wave-shaped (e.g., meandering), serpentine, undulating, or zig-zag portion (generally referred to as an "alternating profile portion" 700) configured to facilitate flexibility to allow the test subject to move their neck. In use, it is contemplated that the alternating profile of this portion of the flexible circuit board 5 can provide a reduced starting length (to avoid unnecessary slack in the cable), while also allowing to straighten to increase the length and accommodate movement of the test subject (e.g., neck extension, twisting, and turning). In these aspects, and as shown in FIGS. 7A and 7B, the alternating profile portion can be positioned between the head covering portion 9a and the torso covering portion 9b. Further contemplated is that the alternating profile portion of the flexible circuit board 5 can be positioned between the plurality of lead terminals (for positioning on the head) and the at least one lead terminal (for positioning on the torso).

[0140] Exemplary, non-limiting dimensions of the therapeutic assembly 200" are provided in millimeters in FIG. 29

[0141] It is contemplated that the material and properties of the inner adhesive wearable layer 1 of the torso covering portion 9b can be the same or similar to the material and properties of the covering layer 212, 212' disclosed herein with respect to the therapeutic assembly 200, 200'. Similarly, it is contemplated that the material and properties of the hydrogel 2 of the therapeutic assembly 200" can be the same or similar to the material and properties of the hydrogel 224, 224' disclosed herein with respect to the therapeutic assembly 200, 200'. It is further contemplated that the material and properties of the plate 3 of the therapeutic assembly 200" can be the same or similar to the material and properties of the plate 210, 210' disclosed herein with respect to the therapeutic assembly 200, 200'. It is further contemplated that the material and properties of the flexible circuit board 5 can be the same or similar to the material and properties of the flexible circuit board 202, 202' disclosed herein with respect to the therapeutic assembly 200, 200'. It is still further contemplated that the material and properties of the head wearable layer 6 and the outer wearable layer 7 of the therapeutic assembly 200" can be the same or similar to the material and properties of the covering / outer layer 230, 230' disclosed herein with respect to the therapeutic assembly 200, 200'.

[0142] With reference to FIG. 10A-11B The control heater therapeutic assembly 400 can be coupled to a control test subject and can be configured to mimic many or all or substantially all aspects of the therapeutic assembly 200. Likewise, the control heater therapeutic assembly 400' can be configured to mimic all or substantially all aspects of the therapeutic assembly 200' and can have a similar configuration and operation as described for the control heater therapeutic assembly 400. Similarly, the control heater therapeutic assembly can be configured to mimic all or substantially all aspects of the therapeutic assembly 200" and can have a similar configuration and operation as described for the control heater therapeutic assembly 400. For example, the control heater therapeutic assembly 400 can be configured to generate heat to maintain a similar temperature against the skin of the control test subject, thereby limiting differences between aspects of the control and test groups. As another example, the control heater therapeutic assembly 400 can be configured to have substantially or approximately the same weight as a therapeutic test subject assembly capable of generating a TTField, as disclosed further herein.

[0143] ​The control heater assembly 400 can include a flexible circuit board 402. The flexible circuit board 402 can include a cable 404 and a connector end 406 configured to couple to the swivel 300. The flexible circuit board can include a plurality of resistive heaters positioned in locations corresponding to where electrodes are positioned in the treatment assembly 200. For example, the flexible circuit board 402 can include eight zones 410 (e.g., two rows of four zones 410) in which electrodes would be in the corresponding treatment assembly. More generally, the flexible circuit board 402 can have any desired number of zones, each corresponding to a location of an electrode in a corresponding treatment assembly. Optionally, each zone 410 can include two resistive heaters 412 (shown schematically in FIG. 11 as individual units separate from the circuit board 402 and in detail as components of the circuit board 402 in FIG. 11). A temperature sensor 414 can be disposed in each zone 410, optionally in the center of each zone 410, and equally spaced between the heaters 412. The heaters 412 can optionally include glass plates. FIG. 10A

[0144] Optionally, the control heater assembly 400 can include an inner layer 420 defining a plurality of through-holes through which the heaters 412 can be positioned. Optionally, the control heater assembly 400 can include a cover layer 430 extending across the upper side of the flexible circuit board. A release liner 440 can releasably attach the lower surface of the inner layer. The inner layer 420 and the cover layer 430 can include the same material and the same geometry as the corresponding treatment assembly so as to feel similar to the test subject. Optionally, a hydrogel layer 416 can cover the lower side of the flexible circuit board 402. Likewise, the control heater assembly 400' can have a structure corresponding to the structure of the treatment assembly 200', with 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 are further contemplated that mimic the shape, weight, heat, and in other ways, the perceived experience of the treatment assembly 200".

[0145] The control heater assembly 400 can be coupled to the TTField generator 18 via the swivel 300. The swivel 300 can control the output of the resistive heaters 412 based on feedback from the temperature sensors 260. In some embodiments, the control heater assembly 400 can maintain a set temperature (e.g., 38.5 or 39 degrees Celsius) to mimic the temperature reached by the corresponding treatment assembly 200, 200', 200" as a byproduct of providing the TTField. In further embodiments, the control heater assembly 400 can be selectively controlled to maintain a temperature matching the temperature of the treatment assembly on the corresponding test subject receiving TTField treatment. ​

[0146] The control heater assembly 400, 400' can further have a weight similar to the weight of the respective therapeutic assembly 200, 200', 200". Thus, the control heater assembly can produce the same perceived experience in the test subject. In this way, the effect of the TTField on tumor development can be isolated from other aspects of the test procedure.

[0147] In exemplary aspects, kits can be provided that have both a control heater assembly 400, 400' and a therapeutic assembly 200, 200', 200". In these aspects, it is contemplated that each therapeutic assembly provided in the kit can have a corresponding control heater assembly positioned within the same kit, thereby maximizing consistency among the control group and the experimental / therapeutic group.

[0148] It is contemplated that the embodiments disclosed herein can be used to provide other currents, fields, and heat to different body parts of the test subject in addition to providing TTFields.

[0149] In some optional aspects, a wide therapeutic assembly (and corresponding control heater assembly) for a test subject having a wide torso can have a length of about 200 mm to about 250 mm (relative to the longitudinal axis 201), a width of about 100 mm to about 130 mm (optionally, 110 mm to 115 mm), and a thickness of about 1.6 mm to about 1.7 mm. In some optional aspects, a narrow therapeutic assembly (and corresponding control heater assembly) for a test subject having a narrow torso can have a length of about 200 mm to about 250 mm, a width of about 80 mm to about 115 mm (optionally, 100 mm to 110 mm), and a thickness of about 1.6 mm to about 1.7 mm. In further optional aspects, a therapeutic assembly (and corresponding control heater assembly) for a subcutaneous tumor can 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.

[0150] Collar

[0151] It is contemplated that the test subject can be inclined to chew or bite on the therapeutic assembly 200, 200', 200" or the control heater therapeutic assembly 400, 400'. With reference to FIG. 30-32To discourage such behavior, it is contemplated that the collar 500 can be ring-shaped. Optionally, the collar 500 can have two opposing ends that are coupled together to form a ring shape. For example, the collar 500 can include a protrusion 502 positioned at a first end 506 that is configured to be received into one or more holes 504 in an opposing second end 508. The protrusion 502 can have an enlarged distal end that is larger in diameter than the one or more holes 504 such that once inserted into the hole, it cannot inadvertently fall out (due to the engagement between these surfaces of the protrusion and the portion of the second end that defines the hole). It is contemplated that the one or more holes 504 can include a plurality of holes 504 spaced around the circumference of the collar 500 such that the collar can have a selectable operational diameter depending on which hole the protrusion 502 is inserted into in order to adapt the collar to differently sized test subjects.

[0152] Optionally, the collar 500 can have an inner surface 510 that is jagged, serrated, or toothed. Optionally, the collar 500 can have an outer surface 512 that is axially tapered. The collar 500 can be oriented such that the outer surface tapers in a direction away from the head of the test subject.

[0153] It is contemplated that both the over-weighting and the sound reflection of the collar can shorten the life of the test subject. Accordingly, in some aspects, the collar 500 can define a plurality of holes 514 that can optionally extend axially through the collar (through the thickness of the collar). The holes 514 can reduce the amount of material, and thus the weight of the collar, as well as minimize sound reflections that can cause stress to the test subject.

[0154] The collar 500 can optionally be flexible. Optionally, the collar can include a polymer such as, for example, silicone. Swivel joint assembly FIG. 15

[0155] Referring to FIG. 12 and FIG. 1 The rotary union 300 can be mounted to a cap 120 within a rotary union housing 180. The rotary union housing 180 can include a sidewall 182 that is integral to the cap 120. The rotary union housing 180 can receive a removable inner circumferential insert 184. The rotary union housing can further include a top cover 186 coupled to the sidewall 182.

[0156] The rotary joint 300 can include a damping plate 302 that is attached to a top cover 186 via screws or other fasteners. The top cover 186 can be part of a rotary joint module. The damping plate 302 can be coupled to a motor mounting plate 304 via screws 306. The rotary joint 300 can have a central axis 308, and a motor 310 can rotate about the central axis 308. The motor 310 can be coupled to the motor mounting plate 306 via screws 312. A rotatable base 314 can be attached to the motor 310 via screws 316. Thus, the rotatable base can be rotatable relative to the motor mounting plate 304 via the motor. A bearing housing 316 can be coupled to the rotatable base 314 via a standoff 318. The rotatable base 314 can define a depending tab 320 that can be coupled to a flexible circuit assembly 322.

[0157] In some optional aspects, the top cover 186 can include at least one input device (e.g., a button) configured to start and stop treatment (e.g., TTFields or heat). Optionally, the at least one input device can include a plurality of input devices, where each input device is configured to control operation of a different component of the system. In some aspects, respective input devices can be configured to control TTField application and heat application. In further aspects, an input device can be configured to start and stop operation of the rotary joint. In further aspects, the top cover 186 can include a display configured to display information, such as, for example, experiment identification information (e.g., cage number, electrode type) or mode of operation (e.g., idle, treatment, heating, pause). In various aspects, the top cover 186 can provide a communication port that can communicate with the rotary joint 300 to provide communication between the signal generator 12 FIG. 13 ) and the treatment / control heater assembly.

[0158] Also referring to FIG. 15 and FIG. 18A , the flexible circuit assembly 322 can include a printed circuit board (PCB) 324 with an input / output connector 326 attached. The connector 326 can provide communication to an upper portion of the rotary joint. The printed circuit board 324 can define a patterned portion 328 extending between a base portion 330 and a cable connector end 332. The patterned portion 328 can have a structure that enables the printed circuit board 324 to twist so that the connector end 332 can pivot relative to the base portion 330, as further described herein. In exemplary aspects, the patterned portion 328 can have a serpentine, undulating, zig-zag, or wave pattern. A pair of sensor connector portions 334 can extend from the base portion 330.

[0159] Also referring to FIG. 18B , FIG. 19 andFIG. 15 The bearing housing 316 can house a bearing 340 (e.g., a ball bearing or a nylon bearing) that can receive and support a pivot body 342 within an inner race thereof. The pivot body 342 can define a slot 344 therein that can receive the connector end 332 of the printed circuit board 324. The slot 344 can receive and engage the connector end 332 such that when the connector end is pivoted about the central axis 308, the pivot body can correspondingly pivot. (Although the figures show the connector end 332 remaining in place as the pivot body pivots, it should be understood that in use, the connector end pivots with the pivot body.) The pivot body 342 can define a cantilevered tab 346 that extends parallel to the central axis 308.

[0160] A centering spring 348 can extend from a standoff 350 attached to the bearing housing 316 to engage the protrusion 352 or other radially extending surface that is spaced apart from or extends away from the central axis 308 of the swivel joint 300. The centering spring 348 can bias the pivot body 316 into a neutral position 354. In use, when the printed circuit board 324 is not subject to or is substantially not subject to a torque, then the pivot body can be in the neutral position 354.

[0161] Referring to FIG. 18A , FIG. 18B , FIG. 19 and FIG. 23 , a pair of sensors 356 (e.g., electro-optical sensors such as, for example, VISHAY TCPT1600X01 sensors) can be attached to the bearing housing 316 via respective sensor mounts 358. The sensors 356 can be in communication with the PCB 324 at the sensor connector portion 334. The sensors 356 can be in communication with a processor (e.g., a PLC controller on the circuit board 359, as shown in FIG. 8 The sensors can have a light source, a photodetector, and a light path between the light source and the photodetector. The sensors 356 can be positioned such that when the pivot body 316 is in the neutral position, the cantilevered tab 346 can block both of the sensors 356. As a test subject walks within the cage, it can twist the cable 204 (see FIG. 19 ) thereby applying a twist to the pivot body 342 and causing the pivot body to pivot from its neutral position. As the pivot body pivots from the neutral position 350 in a first direction 360 (see FIG. 23When pivoted sufficiently, the cantilevered tab 346 can be positioned outside the light path of the first sensor 356A, and the first sensor can detect light from the light source in the photodetector. In this manner, the rotary joint 300 can detect twisting of the cable in the first direction. The processor can cause the motor 310 to rotate in the first direction 360 to relieve the twist on the cable. Optionally, the rotary joint can be configured to remain stationary until a minimum threshold angle from the neutral position 350 is reached, so as to prevent excessive movement that can wear out the motor. Optionally, the motor can rotate a minimum angular distance so as to minimize an excessive number of small movements. Likewise, when the pivoting body is pivoted sufficiently in the second direction 362 (opposite the first direction) from the neutral position 350, the second optical sensor 356B can detect this and the processor can cause the motor to rotate in the second direction to relieve the twist on the cable. In this manner, the rotary joint can limit the amount of twist in the cable 204, thereby allowing the subject to move freely within the cage.

[0162] A limiter 364 can be attached to each sensor mount 358. Each limiter 364 can include a central extension that can act as a stop to prevent the pivoting body from pivoting more than a threshold angle from the neutral position 350, thereby preventing the printed circuit board 324 from breaking.

[0163] The pivoting body 342 can 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 can include a USB-C connector (e.g., a female USB-C connector) that is complementary to the connector end of the flexible circuit board. Optionally, the connector 380 can include a CAN bus connection.

[0164] The rotary joint can include a slip ring that can maintain electrical communication through the rotary joint, thereby enabling communication between the therapy assembly 200 (or therapy assembly 200' or therapy assembly 200''), the heater assembly 400 (or heater assembly 400' ), and the TTField generator 18. The slip ring can enable communication of at least twenty communication channels.

[0165] The computing device 1001 can be in communication with the rotary joint 300 (e.g., through the cable 20 or another cable) to track and / or record various metrics. In further aspects, the computing device 1001 can be embodied as the PCB 359 (e.g., the processor 360) FIG. 1controller. For example, the metrics can include some or all of the following metrics: number of rotations, number of rotations in a first selected duration of time, frequency of motor movement, frequency of motor movement in a second selected duration of time, number of motor movements including a change in direction, number of motor movements including a change in direction in a third selected duration of time, duration of constant movement, and a log of motor movements and corresponding times of motor movements. Such metrics can indicate abnormal behavior in the test subject. Further, such metrics can indicate that the rotary joint 300 is malfunctioning. In some aspects, a warning (e.g., a warning light or a sound alarm) can be activated to notify a user that the rotary joint 300 is malfunctioning or that the test subject is behaving abnormally. In further aspects, the computing device or controller in communication with the rotary joint can be configured to receive user input. The user input can define one or more thresholds, such as, for example, a frequency threshold (e.g., a frequency of change in rotational direction) or a time threshold (e.g., a duration of constant rotation threshold). Upon exceeding the respective threshold, a warning can be activated.

[0166] In further aspects, the computing device can generate and output a log report including at least one of the collected metrics. The log report can further output a metric comparison based on a comparison of the metric to an average metric. The average metric can be an average metric for similar test subjects or an average metric for a given test subject over a selected time period (e.g., over the course of an hour, a day, or a week). For example, the average metric can include an average amount of movement per day for the test subject. It is thus contemplated that a decrease in the amount of movement per day can indicate a worsening health condition of the test subject. It is further contemplated that an amount of movement that is too high or an amount of movement that is too low compared to other similar test subjects can indicate a relative health condition of the test subject. It is further contemplated that monitoring various metrics can allow for identification of modifications to ensure that the animal test subject survives until the end of the experimental period.

[0167] Reference is made to FIG. 20The experimental subjects 12 of the experimental group 14 can be fitted with respective treatment assemblies. The treatment assemblies can be selected to treat a particular tumor (e.g., treatment assembly 200 for organ tumors or treatment assembly 200' for subcutaneous tumors). The treatment assemblies can be appropriately sized. For example, for organ tumors, the longitudinal length of the treatment assembly can be appropriate to wrap snugly around the torso girth of the subject along the torso at the given tumor. For subcutaneous tumors, the through-hole and cap of the treatment assembly can be selected to fit the subcutaneous tumor with minimal excess space. The cable length of the treatment assembly can be selected to enable the subject to freely traverse the floor area of the enclosure, while not providing excess length that can become entangled, as disclosed herein. The release liners can be removed to allow the adhesive to engage the skin of the subject. The fur of the subject can be removed at the application area with a trimming device and / or depilatory cream (e.g., VEET depilatory cream). Similarly, the subjects 12 of the control group can be fitted with respective control heater treatment assemblies 400 or control heater treatment assemblies 400' (to match the counterparts of the experimental group).

[0168] The treatment assembly can be positioned on the body such that the electrodes are positioned as close to the tumor as possible. In various aspects, the treatment assembly (or control heater assembly) can be positioned on the body of the subject so as to minimize or eliminate interruption of natural movement. For example, if the treatment assembly can be positioned away from the hind legs or forelegs of the mouse to allow for natural movement. The treatment assembly can be selected based at least in part on the size of the mouse. For example, a narrow treatment assembly can be positioned on a mouse weighing less than 23 grams, and a wide treatment assembly can be positioned on a mouse weighing more than 23 grams.

[0169] The treatment array (or control heater assembly) can be oriented such that the cable extends toward the tail / rear end of the subject. It is contemplated that the subcutaneous treatment assembly and control heater assembly can have formed bends (e.g., 90 degree bends) that can enable the cable to extend into the middle of the back of the subject, and then extend along the back toward the rear end. The formed bends can be provided in either direction, depending on the side of the subject on which the subcutaneous tumor is positioned. Adhesive (e.g., plasters) can be provided on the subject to facilitate adhesion of the treatment assembly (or control heater assembly).

[0170] The subjects can be placed within respective enclosures of the cage assembly. The connector end of each treatment assembly and control heater treatment assembly 400 can be attached to a respective swivel joint.

[0171] The treatment assemblies can be controlled to provide TTFields to the subjects. For example, with reference to FIG. 21 and FIG. 20TTFields from 50-500 kHz (optionally, 150-500 kHz) can be delivered to an organ tumor 22 ( FIG. 21 ) or a subcutaneous tumor 22' ( Computing device ). Optionally, the TTFields can be delivered sequentially along separate propagation axes (to provide alternating fields). For example, a first pair of opposing electrodes can apply a first electric field across the tumor along a first propagation axis 60. A second pair of electrodes positioned with a second propagation axis 62 that is perpendicular or substantially perpendicular to the first propagation axis can alternate with the first pair of opposing electrodes to provide alternating fields across the tumor. For the treatment assembly 200, each electrode can cooperate with respective electrodes positioned furthest from its location (e.g., on the other side of the subject's body) to provide alternating TTFields. Optionally, each electrode can be independently controlled to provide customized treatment. The control heater treatment assembly can be controlled via the TTField generator or other controller to provide an ineffective control agent heat to match or substantially match the temperature of the treatment assembly. Treatment can optionally last for about 1-2 weeks.

[0172] Tumors of the experimental and control groups can be compared during and after treatment. For example, for subcutaneous tumors, the cap can be removed to expose the tumor while leaving the treatment assembly attached to the subject, and the tumor size can be measured with calipers. Organ tumors can be measured via, for example, magnetic resonance imaging (MRI), ultrasound (US), or computed tomography (CT) scans. The treatment assembly can be removed prior to such scans.

[0173] FIG. 22

[0174] Exemplary aspects A system 1000 is shown, including an exemplary configuration of a computing device 1001 for use in system 10.

[0175] Computing device 1001 can include one or more processors 1003, system memory 1012, and a bus 1013 that couples various components of computing device 1001, including the one or more processors 1003, to system memory 1012. In the case of multiple processors 1003, computing device 1001 can utilize parallel computing.

[0176] Bus 1013 can include one or more of several 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.

[0177] The computing device 1001 can operate as and / or include various computer- readable media (e.g., non-transitory). Computer-readable media can be any available media that is accessible by the computing device 1001 and includes both volatile and nonvolatile media, removable and non-removable media. The system memory 1012 has the 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 memory 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 TTField provisioning software 1006, which are accessible / in operable by the one or more processors 1003.

[0178] The computing device 1001 can also include other removable / non-removable, volatile / nonvolatile computer storage media. The mass storage device 1004 can provide nonvolatile 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, magnetic cassettes or other magnetic storage devices, flash memory cards, CD-ROM, digital versatile disks (DVD) or other optical storage, random access memories (RAM), read only memories (ROM), electrically erasable programmable read only memories (EEPROM), etc.

[0179] Any number of program modules can be stored on the mass storage device 1004. The operating system 1005 and TTField provisioning software 1006 can be stored on the mass storage device 1004. One or more of the operating system 1005 and TTField provisioning software 1006 (or some combination thereof) can include the program modules and TTField provisioning software 1006. Temperature data 1007 can also be stored on the mass storage device 1004. The temperature data 1007 can be stored in any one of one or more databases known in the art. The databases can be centrally located or distributed throughout the network 1015.

[0180] A user can enter commands and information into the computing device 1001 through input devices (not shown). Such input devices include, but are not limited to, a keyboard, pointing devices (e.g., a computer mouse, remote control), a microphone, a joystick, a scanner, tactile input devices (such as gloves and other body coverings), motion sensors, etc. These and other input devices are connected to the one or more processors 1003 through the user interface 1002 that is coupled to the bus 1013, but can 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 universal serial bus (USB), and / or a network adapter 1008.

[0181] A display device 1011 can also be connected to the bus 1013 via an interface, such as a display adapter 1009. It is contemplated that the computing device 1001 might have more than one display adapter 1009, and the computing device 1001 might have more than one display device 1011. The display device 1011 can be a monitor, an LCD (Liquid Crystal Display), a LED (Light Emitting Diode) display, a television, a smart mirror, smart glass, and / or a projector. In addition to the display device 1011, other output peripheral devices can include components that can be connected to the computing device 1001 using the input / output interface 1010, such as speakers (not shown) and a printer (not shown). Any steps and / or results of any methods described herein can be output (or made to be output) to an output device. Such output can be any form of visual representation including, but not limited to, text, graphics, animation, audio, tactile, etc. The display 1011 and the computing device 1001 can be part of one device, or separate devices.

[0182] 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 a personal computer, a computing station (e.g., a work station), a portable computer (e.g., a laptop, a mobile phone, a tablet device), a smart device (e.g., a smart phone, a smart watch, an activity tracker, smart clothing, smart accessories), a security and / or surveillance device, a server, a router, a network computer, a peer device, an edge device, or other common network node, etc. 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 a network connection can be through a network adapter 1008. The network adapter 1008 can implement both wired and wireless environments. Such networking environments are commonplace in residences, offices, enterprise-wide computer networks, intranets, and the Internet. It is contemplated that the remote computing devices 1014a, 1014b, 1014c can optionally have some or all of the components of the computing device 1001 disclosed as part thereof.

[0183] Application programs and other executable program components, such as an operating system 1005, are shown herein as discrete blocks, although it is understood that such programs and components can reside at various times in different storage components of the computing device 1001, and are executed by one or more processors 1003 of the computing device 1001. Embodiments of the electrode data processing software 1006 can be stored in or transmitted across some form of computer readable media. Any of the disclosed methods can be performed by a processor executing instructions embodied in computer readable media.

[0184] ​

[0185] In view of the described products, systems, and methods, and variations thereof, certain more particularly described aspects of the application are described below. These particularly recited aspects should not, however, be construed as having any limiting effect on any differing claims comprising different or more general teachings herein, or as having any limiting effect on the “particular” aspects other than in some respect slightly narrower than the inherent meaning of the language in which they are written.

[0186] Aspect 1A: A cage assembly comprising: at least one enclosure, each enclosure having: a floor defining a floor area having a major dimension; a lid having a bottom surface, wherein a spacing between the bottom surface of the lid and the floor defines a cage height; and at least one sidewall extending between the floor and the lid, wherein a ratio of the cage height to the major dimension of the floor area for each of the at least one enclosure is at least 0.70.

[0187] Aspect 2A: The cage assembly of Aspect 1A, wherein the at least one enclosure comprises a first enclosure and a second enclosure.

[0188] Aspect 3A: The cage assembly of Aspect 1A, wherein the at least one enclosure consists of a first enclosure and a second enclosure.

[0189] Aspect 4A: The cage assembly of Aspect 2A or Aspect 3A, wherein the first enclosure and the second enclosure share a common sidewall separating the floor area of the first enclosure from the floor area of the second enclosure.

[0190] Aspect 5A: The cage assembly of Aspect 4A, wherein the common sidewall defines at least one opening between the first enclosure and the second enclosure.

[0191] Aspect 6A: The cage assembly of Aspect 5A, wherein each of the first enclosure and the second enclosure includes a respective shade subassembly extending inwardly within the enclosure from the common sidewall, and wherein the shade subassembly at least partially encloses the opening within the common sidewall.

[0192] Aspect 7A: The cage assembly of any of the preceding Aspects, wherein the floor of each enclosure defines a corner, each corner of the floor of the enclosure having a radius of at least 17 mm.

[0193] Aspect 8A: The cage assembly of any of the preceding Aspects, wherein the major dimension of the floor area of each enclosure is no greater than 250 mm.

[0194] Aspect 9A: The cage assembly of any of Aspects 2A-8A, wherein the floors of the first enclosure and the second enclosure are integrally configured.

[0195] Aspect 10A: The cage assembly of any of Aspects 2A-9A, wherein the lids of the first enclosure and the second enclosure are integrally configured as a lid assembly.

[0196] Aspect 11A: The cage assembly of Aspect 10A, wherein the cover assembly includes first and second openings that provide communication with the first and second enclosure portions, respectively, wherein the first opening is configured to provide communication for a first cable, and wherein the second opening is configured to provide communication for a second cable.

[0197] Aspect 12A: The cage assembly of Aspect 11A, wherein the cover assembly includes first and second rotary joint assemblies positioned in covering relation with the first and second openings, respectively, wherein the first rotary joint assembly is configured to receive a proximal portion of the first cable, and wherein the second rotary joint assembly is configured to receive a proximal portion of the second cable.

[0198] Aspect 13A: The cage assembly of Aspect 12A, wherein each of the first and second rotary joint assemblies includes a motor housing and a motor received within the motor housing, wherein the motor of the first rotary joint assembly is configured to be coupled to a first cable to allow adjustment of the first cable, and wherein the motor of the second rotary joint assembly is configured to be coupled to a second cable to allow adjustment of the second cable.

[0199] Aspect 14A: The cage assembly of Aspect 1A, wherein the at least one enclosure portion includes a first enclosure portion, wherein the cover includes a rotary joint assembly positioned in covering relation with the first enclosure portion, wherein the cover further includes an opening that provides communication with the first enclosure portion, wherein the opening is configured to provide communication between the cable and the rotary joint assembly.

[0200] Aspect 15A: The cage assembly of Aspect 14A, wherein the rotary joint assembly includes a motor, wherein the motor is configured to be coupled to a proximal portion of the cable to allow adjustment of movement of the cable.

[0201] Aspect 16A: The cage assembly of any of Aspects 4A-13A, wherein the at least one sidewall of each of the first and second enclosure portions further includes: a front sidewall; a rear sidewall; and a lateral sidewall opposite the common sidewall and extending between the front and rear sidewalls.

[0202] Aspect 17A: The cage assembly of Aspect 16A, wherein at least a portion of the front sidewall of the first and second enclosure portions is integrally configured.

[0203] Aspect 18A: The cage assembly of Aspect 16A or Aspect 17A, wherein the rear sidewall of the first enclosure portion and the second enclosure portion are integrally configured.

[0204] Aspect 19A: The cage assembly of Aspect 17A, wherein the front sidewall of the first enclosure portion and the second enclosure portion comprises: a base portion secured to the lateral sidewalls of the first enclosure portion and the second enclosure portion; a door pivotably coupled to the base portion, wherein the door is configured for movement about and between: a closed position in which the door cooperates with the front sidewall, lateral sidewalls, and rear sidewall of the first enclosure portion and the second enclosure portion and the cover to enclose an interior space within the cage assembly; and an open position in which the interior space of the cage assembly is accessible.

[0205] Aspect 20A: The cage assembly of Aspect 19A, wherein the door is pivotably coupled to the base portion by a hinge connection.

[0206] Aspect 21A: The cage assembly of Aspect 19A or Aspect 20A, further comprising a latch mechanically coupled to the door, wherein the latch is movable about and between: a latched position that prevents pivotal movement of the door when the door is in the closed position; and an unlocked position that allows pivotal movement of the door relative to the base portion.

[0207] Aspect 22A: The cage assembly of any of the preceding aspects, wherein the floor, the cover, and the at least one sidewall of each enclosure portion comprises polycarbonate.

[0208] Aspect 23A: The cage assembly of any of the preceding aspects, wherein at least a portion of the cover and the at least one sidewall of each enclosure portion is transparent.

[0209] Aspect 24A: The cage assembly of any of the preceding aspects, wherein the cover defines an opening configured to receive an electrical cord.

[0210] Aspect 25A: The cage assembly of any of the preceding aspects, wherein the floor of each enclosure portion comprises bedding.

[0211] Aspect 26A: The cage assembly of any of the preceding aspects, wherein at least one sidewall of each enclosure portion comprises a ventilation opening.

[0212] Aspect 27A: The cage assembly of Aspect 26A, further comprising at least one filter configured to cover the at least one ventilation opening of the at least one sidewall.

[0213] Aspect 28A: The cage assembly of Aspect 27A, further comprising a frame configured to mechanically couple the filter to the at least one sidewall.

[0214] Aspect 29A: The cage assembly of Aspect 27A, wherein the cage assembly is sealed such that all or substantially all ventilation to each enclosure travels through the at least one filter before entering a ventilation opening.

[0215] Aspect 30A: The cage assembly of any of the preceding aspects, wherein the sidewalls of each enclosure have equal lengths.

[0216] Aspect 31A: The cage assembly of any of the preceding aspects, wherein a ratio of the cage height of each of the at least one enclosure to a major dimension of the floor area is at least 1.0.

[0217] Aspect 32A: A cage assembly comprising: at least one enclosure, each enclosure having: a floor defining a floor area having a major dimension; a lid having a bottom surface, wherein a spacing between the bottom surface of the lid and the floor defines a cage height; and at least one sidewall extending between the floor and the lid, wherein the height h is a function of the major dimension Y of the floor according to the following formula: h ≥ (Y2 - 6400) / 320, where h and Y are in millimeters.

[0218] Aspect 33A: A method comprising: placing an animal test subject within each enclosure of a cage assembly according to any of the preceding aspects; and coupling a distal end of a cable to the animal test subject within each enclosure, wherein at least 90% of a floor area of the enclosure is accessible by the animal test subject.

[0219] Aspect 34A: The method of claim 33, further comprising: coupling a proximal end of each cable to a swivel assembly, wherein each cable has an operational portion having an operational length, wherein each operational length is selected such that each test subject can not be in a position within the respective enclosure in which a spacing between the operational portions of the cables is within a threshold distance of the floor.

[0220] Aspect 35A: The method of Aspect 33A or Aspect 34A, wherein the animal test subject is a mouse.

[0221] Aspect 36A: The method of Aspect 35A, wherein the cage assembly includes a first enclosure and a second enclosure, wherein a first mouse is placed within the first enclosure, and wherein a second mouse is placed within the second enclosure.

[0222] Aspect 37A: The method of Aspect 36A, wherein the first enclosure and the second enclosure share a common sidewall that separates the floor region of the first enclosure from the floor region of the second enclosure, wherein the common sidewall defines at least one opening between the first enclosure and the second enclosure, and wherein the at least one opening allows for communication between the first mouse and the second mouse.

[0223] Aspect 38A: The method of any one of Aspects 33A-37A, wherein the electrical wire is coupled to the animal test subject through a therapy assembly that includes an array of transducers.

[0224] Aspect 39A: The method of Aspect 38A, further comprising: using the electrical wire and the therapy assembly to apply an electric field to the animal test subject within at least one enclosure.

[0225] Aspect 40A: The method of Aspect 39A, wherein the animal test subject has a tumor, and wherein the electric field is a tumor treatment field.

[0226] Aspect 41A: The method of any one of Aspects 33A-40A, further comprising: inspecting or accessing the animal test subject through the cage assembly without removing the animal test subject from the cage assembly.

[0227] Aspect 42A: The method of any one of Aspects 33A-41A, further comprising: removing the animal test subject from the cage assembly; and autoclaving the floor, the lid, and the at least one sidewall of each enclosure.

[0228] Aspect IB: A therapy assembly comprising: an inner layer having an inner surface and an outer surface, wherein the inner layer defines a plurality of openings extending therethrough; a plurality of plates, each plate at least partially received within a respective one of the plurality of openings of the inner layer; therapy circuitry comprising: a cable comprising a plurality of electrical leads having a plurality of electrical lead ends, each electrical lead electrically connected to a respective one of the plurality of electrical lead ends; and a cover attached to the 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.

[0229] Aspect 2B: The treatment assembly of Aspect IB, wherein at least one of the plurality of plates comprises a ceramic plate.

[0230] Aspect 3B: The treatment assembly of Aspect IB, wherein at least one of the plurality of plates comprises a glass plate.

[0231] Aspect 4B: The treatment assembly of any one of Aspects IB-3B, wherein at least one of the plurality of electrodes is configured to generate an electric field through a corresponding one of the plurality of plates.

[0232] Aspect 5B: The treatment assembly of any one of Aspects IB-4B, wherein the plurality of electrodes of the treatment circuitry have respective top surfaces, and wherein the cover layer extends across the top surfaces of the electrodes of the cable.

[0233] Aspect 6B: The treatment assembly of any one of Aspects IB-5B, wherein each of the plurality of plates has a lower surface and an opposing upper surface, wherein the treatment assembly further comprises a hydrogel layer on the lower surface of each of the plurality of plates.

[0234] Aspect 7B: The treatment assembly of any one of Aspects IB-6B, wherein the treatment circuitry further comprises at least one temperature sensor.

[0235] Aspect 8B: The treatment assembly of any one of Aspects IB-7B, wherein the inner layer and the cover layer cooperate to define a bore through the treatment assembly, wherein the bore is configured to receive a subcutaneous tumor through the bore.

[0236] Aspect 9B: The treatment assembly of Aspect 8B, further comprising a cap extending across the bore and defining a receptacle therein configured to receive the subcutaneous tumor, wherein the cap is attached to the cover layer.

[0237] Aspect 10B: The treatment assembly of Aspect 8B or Aspect 9B, wherein the plurality of plates are positioned radially outward of the bore defined through the treatment assembly.

[0238] Aspect 11B: The treatment assembly of Aspect 9B or Aspect 10B, wherein the cap comprises an outer peripheral rim, and wherein the treatment assembly further comprises an adhesive ring covering the outer peripheral rim and securing the cap to the cover layer.

[0239] Aspect 12B: The treatment assembly of any one of Aspects 1B-11B, wherein the treatment assembly has a longitudinal dimension in a pre-use configuration, wherein the cover layer comprises a biocompatible nonwoven adhesive, wherein the nonwoven adhesive is elastic along the longitudinal dimension.

[0240] Aspect 13B: The treatment assembly of Aspect 12B, wherein, in a use configuration, the cable extends perpendicularly or substantially perpendicularly relative to the longitudinal dimension.

[0241] Aspect 14B: The treatment assembly of any one of Aspects 1B-13B, wherein the inner layer comprises a biocompatible air-permeable polyurethane adhesive on an inner surface of the inner layer.

[0242] Aspect 15B: The treatment assembly of Aspect 14B, wherein the cover layer has an inner surface comprising a biocompatible nonwoven adhesive.

[0243] Aspect 16B: The treatment assembly of any one of Aspects 1B-15B, wherein the plurality of electrodes comprises a plurality of electric field generating electrodes, wherein the plurality of electric field generating electrodes are configured to transmit an electric field through a corresponding one of the plurality of panels.

[0244] Aspect 17B: The treatment assembly of Aspect 16B, wherein the therapy circuitry further comprises a plurality of thermistors.

[0245] Aspect 18B: The treatment assembly of Aspect 17B, wherein each of the plurality of electrodes and each of the plurality of thermistors is in communication with each of the plurality of panels.

[0246] Aspect 19B: The treatment assembly of any one of Aspects 1B-18B, wherein the treatment assembly weighs less than 2.5 grams.

[0247] Aspect 20B: The treatment assembly of any one of Aspects 1B-19B, wherein the treatment assembly is flexible enough to conform circumferentially to a portion of a torso of the animal test subject.

[0248] Aspect 21B: The treatment assembly of any one of Aspects 1B-20B, wherein the cable comprises an end connector positioned on an end of the cable opposite the plurality of electrodes, wherein the end connector is configured to allow the cable to be connected to an electrical signal generator.

[0249] Aspect 22B: The treatment assembly of Aspect 14B, further comprising a release layer contacting the biocompatible air-permeable polyurethane adhesive on the inner surface of the inner layer.

[0250] Aspect 23B: The treatment assembly of Aspect 22B, wherein the release layer has a shape that is complementary to a shape of the cover layer.

[0251] Aspect 24B: The treatment assembly of any one of Aspects 1B-23B, wherein the cover layer defines at least one tab portion that extends beyond the inner layer.

[0252] Aspect 25B: The treatment assembly of Aspect 2B, wherein the at least one tab portion comprises two opposing tab portions that are complementary to each other when the cover layer defines a circumferential ring.

[0253] Aspect 26B: The treatment assembly of any one of Aspects 1B-7B or Aspects 12B-25B, wherein the plurality of openings comprises a plurality of longitudinally spaced apart openings.

[0254] Aspect 27B: The treatment assembly of any one of Aspects 1B-26B, wherein the treatment circuitry and the cable are integrally configured as a flexible printed circuit board.

[0255] Aspect 28B: A method of manufacturing the treatment assembly of any one of Aspects 1B-27B, the method comprising: positioning the plurality of plates within respective openings in the inner layer of the treatment assembly; positioning each of the plurality of electrodes of the treatment circuitry in contact with one of the plurality of plates; and attaching the cover layer to an outer surface of the inner layer, wherein the cover layer covers the plurality of electrodes of the treatment circuitry.

[0256] Aspect 29B: The method of Aspect 28B, further comprising applying a hydrogel layer to a lower surface of each of the plurality of plates.

[0257] Aspect 30B: The method of Aspect 29B, wherein the lower surfaces of at least two of the plurality of plates share a hydrogel layer.

[0258] Aspect 31B: A method comprising: electrically coupling at least a portion of the electrodes of the treatment assembly of any one of Aspects 1B-27B to an electrical signal generator; attaching the treatment assembly to an animal test subject having a tumor, wherein the plates of the treatment assembly enclose at least a portion of the tumor; and using the electrical signal generator to generate an electrical signal; and using the at least a portion of the electrodes of the treatment assembly to generate an electric field that passes through a respective one of the plurality of plates from the electrical signal.

[0259] Aspect 32B: The method of Aspect 31B, wherein the tumor is an organ tumor, wherein, in the pre-use configuration, the plurality of openings and the plurality of plates are longitudinally spaced along a longitudinal axis of the treatment assembly, and wherein, in the use configuration, the plurality of openings and the plurality of plates are circumferentially spaced about a torso of the animal test subject to enclose the organ tumor.

[0260] Aspect 33B: The method of Aspect 31B, wherein the tumor is a subcutaneous tumor, wherein the plurality of openings are radially spaced with apertures extending through the treatment assembly, and wherein the apertures receive at least a portion of the subcutaneous tumor.

[0261] Aspect 34B: The method of Aspect 33B, further comprising positioning a cap over the subcutaneous tumor and securing the cap to the cover layer of the treatment assembly.

[0262] Aspect 35B: The method of any one of Aspects 31B-34B, wherein generating the electrical signal using the electrical signal generator comprises sequentially generating a first electrical signal and a second electrical signal, and wherein generating the electric field from the electrical signal using the at least a portion of the electrodes of the treatment assembly comprises generating a first electric field across the tumor using a first electrode and a second electrode from the first electrical signal and generating a second electric field across the tumor using a third electrode and a fourth electrode from the second electrical signal.

[0263] Aspect 36B: The method of Aspect 35B, wherein the first electric field and the second electric field have respective propagation axes, and wherein the propagation axis of the first electric field intersects the propagation axis of the second electric field.

[0264] Aspect 37B: The method of any one of Aspects 28B-36B, wherein generating the electric field using the electrical signal generator comprises generating the electric field at a frequency between 50 and 500 kHz.

[0265] Aspect 38B: The method of any one of aspects 31B-37B, wherein the animal test subject is a member of an experimental group, and wherein the method further comprises: electrically coupling at least a portion of the electrodes of a control heating device according to any one of aspects 39B-42B to an electrical signal generator; attaching the control heating device to a second animal test subject having a tumor, wherein the second animal test subject is a member of a control group, wherein the heater of the second treatment assembly encloses at least a portion of the tumor; and using the electrical signal generator to generate heat by the heater of the control heating device, wherein the at least a portion of the electrodes of the second treatment assembly deliver heat through a corresponding one of the plurality of plates, and wherein the heat generated by the control heating device mimics heat generated by the first treatment assembly during delivery of the electric field.

[0266] Aspect 39B: A control heating device comprising: circuitry comprising: a plurality of zones positioned in a spaced configuration that matches a configuration of the plurality of electrodes of a treatment assembly as recited in any one of aspects IB-27B, at least one heater positioned 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 circuitry.

[0267] Aspect 40B: The control heating device of aspect 39B, wherein the at least one temperature sensor comprises a plurality of temperature sensors, wherein each of the plurality of temperature sensors is positioned at each of the plurality of zones.

[0268] Aspect 41B: The control heating device of aspect 39B or aspect 40B, wherein the circuitry and the cable are integrally configured as a flexible printed circuit board.

[0269] Aspect 42B: The control heating device of any one of aspects 39B-41B, further comprising: an inner layer having an upper surface and comprising a plurality of openings, wherein each of the zones is disposed within one of the plurality of openings; and a cover layer extending across the upper surface of the inner layer.

[0270] Aspect 43B: The treatment assembly of any one of aspects IB-27B, wherein the plurality of electrodes comprises: a plurality of head electrodes configured to be positioned on a head of a test subject; and a plurality of torso electrodes configured to be positioned on a torso of the test subject.

[0271] Aspect 44B: The therapy assembly of aspect 43B, wherein the therapy circuitry comprises a serpentine portion extending from the plurality of torso electrodes to the plurality of head electrodes.

[0272] Aspect 45B: The therapy assembly of aspect 43B or aspect 44B, wherein the plurality of head electrodes comprises a first set of electrodes positioned on a first side relative to a mid-sagittal plane and a second plurality of electrodes positioned on a second side opposite the first side relative to the mid-sagittal plane, wherein the plurality of torso electrodes comprises at least a first torso electrode positioned on the first side and at least a second torso electrode positioned on the second side.

[0273] Aspect 1C: A rotary joint assembly having a longitudinal axis and comprising: an upper portion; a lower portion rotatably coupled to the upper portion, wherein the lower portion has a connector configured to securely engage a cable, wherein the lower portion is configured to remain in electrical communication with the upper portion when the lower portion is rotated relative to the upper portion; a motor disposed between the upper portion and the lower portion 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 upon receiving a signal from the sensor indicative of a threshold twist in the cable, the controller is configured to cause the motor to rotate in a direction corresponding to a direction of the twist in the cable.

[0274] Aspect 2C: The rotary joint assembly of aspect 1C, wherein the connector of the lower portion is an electrical connector, wherein the electrical connector is configured to securely engage an electrical cable.

[0275] Aspect 3C: The rotary joint assembly of aspect 2C, wherein the electrical connector is configured for electrical communication with an electrical signal generator, and wherein the electrical connector is further configured to allow electrical communication between the electrical signal generator and the electrical cable.

[0276] Aspect 4C: The rotary joint assembly of any of aspects 1C-3C, wherein the controller is configured to cause the motor to rotate in a direction corresponding to a direction of the twist in the cable until the controller receives a signal from the sensor indicative that the twist in the cable has dropped below a second threshold.

[0277] Aspect 5C: The rotary joint assembly of any of aspects 1C-4C, further comprising a mounting assembly attached to the upper portion of the rotary joint relative to the longitudinal axis, wherein the lower portion of the rotary joint is rotatably coupled to the mounting assembly via the upper portion of the rotary joint.

[0278] Aspect 6C: The rotary union assembly of Aspect 5C, wherein the mounting assembly is configured to be secured to a top surface of the cage.

[0279] Aspect 7C: The rotary union assembly of Aspect 5C or Aspect 6C, wherein the mounting assembly defines an opening in communication with the cable outlet.

[0280] Aspect 8C: The rotary union assembly of any one of Aspects 1C-7C, wherein the lower portion includes a bottom plate positioned below the motor and engaged with the motor, and wherein the motor imparts rotational force to the lower portion through the bottom plate.

[0281] Aspect 9C: The rotary union assembly of any one of Aspects 1C-8C, wherein the upper portion includes a support plate covering the motor.

[0282] Aspect 10C: The rotary union assembly of any one of Aspects 1C-9C, wherein the upper portion further includes a dampening plate covering the motor.

[0283] Aspect 11C: The rotary union assembly of any one of Aspects 1C-10C, wherein the controller is configured to detect abnormal rotation of the rotary union assembly, wherein the abnormal rotation is detected by at least one of: (1) one or more signals from the sensor indicative of a change in frequency of rotational direction exceeding a frequency threshold; or (2) one or more signals from the sensor indicative of continuous rotation in a single direction exceeding a time threshold.

[0284] Aspect 12C: The rotary union assembly of Aspect 11C, wherein the controller is configured to receive user input to define at least one of the frequency threshold or the time threshold.

[0285] Aspect 13C: The rotary union assembly of Aspect 11C or Aspect 12C, further comprising a warning indicator, wherein the controller is configured to activate the warning indicator upon detection of abnormal rotation.

[0286] Aspect 14C: The rotary union assembly of Aspect 13C, wherein the warning indicator includes at least one of a visible indicator or an audible indicator.

[0287] Aspect 15C: The rotary joint assembly of any one of aspects 1C-14C, wherein the sensor is a torque sensor comprising: a pivot body pivotably coupled to the lower portion of the rotary joint about a pivot axis and configured to be coupled to the cable such that a twist of the cable applies a torque to the pivot body causing a pivot of the pivot body relative to the lower portion of the rotary joint, wherein the pivot body comprises a radially extending surface extending radially outward relative to the pivot axis; a spring configured to bias the pivot body relative to the lower portion of the rotary joint to a neutral position; first and second electro-optical sensors radially spaced from the pivot axis of the pivot body and in respective angular positions relative to the pivot body, wherein upon the pivot body being pivoted a first threshold angular distance in a first direction from the neutral position, the radially extending surface of the pivot body is configured to effect a state change in the first electro-optical sensor, and wherein upon the pivot body being pivoted a second threshold angular distance in a second, opposite direction from the neutral position, the radially extending surface of the pivot body is configured to effect a state change in the second electro-optical sensor.

[0288] Aspect 16C: The rotary joint assembly of aspect 15C, further comprising a printed circuit board having a first portion rotationally fixed to the lower portion of the rotary joint, a second portion pivotable with the pivot body, and at least one cutout such that the printed circuit board comprises a patterned portion enabling the first portion to pivot relative to the second portion.

[0289] Aspect 17C: The rotary joint assembly of aspect 15C or aspect 16C, wherein each of the first and second electro-optical sensors comprises a light source, a photodetector, and a light path between the light source and the photodetector, wherein the radially extending surface of the pivot body is configured to block the respective light path of each of the first and second electro-optical sensors when the pivot body is in the neutral position, wherein the state change in the first electro-optical sensor upon the pivot body being pivoted the first threshold angular distance in the first direction from the neutral position comprises the first electro-optical sensor no longer detecting that the radially extending surface blocks the light path of the first electro-optical sensor.

[0290] Aspect 18C: The rotary joint assembly of aspect 17C, wherein the radially extending surface of the pivot body comprises a protrusion.

[0291] Aspect 19C: The rotary joint assembly of any one of aspects 1C-18C, wherein the motor is a brushless gimbal-mounted motor.

[0292] Aspect 20C: The rotary joint assembly of any one of Aspects 1C-19C, further comprising the cable, wherein the cable has a proximal end portion secured to the connector and an opposite distal end, wherein the cable is configured to move in response to a force applied to the distal end portion of the cable.

[0293] Aspect 21C: The rotary joint assembly of any one of Aspects 1C-20C, further comprising a slip ring configured to provide electrical communication between the upper portion and the lower portion as the lower portion rotates relative to the upper portion.

[0294] Aspect 22C: The rotary joint assembly of any one of Aspects 1C-21C, wherein the cable is part of a flexible printed circuit board.

[0295] Aspect 23C: A method comprising: securing a proximal end portion of a cable to a connector of the rotary joint assembly of any one of Aspects 1C-22C; and using the controller to cause the motor to rotate in a direction corresponding to a first direction of a twist in the cable in response to the twist in the cable in the first direction.

[0296] Aspect 24C: The method of Aspect 23C, wherein the cable is an electrical cable, and wherein the cable has a distal end portion electrically coupled to an electrode array.

[0297] Aspect 25C: The method of Aspect 24C, wherein the electrode array is coupled to an animal test subject.

[0298] Aspect 26C: The method of Aspect 25C, wherein the animal test subject is placed within a cage, and wherein the rotary joint assembly is secured to the cage.

[0299] Aspect 27C: The method of any one of Aspects 23C-26C, further comprising: using the controller to determine an abnormal rotation based on at least one of: (1) one or more signals from the sensor indicative of a change in frequency of rotation direction exceeding a frequency threshold; or (2) one or more signals from the sensor indicative of continuous rotation in a single direction exceeding a time threshold.

[0300] Aspect 28C: A system comprising: the rotary joint assembly of any of Aspects 1C-22C; a computing device comprising a memory in communication with at least one processor, wherein the memory comprises instructions that, when executed, cause the at least one processor to perform a method comprising: storing in the memory at least one metric selected from the group consisting of: number of rotations, number of rotations over a first selected duration of time, frequency of motor movement, frequency of motor movement over a second selected duration of time, number of motor movements including a change in direction, number of motor movements including a change in direction over a second selected duration of time, duration of constant movement, and a log of motor movements and corresponding times of motor movements.

[0301] Aspect 29C: The rotary joint assembly of Aspect 28C, wherein the memory comprises instructions that, when executed, cause the at least one processor to perform the method further comprising: generating a log report, wherein the log report comprises the at least one metric.

[0302] Aspect 30C: The rotary joint assembly of Aspect 29C, wherein the log report further comprises at least one comparison of the at least one metric and an average of the at least one metric over a specified time.

[0303] Aspect 1D: A system comprising: the cage assembly of any of Aspects 1A-32A; and the rotary joint assembly of any of Aspects 1C-22C.

[0304] Aspect 2D: The system of Aspect 1D, further comprising the treatment assembly of any of Aspects 1B-27B.

[0305] Aspect 3D: The system of Aspect 1D, further comprising the counter heating device of any of Aspects 39B-42B.

[0306] Aspect 4D: A method of using the system of any of Aspects 1D-3D.

[0307] While the foregoing application has been described in some detail for purposes of clarity and understanding, certain changes and modifications will be apparent to those skilled in the art. Therefore, the foregoing application is not to be taken as limiting in scope, but is intended to be accorded the full scope consistent with the claims.

Claims

1. A therapeutic component comprising: An inner layer having an inner surface and an outer surface, wherein the inner layer defines a plurality of openings extending therethrough; Multiple plates, each plate being received at least partially within a corresponding opening of the multiple openings in the inner layer; The treatment circuit system includes: Cables with multiple leads; and Multiple leads, each electrical lead being electrically connected to a corresponding lead of the plurality of leads; and A cover layer is attached to the outer surface of the inner layer and covers multiple lead ends of the cable. The plurality of lead ends contact a corresponding plate in the plurality of plates to define a plurality of electrodes, each of the plurality of electrodes including a corresponding lead end and a corresponding plate; The plurality of electrodes includes a plurality of head electrodes configured to be located on the head of the test subject and a plurality of torso electrodes configured to be located on the torso of the test subject; and The treatment circuit system includes a serpentine section extending from the plurality of torso electrodes to the plurality of head electrodes.

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

3. 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 of the plurality of electrodes is configured to generate an electric field through a corresponding plate of the plurality of plates.

5. The treatment assembly of claim 1, wherein the plurality of electrodes of the treatment circuit system have respective top surfaces, and wherein the cover layer extends across the top surfaces of the electrodes of the cable.

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

7. The treatment component according to claim 1, wherein, The treatment circuit system also includes at least one temperature sensor.

8. The treatment component of claim 1, wherein the inner layer and the overlying layer cooperate to define a hole through the treatment component, wherein the hole is configured to receive a subcutaneous tumor through it.

9. The treatment assembly of claim 8, further comprising a cap extending across the orifice and defining a receiver therein, the receiver being configured to receive the subcutaneous tumor, wherein the cap is attached to the covering layer.

10. The treatment component according to claim 8, wherein, The plurality of plates are located radially outside the holes defined by the treatment assembly.

11. The treatment assembly of claim 9, wherein the cap includes an outer peripheral edge, and wherein the treatment assembly further includes an adhesive ring that covers the outer peripheral edge and secures the cap to the cover layer.

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

13. The treatment assembly of claim 12, wherein, in the usage configuration, the cable extends perpendicularly or substantially perpendicularly to the longitudinal dimension.

14. The treatment component according to any one of the preceding claims, wherein, The inner layer includes a biocompatible, breathable polyurethane adhesive on the inner surface of the inner layer.

15. The therapeutic assembly of claim 14, wherein the covering layer has an inner surface comprising a biocompatible nonwoven adhesive.

16. The therapeutic component according to any one of claims 1 to 13, wherein, The plurality of electrodes includes a plurality of electric field generating electrodes, wherein the plurality of electric field generating electrodes are configured to transmit an electric field through a corresponding plate of the plurality of plates.

17. The therapeutic component of claim 16, wherein, The treatment circuit system also includes multiple thermistors.

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

19. The treatment component of claim 1, wherein the weight of the treatment component is less than 2.5 grams.

20. The therapeutic component according to claim 1, wherein, The therapeutic component is flexible enough to conform circumferentially to a portion of the torso of the animal test subject.

21. The treatment component according to claim 1, wherein, The cable includes an end connector located at one end of the cable opposite to the plurality of electrodes, wherein the end connector is configured to allow the cable to be connected to an electrical signal generator.

22. The therapeutic assembly of claim 14, further comprising a release layer that contacts the biocompatible, breathable polyurethane adhesive on the inner surface of the inner layer.

23. The therapeutic assembly of claim 22, wherein the release layer has a shape complementary to the shape of the covering layer.

24. The therapeutic component according to claim 1, wherein, The cover layer defines at least one tab portion that extends beyond the inner layer.

25. The treatment component according to claim 2, wherein, The at least one tab portion includes two opposing tab portions that are complementary to each other when the cover layer defines a circumferential ring.

26. The therapeutic component according to claim 1, wherein, The plurality of openings includes a plurality of longitudinally spaced openings.

27. The therapeutic component according to claim 1, wherein, The treatment circuit system and the cables are integrally constructed as a flexible printed circuit board.

28. The treatment assembly of claim 1, wherein the plurality of head electrodes comprises a first set of electrodes positioned on a first side relative to the midline and a second plurality of electrodes positioned on a second side opposite to the first side relative to the midline, wherein the plurality of trunk electrodes comprises at least a first trunk electrode positioned on the first side and at least a second trunk electrode positioned on the second side.

29. A method of manufacturing a therapeutic component according to any one of claims 1-28, the method comprising: Position multiple plates within corresponding openings in the inner layer of the treatment assembly; Each of the multiple electrodes in the treatment circuit system is positioned to contact one of the multiple plates; as well as A cover layer is attached to the outer surface of the inner layer, wherein the cover layer covers the plurality of electrodes of the therapeutic circuit system.

30. The method of claim 29, further comprising applying a hydrogel layer to the lower surface of each of the plurality of plates.

31. The method of claim 30, wherein at least two of the plurality of plates share a hydrogel layer on their lower surfaces.

32. A system for providing a tumor treatment field, comprising: At least one therapeutic component according to any one of claims 1-28; as well as An electrical signal generator that communicates with the treatment component, wherein the electrical signal generator is configured to generate an electric field via the at least one treatment component.

33. The system according to claim 32, wherein, In the pre-use configuration, the plurality of openings and the plurality of plates are longitudinally spaced along the longitudinal axis of the treatment assembly, and in the use configuration, the plurality of openings and the plurality of plates are circumferentially spaced around the torso of the animal test subject to surround the organ tumor.

34. The system of claim 32, wherein the plurality of openings are radially spaced from the orifices extending through the treatment component, and wherein the orifices are configured to receive at least a portion of a subcutaneous tumor.

35. The system according to claim 34, wherein, The treatment component includes a cap configured to be positioned above the subcutaneous tumor and to be secured to the covering layer of the treatment component.

36. The system of claim 32, wherein the electrical signal generator is configured to sequentially generate a first electrical signal and a second electrical signal, wherein the first and second electrodes of the plurality of electrodes are configured to generate a first electric field across the tumor from the first electrical signal, and wherein the third and fourth electrodes of the plurality of electrodes are configured to generate a second electric field across the tumor from the second electrical signal.

37. The system of claim 36, wherein the first electric field and the second electric field have their own propagation axes, and wherein the propagation axis of the first electric field intersects the propagation axis of the second electric field.

38. The system according to claim 32, wherein, The electrical signal generator is configured to generate electrical signals at frequencies between 50 and 500 kHz.

39. The system of claim 32, further comprising at least one control heating device, said at least one control heating device comprising: The circuit system includes: Multiple regions, wherein the multiple regions are positioned at intervals that match the configuration of the multiple electrodes of the treatment component according to any one of claims 1-28; At least one heater located in each of the multiple zones; At least one temperature sensor; and A cable communicating with the at least one heater and the at least one temperature sensor of the circuit system.

40. The system of claim 39, wherein the at least one temperature sensor comprises a plurality of temperature sensors, wherein each of the plurality of temperature sensors is located in each of the plurality of regions.

41. The system according to claim 39, wherein, The circuitry and cables of the at least one control heating device are integrally constructed as a flexible printed circuit board.

42. The system of claim 39, wherein the at least one control heating device further comprises: An inner layer having an upper surface and including multiple openings, wherein each region in the region is disposed within one of the multiple openings; as well as A cover layer extending across the upper surface of the inner layer.

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