Cage assembly for animal test subjects
The cage assembly system with a swivel assembly addresses the challenges of cable entanglement and restricted movement in TTFields testing, ensuring reliable and consistent safety testing of TTFields in animal test subjects.
Patent Information
- Application Number
- JP2022537716
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Priority Date
- 2020-10-23
- Filing Date
- 2020-12-18
- Publication Date
- 2025-06-17
- Estimated Expiration
- 2040-12-18
AI Technical Summary
Current systems for testing tumor treating fields (TTFields) in animal test subjects face challenges such as animal biting or damaging electrical components, cable twisting, and restricted movement due to inadequate cable slack.
A cage assembly system with a swivel assembly that allows for flexible cable management, preventing cable entanglement and allowing the test subjects to move freely while maintaining electrical connectivity.
The system ensures reliable and consistent safety testing of TTFields by minimizing cable-related issues and allowing unrestricted movement of the test subjects, thereby reducing stress and improving data accuracy.
Smart Images

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Abstract
Description
Technical Field
[0001] Cross - reference to Related Applications This application claims the benefit and priority of the filing dates of U.S. Provisional Patent Application No. 62 / 951,599, filed on December 20, 2019, and U.S. Provisional Patent Application No. 63 / 104,788, filed on October 23, 2020, and the entireties of those patent applications are incorporated herein by reference.
[0002] 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 systems for use with animal test subjects (Hereinafter, also simply referred to as "animal subject" or "test subject") including.
Background Art
[0003] Tumor treating fields or TTFields are low - intensity (e.g., 1 - 3 V / cm) alternating electric fields within the intermediate frequency range (100 - 300 kHz). This non - invasive treatment targets solid tumors and is described in Patent Document 1, which is incorporated herein by reference in its entirety. TTFields disrupt cell division through physical interactions with key molecules during mitosis. TTField therapy is an approved monotherapy for recurrent glioblastoma and an approved combination therapy with chemotherapy for newly diagnosed patients. These electric fields are non - invasively induced by transducer arrays (i.e., arrays of electrodes) placed directly on the patient's scalp. TTFields also appear to be beneficial for treating tumors in other parts of the body. Laboratory studies have begun to test intermediate - frequency alternating electric fields (tumor treating fields or TTFields) on subcutaneous tumors and orthotopic tumors located on the torso of small animals (e.g., mice).
Prior Art Documents
Patent Documents
[0004]
Patent Document 1
Summary of the Invention
Means for Solving the Problems
[0005] Described herein in various aspects is a cage assembly for animal test subjects. Optionally, the cage assembly can be used to house one or more animal test subjects receiving TTFields or a control treatment.
[0006] The cage assembly can include at least one enclosure. Each enclosure can have a floor defining a floor area with a major dimension, and a cover having a bottom surface. The distance between the bottom surface of the cover and the floor can define the cage height. At least one sidewall can extend between the floor and the cover. The ratio of the cage height to the major dimension of the floor area of each enclosure of the at least one enclosure can be at least 0.70.
[0007] The at least one enclosure can include a first enclosure and a second enclosure.
[0008] The at least one enclosure can consist of a first enclosure and a second enclosure.
[0009] The first enclosure and the second enclosure can share a common sidewall that separates the floor area of the first enclosure from the floor area of the second enclosure.
[0010] The common sidewall can define at least one opening between the first enclosure and the second enclosure.
[0011] Each of the first enclosure and the second enclosure can include respective shelter sub-assemblies that extend inwardly from the common sidewall within the enclosure. The shelter sub-assemblies can at least partially surround the opening within the common sidewall.
[0012] The floor of each enclosure may define a corner, and each corner of the floor of the enclosure has a radius of at least 17 mm.
[0013] The major dimension of the floor area of each enclosure can be 250 mm or less.
[0014] The floor of the first enclosure and the floor of the second enclosure can be integrally constructed.
[0015] The cover of the first enclosure and the cover of the second enclosure can be integrally constructed as a cover assembly.
[0016] The cover assembly may include a first opening and a second opening that respectively provide communication with the first enclosure and the second enclosure. The first opening can be configured to provide communication to a first cable (Hereinafter, also referred to as "electrical cord") and the second opening can be configured to provide communication to a second cable. (Hereinafter, also referred to as "electrical cord")
[0017] The cover assembly may include a first swivel assembly and a second swivel assembly that are respectively disposed to cover the first opening and the second opening. The first swivel assembly can be configured to receive the proximal portion of the first cable, and the second swivel assembly can be configured to receive the proximal portion of the second cable.
[0018] Each of the first swivel assembly and the second swivel assembly may include a motor housing and a motor received within the motor housing. The motor of the first swivel assembly can be configured to be coupled to the first cable to allow adjustment of the first cable. The motor of the second swivel assembly can be configured to be coupled to the second cable to allow adjustment of the second cable.
[0019] At least one enclosure may include the first enclosure. The cover may include a swivel assembly disposed to cover the first enclosure. The cover may further include an opening that provides communication with the first enclosure. The opening can be configured to provide communication between the cable and the swivel assembly.
[0020] The swivel assembly may include a motor. The motor may be configured to be coupled to the proximal portion of the cable to allow adjustment of the movement of the cable.
[0021] At least one side wall of each of the first enclosure and the second enclosure may further include a front side wall, a rear side wall, and a transverse side wall that faces a common side wall and extends between the front side wall and the rear side wall.
[0022] At least a portion of the front side wall of the first enclosure and at least a portion of the front side wall of the second enclosure may be integrally constructed.
[0023] The rear side wall of the first enclosure and the rear side wall of the second enclosure may be integrally constructed.
[0024] The front side walls of the first enclosure and the second enclosure may include a base portion fixed to the transverse side walls of the first enclosure and the second enclosure, and a door pivotally coupled to the base portion. The door may be configured for movement between and around a closed position where the door cooperates with the front side walls, transverse side walls, rear side walls, and cover of the first enclosure and the second enclosure to enclose the internal space within the cage assembly, and an open position where the internal space of the cage assembly is accessible.
[0025] The door may be pivotally coupled to the base portion by a hinge connection.
[0026] The cage assembly may further include a latch mechanically coupled to the door. The latch may be movable between and around a latched position that prevents pivotal movement of the door when the door is in the closed position and an unlatched position that allows pivotal movement of the door relative to the base portion.
[0027] The floor, cover, and at least one side wall of each enclosure may include polycarbonate.
[0028] At least a portion of the cover and at least one side wall of each enclosure may be transparent.
[0029] The cover may define an opening configured to receive an electrical cord.
[0030] The floor of each enclosure may be provided with padding.
[0031] At least one side wall of each enclosure may be provided with a ventilation opening.
[0032] The cage assembly may further comprise at least one filter configured to cover at least one ventilation opening of at least one side wall.
[0033] The cage assembly may further comprise a frame configured to mechanically connect the filter to at least one side wall.
[0034] The cage assembly may be sealed such that all or substantially all ventilation to each enclosure proceeds through the at least one filter before entering the ventilation opening.
[0035] The side walls of each enclosure may have equal lengths.
[0036] The ratio of the cage height to the major dimension of the floor area of each enclosure of at least one enclosure may be at least 1.0.
[0037] The cage assembly may comprise at least one enclosure. Each enclosure may have a floor defining a floor area having a major dimension, and a cover having a bottom surface. The distance between the bottom surface of the cover and the floor may define the cage height. At least one side wall may extend between the floor and the cover. The height h can be a function of the major dimension Y of the floor according to the formula h≧(Y2 - 6400) / 320, where h and Y are in millimeters.
[0038] The method may include the steps of placing an animal subject in each enclosure of a cage assembly and connecting the distal end of a cable to the animal subject within each enclosure. At least 90% of the floor area of the enclosure may be accessible by the animal subject.
[0039] The method may further include the step of connecting the proximal end of each cable to a swivel assembly. Each cable may have an operating portion having an operating length. Each operating length may be selected such that each test subject cannot be at a position within each enclosure where the distance between the operating portions of the cables is within a threshold distance of the floor.
[0040] The animal subject may be a mouse.
[0041] The cage assembly may comprise a first enclosure and a second enclosure. A first mouse may be placed in the first enclosure. A second mouse may be placed in the second enclosure.
[0042] The first enclosure and the second enclosure may share a common sidewall that separates the floor area of the first enclosure from the floor area of the second enclosure. The common sidewall may define at least one opening between the first enclosure and the second enclosure. The at least one opening may permit communication between the first mouse and the second mouse.
[0043] The electrical cord may be connected to the animal subject through a treatment assembly comprising a transducer array.
[0044] The method may further include the step of using the electrical cord and the treatment assembly to apply an electric field to the animal subject within at least one enclosure.
[0045] The animal subject may have a tumor, and the electric field may be a tumor treatment electric field.
[0046] The method may further include inspecting or accessing the animal subject through the cage assembly without removing the animal subject from the cage assembly.
[0047] The method may further include removing the animal subject from the cage assembly and autoclaving the floor, cover, and at least one side wall of each enclosure.
[0048] Additional advantages of the present invention will be described in part in the following description, become apparent in part from the description, or may be learned by practice of the present invention. The advantages of the present invention are realized and achieved using the elements and combinations particularly pointed out in the appended claims. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention as claimed.
[0049] These and other features of the preferred embodiments of the present invention will become more apparent in the detailed description with reference to the accompanying drawings.
Brief Description of the Drawings
[0050]
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DETAILED DESCRIPTION OF THE INVENTION
[0051] Hereinafter, the present invention will be more fully described with reference to the accompanying drawings, which show some, but not all, embodiments of the invention. Indeed, the invention may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. These embodiments are provided so that this disclosure will satisfy applicable legal requirements. Like reference numerals refer to like elements throughout. It is understood that the invention is not limited to the specific methodologies and procedures described, as these may vary. It is also understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of the invention.
[0052] Many modifications and other embodiments of the invention described herein will come to mind to those skilled in the art to which this invention pertains having the benefit of the teachings presented in the foregoing description and the related drawings. Therefore, it is to be understood that the invention is not to be limited to the specific embodiments disclosed and that modifications and other embodiments are intended to be included within the scope of the appended claims. Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation.
[0053] As used herein, the singular forms "a", "an" and "the" include plural referents unless the context clearly dictates otherwise. For example, the use of the term "an electrode" can refer to one or more of such electrodes.
[0054] All technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs, unless otherwise clearly defined.
[0055] As used herein, the terms "optional" or "optionally" mean that the subsequently described event or circumstance may or may not occur, and that the description includes examples where the event or circumstance occurs and examples where it does not occur.
[0056] As used herein, the term "at least one of" is intended to be synonymous with "one or more of". For example, "at least one of A, B, and C" explicitly includes only A, only B, only C, and each combination.
[0057] Ranges may be expressed herein as from a particular "about" value and / or to another particular "about" value. When such a range is expressed, other aspects include from a particular value and / or to another particular value. Similarly, when a value is expressed as an approximation, it is understood that the use of the antecedent "about" forms other aspects with the particular value. It is further understood that each endpoint of a range is significant both in relation to the other endpoint and independently of the other endpoint. Optionally, in some aspects, when a value is approximated by use of the antecedent "about", values within up to 15%, up to 10%, up to 5%, or up to 1% (above or below) of the specifically recited value may be included within the scope of those aspects. Similarly, the use of "substantially" (e.g., "substantially parallel") or "generally" (e.g., "generally planar") should be understood to include embodiments where the angle is within about 10 degrees, within 5 degrees, or within 1 degree.
[0058] As used herein, the word "or" means any one of the specifically listed elements and also includes any combination of the listed elements.
[0059] Unless otherwise expressly stated, it is not intended that the methods described herein be construed as requiring that the steps of the method be performed in a particular order. Thus, unless a method claim actually recites the order in which the steps occur, or the order of the steps is otherwise expressly limited in the claim or the specification, no order is intended to be inferred in any respect. This preserves any possible non-expressive basis for interpretation, including questions of theory regarding the sequence of steps or the flow of operations, plain meaning derived from grammatical construction or punctuation, and the number or types of aspects described in the specification.
[0060] In the following description and claims, when the words "comprising" or "including" are used, the words "comprising" or "including" can optionally be replaced with the words "consisting essentially of" or "consisting of" to form other embodiments.
[0061] The following description provides specific details for a thorough understanding. Nevertheless, those skilled in the art will understand that the apparatus, system, and related methods of using the apparatus can be implemented and used without these specific details. In fact, the apparatus, system, and related methods can be implemented by improving the illustrated apparatus, system, and related methods and can be used in conjunction with any other apparatus and techniques conventionally used in the industry.
[0062] In this specification, TTFields, also referred to as alternating electric fields, are established as an anti-mitotic cancer therapy because they interfere with proper microtubule assembly during metaphase and ultimately disrupt cells during telophase and cytokinesis. Efficacy increases with increasing electric field intensity, and the optimal frequency depends on the cancer cell line, being 200 kHz, the frequency at which suppression of glioma cell growth induced by TTFields is highest. For cancer treatment, non-invasive devices have been developed with capacitively coupled transducers placed directly on the skin area close to the tumor. For patients with glioblastoma multiforme (GBM), the most common and fundamental malignant brain tumor in humans, the system for delivering TTField therapy is called the OPTUNE™ system (Novocure Ltd.).
[0063] Because the effect of TTFields is directional with cells dividing parallel to the electric field rather than those dividing in other directions, and because cells divide in all directions, TTFields are typically delivered through two pairs of transducer arrays that generate perpendicular electric fields within the tumor being treated. More specifically, for the OPTUNE system, one pair of electrodes is positioned on the left-right (LR) of the tumor and the other pair of electrodes is positioned on the anterior-posterior (AP) of the tumor. By circulating the electric field between these two directions (i.e., LR and AP), it is ensured that the maximum range of cell orientations is targeted.
[0064] Although TTFields are approved for use in specific patients, there is a need for a system that enables reliable and consistent safety testing of TTFields in animal test subjects. In studies of small animals (e.g., mice) where electrical components are connected to the animals, the animals often bite or damage the electrical components. Also, when animals are connected using cables, the animals often cause cable twisting. If such cables are provided with excessive slack, the animals can easily roll around, potentially causing damage or improper placement of the electrical components. If sufficient slack is not provided in such cables, the movement of the animals may be overly restricted. Furthermore, it can be difficult to connect electrical components to animals without significant adjustment and repositioning.
[0065] In various aspects, with reference to FIG. 1, disclosed herein is a system 10 for providing TTFields to a test subject 12 (e.g., an animal test subject such as a mouse). The system 10 can comprise one or more cage assemblies 100 for receiving and housing one or more test subjects. Some test subjects in the experimental group 14 can have attached thereto TTField therapy assemblies 200, 200', 200" (FIGS. 8, 9, and 24) that can comprise a transducer array for providing therapy to the test subject. Other test subjects in the control group 16 can have attached thereto control heater therapy assemblies 400, 400' (FIGS. 10A - 11B) that are configured to provide the same weight and heat as the TTField therapy assemblies 200, 200', 200". The plurality of TTField therapy assemblies 200, 200', 200" can be communicatively coupled to a TTField generator 18. Optionally, the TTField generator can be a generator provided as part of an INOVITRO laboratory research system (NOVOCURE GMBH). Similarly, the plurality of control heater therapy assemblies 400 can be communicatively coupled to the same or a separate TTField generator 18 (or other generator capable of initiating heat through a control heater therapy assembly as further disclosed herein). A computer 1001 can be communicatively coupled to the TTField generator 18. The computer 1001 can control the output of the TTField generator 18 and the log data from the TTField generator 18, the therapy assemblies 200, 200', 200", the control heater therapy assemblies 400, and / or the test subject 12.
[0066] The TTField treatment assemblies 200, 200', 200" and the control heater treatment assembly 400 can communicate with the TTField generator 18 via their respective cables 204 (FIG. 8). To allow the test subject to move freely within the cage assembly 100 without winding the cable 204, the cable 204 extends to a swivel portion 300 (also interchangeably referred to herein as the swivel assembly 300) and can be connected to the swivel portion 300. The swivel portion 300 further extends to the TTField generator 18 and can be connected to a second cable 20 that is connected to the TTField generator 18. Thus, as further disclosed herein, the swivel portion 300 enables electrical communication from the TTField generator 18, through the second cable 20, through the swivel assembly 300, to the cable 204 for communication with the treatment assemblies 200, 200', 200" while suppressing the winding of the cable 204.
[0067] Cage assembly Referring to FIGS. 3-5, the cage assembly 100 may include a main body 102. The main body 102 may include a floor 104 that defines a floor region having a major dimension. Optionally, the floor 104 may be rectangular or generally rectangular with corners 16. Optionally, the corners 16 may be rounded. The corners may have a radius of, for example, about 17 mm. The major dimension may be the maximum diagonal between the corners 106 of the cage. The main body 102 may further include one or more side walls 108. For example, the main body 102 may include a front side wall 108A, an opposite rear side wall 108B, and a pair of opposing side walls 108C that extend between respective edges of the front side wall 108A and respective edges of the rear side wall 108B. The intersection between each side wall may define a rounded corner 110. Optionally, the side walls 108 may converge in a direction toward the floor 104 (i.e., may slope inwardly as they extend downward) to provide a draft angle for facilitating manufacture via injection molding. Optionally, the floor may include a filling, such as sawdust, as is commonly used in conventional animal cages. Food pellets may be placed on the floor of the enclosure for feeding. A conventional water bottle may be attached to the cage to provide water to the test subject. Optionally, the cage may include an opening within each side wall of the enclosure for receiving the dispensing portion of a conventional water bottle.
[0068] In an exemplary aspect, as shown in FIG. 3, sidewall 108 may define a plurality of openings 130 for ventilation. One or more filters 132 can optionally cover the plurality of openings in each sidewall 108. A frame 134 extends around the periphery of the filter 132 and can receive fasteners (e.g., nuts 136 and bolts 138) for attachment 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 openings. Optionally, as shown in FIG. 3, a single filter 132 can cover the plurality of openings 130 (optionally, all openings) of the sidewall 108. The filter can be removable, autoclaveable, and replaceable. The filter can minimize the entry of infectious substances and agents while allowing for rapid air exchange. It is contemplated that a mesh, sieve, grating, air permeable membrane, or other permeable structure can be disposed between the plurality of openings 130 in the cage and the filter 132 to prevent the test subject from biting the filter.
[0069] As shown in FIG. 3, door 112 can be pivotally connected to main body portion 102 by a pair of hinges 114. In use, door 112 can be movable between and around (1) a closed position where door 112 cooperates with the sidewalls to provide an enclosure and (2) an open position where the door is pivoted away from the interior of the cage assembly to provide one or more openings through which access to the interior of the cage assembly can be obtained.
[0070] The cover 120 can extend across the upper part of the main body 102. The cover 120 can be releasably attached to the main body 102 via the latching part 122. The latching part 122 can be pivotally attached to the main body 102 via the hinge 124. The latching part 126, which is rotatable around the hinge 128, can be attached to the door 112. The latching part 126 can releasably engage with the capturing part at the upper part of the cover 120 to hold the door 112 in the closed position. Optionally, the cover 120 can include one or more swivel part housings 180 configured to receive at least a portion of a swivel part as further disclosed herein.
[0071] 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 main 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 for the respective test subjects 12 in each of the first enclosure and the second enclosure to communicate with each other (e.g., through vocal communication, through smell, 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 side wall and the rear side wall, and the partition 140. In these examples, it is contemplated that the floor area within each enclosure can have respective major dimensions that can be equal to the maximum diagonal between the corners of the enclosure.
[0072] The side walls (e.g., the main body 102 and the partition 140) and the cover can optionally include polycarbonate and can optionally be autoclaveable. Portions of the cage, such as the main body 102 and the cover 120, can be transparent so that the test subjects confined within the cage can be observed.
[0073] Referring to FIG. 6, the shelter sub-assembly 150 can extend inwardly from the partition 140 to each of the first enclosure 142 and the second enclosure 144. Within each enclosure, the shelter sub-assembly 150 can comprise an arcuate roof, a pair of parallel walls extending vertically downward from the arcuate roof, and optionally, a floor cover extending between the bottom edges of the side walls of the shelter sub-assembly. Within each enclosure, the shelter sub-assembly 150 can project from the partition 140 by a selected distance D. Optionally, the distance D can be about 4 to 5 centimeters. It is contemplated that the distance D can be selected such that the cable does not limit the test subject from communicating with the test subject in the opposing enclosure. For example, the cable can be strapped to the back of the test subject at a selected interval d from the head of the subject. In this way, the test subject cannot bite the cable. This selected interval also allows the test subject to enter the shelter sub-assembly before the cable touches the shelter sub-assembly. Further, the cable can be flexible enough to bend when it touches the shelter sub-assembly. The selected distance by which the shelter sub-assembly 150 projects from the partition 140 can be selected such that the test subject (e.g., at least the nose and / or face of the test subject) can at least reach the plane defined by the partition 140 when the cable is fully stretched upon hitting the shelter sub-assembly. As further disclosed herein, the cable length can be a function of the dimensions of the enclosure. Thus, the selected distance D by which the shelter sub-assembly 150 projects from the partition 140 can be a function of the cable length, the height dimension of the enclosure, and the width dimension of the enclosure.
[0074] The cover 120 for the first enclosure and the cover 120 for the second enclosure may be integrally constructed as a cover assembly 178. Optionally, the cover assembly 178 may include a swivel housing 180. In these embodiments, the cover assembly 178 can further include a swivel section 300 as further disclosed herein, and the swivel sections are disposed within their respective swivel housings 180. The cover assembly 178 may include first and second openings between the first and second enclosures and their respective swivel sections 300. The first and second openings can provide communication that can connect the cables of the treatment assembly to their respective swivel sections. Each swivel section can be in a covering relationship with each of the first and second openings. According to various embodiments, each swivel section can extend at least partially into its respective enclosure through its respective opening in the cover assembly to receive its respective cable. In a further embodiment, each cable can extend through each of the first and second openings to connect to its respective swivel section.
[0075] Referring to FIGS. 4 to 7, the distance between the cover 120 and the floor 104 can define the cage height. To prevent the test subject from having slack that can only turn over or get entangled with the cable, the cage assembly can have a selected cage height h for each enclosure, that is, a function of the length R1 and the width R2. For example, the cable 204 can have a selected length to prevent providing sufficient slack for the test subject to wrap the cable around the body of the test subject. According to some optional aspects, the dimensions of each enclosure 142, 144 can be selected such that the test subject can access the corners of the cage. However, when the test subject is placed directly below the attachment of the cable to the swivel part 300, the cable has no slack that only hangs down or only extends downward from the back of the test subject and does not touch the floor of the cage. To maximize the effective area for a given cage height, the cable can extend from directly above the center of the floor space of each enclosure. Therefore, the height of the cage can be selected as a function of the major dimension of the cage floor (for a given enclosure) and the height of the test subject. For example, the height can be selected based on the following equation. h≧(R1 2 +R2 2 -16a 2 ) / 16a Here, h is the height of the cage, R1 is the length of the enclosure, R2 is the width of the enclosure, and a is the height of the animal. Therefore, the height can be a function of the major dimension Y of the cage floor according to the following equation. h≧(Y 2 -16a 2 ) / 16a A typical test subject mouse can have a height (a) of 20 mm. Therefore, in one example, the cage height h can be a function of the major dimension Y (in millimeters) of the cage floor according to the following equation in millimeters. h≧(Y 2 -6400) / 320 [mm]
[0076] More generally, the height of the cage can be selected by multiplying a factor by the major dimension of the cage floor (of each enclosure). According to one aspect, the cage can have a height that is at least 0.5 times the major dimension of the cage floor, at least 0.6 times the major dimension of the cage floor, at least 0.7 times the major dimension of the cage floor, at least 0.8 times the major dimension of the cage floor, at least 1.1 times the major dimension of the cage floor, or at least 1.2 times the major dimension of the cage floor.
[0077] In one exemplary embodiment, the floor of the cage assembly can have a length of about 315 mm and a width of about 185 mm. Thus, if there is a partition dividing the length of the floor, 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). Thus, it is contemplated to provide a cage height that has a minimum height of at least 163 mm and is about 0.7 times the major dimension of the cage floor. 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 millimeters, between about 200 mm and about 250 mm, between about 250 mm and about 300 mm, between about 300 mm and about 400 mm, or greater than about 400 mm. In one embodiment, the cage height can be about 260 mm. In a further embodiment, 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.
[0078] It is contemplated that the above equation for selecting the cage height is not absolute because the cable has some level 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 cage height can be made smaller than the minimum height of the above equation while still providing a cage height that prevents the test subject from getting entangled.
[0079] Optionally, the cage may comprise a feeder (e.g., a food tray or a food dispenser). The feeder may optionally be connected to the partition 140 or other side walls so as to remain suspended.
[0080] Treatment assembly Referring to FIG. 8, the treatment assembly 200 may be configured to provide TTFields to a visceral tumor. The treatment assembly 200 may comprise a flexible circuit board 202 having a connector end 206 and one or more lead ends 208 at the ends of respective electrical leads 205 opposite the connector end 206. The electrical leads 205 may be provided as components of a cable 204. Optionally, the flexible circuit board 202 may be configured to connect to the swivel portion 300. The cable 204 may be elongate and have sufficient flexibility to allow a twist of a certain magnitude without requiring a swivel portion. The connector end 206 may optionally be a USB-C connector (e.g., a male USB-C connector). The use of a flexible circuit board 202 as disclosed herein to provide a plurality of electrical leads 205 as part of an integrated structure, thereby avoiding cable or wire entanglement and minimizing the space occupied by the electrical leads, is contemplated. Thus, in one aspect, the cable 204 may be defined by a portion of the flexible circuit board 202.
[0081] In a pre-use configuration, as shown in FIG. 8, the lead ends 208 may be spaced 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 can be arranged in two rows of four lead ends, with the two rows extending along the longitudinal dimension 201. As another example, one or more longitudinally extending rows may comprise a single row of lead ends 208. However, it is contemplated that any desired arrangement of lead ends may be used. The cable 204 may extend perpendicular or substantially perpendicular to the longitudinal dimension 201.
[0082] Each lead wire end 208 can be configured to engage or connect with a respective plate 210. Thus, the treatment assembly 200 can include a plurality of electrodes, each electrode including a lead wire end 208 that is in contact with or connected to a respective plate 210. In certain potential embodiments, at least one (optionally, each) plate 210 can be a ceramic plate. In other embodiments, it is contemplated that at least one (optionally, each) plate can be a glass plate, such as where the treatment assembly 200 functions as a control heating device. In yet further aspects, other types of electrodes are contemplated, such as electrodes formed from metal or other conductive materials.
[0083] 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 and breathable adhesive, such as, for example, polyurethane. In certain 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 that pass through the inner layer 212 for receiving respective plates 210. The openings 218 can be longitudinally spaced along the inner layer. Although described as receiving individual plates, it is contemplated that each opening can optionally receive a plurality of plates (e.g., two plates).
[0084] The plate 210 can have an upper surface 220 and a lower surface 222. The upper surface can be disposed against the lead wire end 208. A layer of hydrogel 224 can be disposed in contact with each lower surface 222 of the plate 210. The layer of hydrogel 224 can optionally cover at least two adjacent plates 210. Optionally, the layer of hydrogel 224 can cover the lower surface 222 of the plate 210 and an adjacent portion of the inner surface of the inner layer 212. The layer of hydrogel 224 can, in certain optional aspects, be about 0.6 mm thick. The hydrogel 224 can include, for example, an AG625 sensitive gel made by AXELGAARD.
[0085] The cover layer 230 can adhere to the outer surface 214 of the inner layer 212. The cover layer 230 can cover the plurality of lead wire ends 208 of the flexible circuit board 202. The cover layer 230 can include one or more tab portions that extend beyond the periphery of the inner layer 212. For example, the cover layer 230 can include two opposing tab portions 232 that are complementary to each other when the cover layer defines a circumferential ring (e.g., when wrapped around the torso of a test subject as further disclosed herein). Optionally, the tab portions 232 can be about half the width of the cover layer, in which case they intersect the main body portion of the cover layer. When the cover layer is wrapped around the torso of the test subject, the tab portions 232 can extend over each other to adhere to respective portions of the cover layer at the ends of the cover layer opposite the respective tab portions.
[0086] In an optional aspect, the cover layer can have an inner surface that includes a biocompatible non-woven adhesive. The non-woven adhesive can optionally be elastic in the longitudinal dimension 201. In some embodiments, the cover layer can comprise a medical non-woven tape with product number 1776 made by 3M.
[0087] The release layer 250 can contact and cover the underside of the biocompatible and breathable polyurethane adhesive on the inner surface 216 of the inner layer 212 and the underside of the hydrogel layer 224. The release layer can protect the adhesive before the therapeutic assembly is attached to the test subject. The release layer 250 can have a shape that is complementary to the shape of the cover layer 230. The release layer can include a separate tab 252 configured to cover the tab portion 232 of the cover layer 230.
[0088] The treatment assembly may include at least one temperature sensor 260, such as a thermistor or a thermocouple (not shown, but the temperature sensor 260 may be located at positions corresponding to the temperature sensors 414 and 414' in FIGS. 10B and 11B). The at least one temperature sensor may optionally be integral with the flexible circuit board 202. The at least one temperature sensor may comprise a plurality of temperature sensors. For example, the temperature sensors may be disposed on the flexible circuit board 202 proximate to each lead wire end 208. The temperature sensor 260 can provide feedback to prevent overheating of the treatment assembly or causing burns to the test subject. For example, based on a temperature reading from the temperature sensor 260 that exceeds a threshold value (e.g., 40° C.), the TTField generator 18 can adjust or stop the induction of TTField at one or more electrodes. Also, the system 10 can receive feedback from the temperature sensor 260 to maintain a consistent temperature in the control heater treatment assembly further disclosed herein. Optionally, the temperature sensors can be disposed in respective holes in each plate to measure the temperature between the plate and the hydrogel. In a further aspect, the temperature sensors may be disposed on the side of each plate opposite the hydrogel, thereby avoiding the need to form holes in the plate (and potentially making the plate unnecessarily fragile). In a further embodiment, the temperature sensors can be disposed in the hydrogel portion on the side surface of each plate (e.g., within 3 millimeters of the edge of the plate). For example, as shown in FIG. 10A, a pair of plates 412 may share a single layer of hydrogel 410, and each temperature sensor may be disposed between each pair of plates.
[0089] The portion of the treatment assembly that presses on the test subject (e.g., excluding the weight of the cable) can optionally be a weight of less than about 10% of the weight of the subject. For example, for a typical mouse, the portion of the treatment assembly that presses on the test subject can be a weight of less than about 2.5 grams.
[0090] The treatment assembly can be flexible enough to conform to a portion of the torso of test subject 12. Optionally, in a pre-use configuration as shown in FIG. 8, the treatment assembly has a length in a longitudinal dimension 201 that is sufficient to extend around the torso of the test subject (when placed on the animal and during use). Optionally, the treatment assembly can be pre-formed into a three-dimensional shape configured to be complementary to the shape of the torso of test subject 12.
[0091] Optionally, the kit can include a plurality of treatment assemblies 200 having various lengths in the longitudinal dimension 201 (in the pre-use configuration). In this way, a test subject can have an appropriately sized treatment assembly attached (depending on the circumference / around the torso of the animal). For example, an appropriately sized treatment assembly can fit snugly around the torso of the test subject. Optionally, an additional cover material (which can be the same material as the outer layer, for example) can be provided to reinforce attachment to the test subject and to seal the edges of the adhesive material from dirt and debris that could interfere with good contact.
[0092] Referring to FIG. 9, the treatment assembly 200' can be configured to treat a subcutaneous tumor. The treatment assembly 200' has a structure generally similar to that of the treatment assembly 200 and has an inner layer 212' that defines an opening 218' for receiving a plate 210'. Optionally, it is contemplated that a hydrogel 224' can be received within the opening 218'. A flexible circuit board 202' can include a cable 204', a connector end 206' configured to connect to the swivel portion 300 (FIG. 1), and one or more lead wire ends 208' at a lead wire end opposite the connector end 206'. The lead wire ends 208' can be configured to connect to respective plates 210'. An outer layer 230' can be attached to respective upper surfaces of the inner layer and the lead wire ends. A release layer 250' with a separate tab 252' can be attached to the underside of the inner layer 212' and the hydrogel 224'. The outer layer 230' and the release layer 250' can have a structure similar to the outer layer 230 and the release layer 250.
[0093] 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' (other than the inner release layer if present) and is configured to receive a subcutaneous tumor. Optionally, the through hole 270' can have a diameter between 10 mm and 15 mm. Optionally, the through hole 270' can have a maximum diameter of about 15 mm. A cap 272' can extend across the through hole 270' and define a receiving portion 274' configured to receive an outwardly extending portion of the subcutaneous tumor. The cap 272' can be attached to the cover layer 230'. For example, the cap 272' can define a radially extending periphery 276'. An adhesive ring 278' can engage the flange 276' and the outer layer 230' to secure the cap 272' to the outer layer. The cap 272' can prevent dirt and debris (e.g., sawdust floor covering) from entering the hole and can prevent contact between the treatment assembly and the test subject.
[0094] In an exemplary embodiment, the opening 218' through which the plate 210' is received can have a predetermined relationship to the through hole 270'. Optionally, in these embodiments, as shown in FIGS. 9 and 11A, the opening 218' can be circumferentially spaced around the periphery of the through hole 270' (and thus, when the tumor extends through the through hole 270', around the periphery of the subcutaneous tumor).
[0095] According to one aspect, the kit can include a plurality of treatment assemblies 200' having through holes 270' of various diameters and corresponding caps 272' of various sizes. The plurality of treatment assemblies 200' having through holes of various diameters can optionally have corresponding various spacings between the lead wire ends 208' and the plate 210'. In this way, a treatment assembly 200' sized to fit the subcutaneous tumor of the test subject 12 can be attached to the test subject 12. Optionally, the kit can further include a plurality of caps (optionally of the same size and / or of various sizes) such that the caps can be exchanged over the course of the treatment.
[0096] The lengths of cables 204, 204' can be selected based on the dimensions of the enclosure such that test subject 12 cannot be wound by the cables or become entangled with the cables. An amount of slack can be attached to the back of the test subject to reduce the amount of free length of the cable. Thus, the cable can have an operating portion that is not attached to the test subject, and the operating portion can define the operating length of the cable. According to one aspect, the operating length of the cable can be selected such that when the test subject is directly below the swivel portion, the cable does not have a length that hangs from the back of the test subject and touches the floor. Thus, the maximum operating 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 portion) plus twice the height of the test subject. In a further aspect, the cable length can be selected such that the cable does not have a slack that allows it to hang from the back of the test subject within the threshold distance t (FIG. 6) from the floor of the cage. Thus, the maximum operating length of the cable can be approximated by adding twice the height of the test subject to the height from the floor when the cable is attached to the swivel portion and subtracting twice the threshold distance. Optionally, the threshold distance can be 0 millimeters, 1 millimeter, 2 millimeters, 4 millimeters, 6 millimeters, 10 millimeters, or greater. In one aspect, the threshold distance can be in the range from about 1 mm to about 10 mm, or from about 2 mm to about 6 mm. Due to the limited flexibility of the cable, it is still being further considered that the length of the operating portion of the cable can be slightly longer than the sum of twice the height of the subject and the height of the cable without the cable being able to reach the floor of the cage.
[0097] To construct the treatment assembly 200, each of the plurality of plates 210 can be disposed within the openings in the inner layer of the treatment assembly. For example, in certain embodiments, pairs of plates can be disposed within each opening. Alternatively, a single plate can be disposed within each opening. Each of the plurality of lead wire ends can be disposed in contact with a respective one of the plurality of plates. As previously described, the lead wire ends form respective electrodes when connected to the plates as disclosed herein. A cover layer can be attached to the outer surface of the inner layer so as to cover the plurality of electrodes. A layer of hydrogel can be applied to the lower surface of each of the plurality of plates. In one aspect, a pair of plates disposed within a common opening in the inner layer can also share a layer of hydrogel. Optionally, the hydrogel can be applied across adjacent portions of the inner surface of the inner layer.
[0098] Referring to FIGS. 24 - 29, in a further aspect, it is contemplated that the treatment assembly 200" can be configured such that at least a portion thereof is disposed on the head of a test subject. For example, the head covering portion 9a of the treatment assembly 200" can be connected to at least a portion of the head of a mouse, as shown in FIG. 26. The head covering portion 9a of the treatment assembly 200" can include a head - wearable layer 6 that extends across a portion of the head of the test subject and is configured to be connected to the test subject through an adhesive disposed on one or more of its inner surfaces. The treatment assembly 200" can further include a torso covering portion 9b that is configured to be disposed on the body (e.g., torso) of the test subject (e.g., wrapped around the body / torso of the test subject as further disclosed herein). The torso covering portion 9b of the treatment assembly 200" can include an inner adhesive - wearable layer 1 that is configured to engage the body (optionally, the skin) of the test subject. A flexible circuit board 5 can include a plurality of lead wire ends. An end 8 of the flexible circuit board can communicate with the TTField generator 18 (FIG. 1). An inner adhesive patch 4 can be connected to the skin - engaging side of the adhesive portion 6 with a portion of the flexible circuit board 5 disposed therebetween. An outer - wearable layer 7 can be connected to the outer side of the torso covering portion 9b of the treatment assembly.
[0099] The plate (for example, a ceramic plate) 3 can be connected to the lead wire end of a flexible circuit board. The hydrogel 2 can be disposed under the ceramic plate so as to engage with 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) for receiving the corresponding portion of the hydrogel 2.
[0100] The flexible circuit board 5 can include a plurality of lead wire ends (and corresponding plurality of electrodes 602) configured to be disposed on the head of the test subject, and one or more lead wire ends (e.g., two lead wire ends) (and corresponding plurality of electrodes 604) configured to be disposed on the body (e.g., torso) of the test subject. In an exemplary embodiment, the plurality of lead wire ends (for placement on the head) are configured to be under the head-wearable layer 6, and the one or more lead wire ends (for placement on the torso) are configured to be under the outer wearable layer 7 of the torso covering portion 9b, and each lead wire end covers its respective ceramic plate 3 and hydrogel portion 2. Optionally, the plurality of lead wire ends configured to be disposed on the head of the test subject can include a first group of lead wire ends (e.g., three lead wire ends corresponding to electrode 602a) configured to be disposed on a first side of the head of the test subject (with respect to the midplane 606 that bisects the test subject into left and right sides), and a second group of lead wire ends (e.g., three lead wire ends corresponding to electrode 602b) configured to be disposed on a second, opposite side of the head of the test subject (with respect to the midplane). The one or more lead wire ends configured to be disposed on the body (e.g., torso) of the test subject can include a first lead wire end (corresponding to electrode 604a) disposed on a first side of the body of the test subject with respect to the midplane, and a second lead wire end (corresponding to electrode 604b) disposed on a second side of the body of the test subject with respect to the midplane. Referring to FIG. 28, it is contemplated that the first lead wire end disposed on the first side of the body can cooperate with the second group of lead wire ends on the second side of the head of the test subject to provide a TTField, and the second lead wire end disposed on the second side of the body (torso) can cooperate with the first group of lead wire ends on the first side of the head of the test subject to provide a TTField. The TTField can be provided in an alternating manner to provide or facilitate the intersection of the TTFields.
[0101] In an exemplary aspect, the flexible circuit board 5 can include undulations (e.g., switchbacks), meanders, waves, or zigzags (generally referred to as "alternating shape portions" 700) configured to promote flexibility and allow its head portion to move relative to the test subject. During use, the alternating shape of this portion of the flexible circuit board 5 can provide a reduction in starting length (avoiding unnecessary slack in the cable), while also allowing for an increase in length and straightening to accommodate movement of the test subject (e.g., neck extension, torsion, and rotation). In these aspects, as shown in FIGS. 24-25 and FIGS. 27-29, the alternating shape portion can be disposed between the head covering portion 9a and the torso covering portion 9b. It is further contemplated that the alternating shape portion of the flexible circuit board 5 can be disposed between a plurality of lead wire ends (for placement on the head) and at least one lead wire end (for placement on the torso).
[0102] Exemplary non-limiting dimensions of the treatment assembly 200" are provided in millimeters in FIG. 29.
[0103] It has been considered that the material and properties of the inner adherable layer 1 of the body covering portion 9b may be the same as or similar to the material and properties of the cover layer 212, 212' disclosed herein with respect to the treatment assemblies 200, 200'. Similarly, it has been considered that the material and properties of the hydrogel 2 of the treatment assembly 200" may be the same as or similar to the material and properties of the hydrogels 224, 224' disclosed herein with respect to the treatment assemblies 200, 200'. Further, it has been considered that the material and properties of the plate 3 of the treatment assembly 200" may be the same as or similar to the material and properties of the plates 210, 210' disclosed herein with respect to the treatment assemblies 200, 200'. Furthermore, it has been considered that the material and properties of the flexible circuit board 5 may be the same as or similar to the material and properties of the flexible circuit boards 202, 202' disclosed herein with respect to the treatment assemblies 200, 200'. Still further, it has been considered that the material and properties of the headwearable layer 6 and the outer wearable layer 7 of the treatment assembly 200" may be the same as or similar to the material and properties of the cover layer 230 / outer layer 230' disclosed herein with respect to the treatment assemblies 200, 200'.
[0104] Referring to FIGS. 10A to 11B, the control heater treatment assembly 400 can be connected to a control test subject and can be configured to mimic many, all, or substantially all of the aspects of the treatment assembly 200. Similarly, the control heater treatment assembly 400' can be configured to mimic all or substantially all of the aspects of the treatment assembly 200' and can have a structure and operation similar to those described for the control heater treatment assembly 400. Similarly, the control heater treatment assembly can be configured to mimic all or substantially all of the aspects of the treatment assembly 200" and can have a structure and operation similar to those described for the control heater treatment assembly 400. For example, the control heater treatment assembly 400 can be configured to generate heat to maintain a similar temperature against the skin of the control test subject, thereby suppressing the differences between the properties of the control group and the test group. As another example, the control heater treatment assembly 400 can be configured to have substantially the same or generally the same weight as a treatment assembly that can generate TTFields as further disclosed herein.
[0105] The control heater assembly 400 may comprise a flexible circuit board 402. The flexible circuit board 402 may comprise a cable 404 and a connector end 406 configured to couple to the swivel unit 300. The flexible circuit board may comprise a plurality of resistive heaters disposed at locations corresponding to where the electrodes are positioned in the treatment assembly 200. For example, the flexible circuit board 402 may comprise eight zones 410 (e.g., two columns of four zones 410) where the electrodes may be in the corresponding treatment assembly. More generally, the flexible circuit board 402 can have any desired number of zones, each zone corresponding to the location of the electrodes in the corresponding treatment assembly. Optionally, each zone 410 can comprise two resistive heaters 412 (schematically shown as a single unit disconnected from the circuit board 402 in FIG. 10A and shown in detail as components of the circuit board 402 in FIG. 11). Temperature sensors 414 may be disposed in each zone 410 and, optionally, may be disposed at the center of each zone 410 equally spaced between the heaters 412. The heaters 412 may optionally comprise a glass plate.
[0106] Optionally, the control heater assembly 400 may comprise an inner layer 420 defining a plurality of through-holes through which the heaters 412 may be disposed. Optionally, the control heater assembly 400 may comprise a cover layer 430 extending across the upper side of the flexible circuit board. A release liner 440 may be removably attached to the lower surface of the inner layer. The inner layer 420 and the cover layer 430 may have the same material and the same shape as the corresponding treatment assembly to feel the same to the test subject. Optionally, a layer of hydrogel 416 may cover the lower side of the flexible circuit board 402. Similarly, a control heater assembly 400' can have a structure corresponding to the structure of the treatment assembly 200' and include a flexible circuit board 402', an inner layer 420', a release liner 440', a cover liner 430', a cap 450', and an adhesive ring 460'. Similarly, control heater assemblies that mimic the form, weight, heat, and other perceived experiences of the treatment assembly 200" are being further considered.
[0107] The control heater assembly 400 can be connected to the TTField generator 18 via the swivel unit 300. The swivel unit 300 can control the output of the resistive heater 412 based on feedback from the temperature sensor 260. In certain embodiments, the control heater assembly 400 can maintain a set temperature (e.g., 38.5 °C or 39 °C) so as to mimic the temperature reached as a side effect where the corresponding treatment assemblies 200, 200', 200" provide TTField. In further embodiments, the control heater assembly 400 can be selectively controlled so as to maintain a temperature that matches the temperature of the treatment assembly in the corresponding test subject receiving TTField treatment.
[0108] The control heater assemblies 400, 400' can further have a weight similar to the weight of their respective treatment assemblies 200, 200', 200". Thus, the control heater assemblies can create an experience that is similarly perceived in the test subject. In this way, the effect of TTField on tumor growth can be separated from other characteristics of the test procedure.
[0109] In an exemplary aspect, a kit can be provided that has both the control heater assemblies 400, 400' and the treatment assemblies 200, 200', 200". In these aspects, it is contemplated that each treatment assembly in the kit having a corresponding / mate control heater assembly disposed within the same kit, thereby maximizing the uniformity between the control group and the experimental / treatment group.
[0110] It is contemplated that the embodiments disclosed herein can be used to provide other currents, electric fields, and heat to different body parts of a test subject in addition to providing TTField.
[0111] In some optional embodiments, a thick treatment assembly (and corresponding control heater assembly) for a test subject with a thick torso may have a length of from about 200 mm to about 250 mm (with respect to the longitudinal axis 201), a width of from about 100 mm to about 130 mm (optionally from about 110 mm to about 115 mm), and a thickness of from about 1.6 mm to about 1.7 mm. In certain optional embodiments, a thin treatment assembly (and corresponding control heater assembly) for a test subject with a thin torso may have a length of from about 200 mm to about 250 mm, a width of from about 80 mm to about 115 mm (optionally from about 100 mm to about 110 mm), and a thickness of from about 1.6 mm to about 1.7 mm. In a further optional embodiment, a treatment assembly (and corresponding control heater assembly) for a subcutaneous tumor may have a length of from about 290 mm to about 330 mm, a width of from about 65 mm to about 95 mm, and a thickness of from about 1.6 mm to about 1.7 mm.
[0112] Ring body It has been considered that a test subject may tend to bite or chew through treatment assemblies 200, 200', 200" or control heater treatment assemblies 400, 400'. Referring to FIGS. 30 - 32, it has been considered that in order to suppress such behavior, the ring body 500 may be in a ring shape. Optionally, the ring body 500 may have two opposite ends that are integrally connected to form the ring shape. For example, the ring body 500 may include a protrusion 502 disposed at a first end 506 and configured to be received into one or more holes 504 at an opposite second end 508. The protrusion 502 may have an enlarged distal end with a diameter larger than the diameter of one or more of the holes 504 so that it cannot accidentally come off (due to an expansion between the surface of the protrusion and a portion of the second end defining the hole) when inserted into the hole. In order to adapt the ring body to test subjects of different sizes, it has been considered that one or more holes 504 may comprise a plurality of holes 504 spaced around the perimeter of the ring body 500 such that the ring body may have a selectable operating diameter depending on the hole into which the protrusion 502 is inserted.
[0113] Optionally, the annular body 500 may have an inner surface 510 that is serrated, sawtooth-shaped, or toothed. Optionally, the annular body 500 may have an outer surface 512 that tapers axially. The annular body 500 may be oriented such that the outer surface tapers in a direction away from the head of the test subject.
[0114] It has been considered that both the excessive weight of the annular body and the sound reflection may shorten the life of the test subject. Thus, in one aspect, the annular body 500 may optionally define a plurality of holes 514 that may extend axially through the entire annular body (through the thickness of the annular body). The holes 514 can reduce the amount of material and thus the weight of the annular body and minimize sound reflections that may cause stress to the test subject.
[0115] The annular body 500 may optionally be flexible. Optionally, the annular body may include a polymer such as silicone.
[0116] Swing assembly Referring to FIGS. 12 and 15, the swing unit 300 may be mounted on the cover 120 within the swing unit housing 180. The swing unit housing 180 may include a side wall 182 that is integral with the cover 120. The swing unit housing 180 can receive a removable inner circumferential insert 184. The swing unit housing may further include an upper cover 186 that couples to the side wall 182.
[0117] The swivel unit 300 may include a damping plate 302 that attaches to the upper cover 186 via screws or other fasteners. The upper cover 186 may be part of the swivel unit module. The damping plate 302 can be connected to the motor mounting plate 304 via screws 306. The swivel unit 300 can have a central axis 308, and the motor 310 can rotate around the central axis 308. The motor 310 can be connected to the motor mounting plate 304 via screws 312. A rotatable base 314 can be attached to the motor 310 via screws 316. Thus, the rotatable base can be made rotatable relative to the motor mounting plate 304 via the motor. The bearing housing 316 can be connected to the rotatable base 314 via standoffs 318. The rotatable base 314 can define a dependent tab 320 that can be connected to a flexible circuit assembly 322.
[0118] In certain optional aspects, the upper cover 186 may include at least one input device (e.g., a button) configured to initiate and stop therapy (e.g., TTFields or heat). Optionally, the at least one input device can include a plurality of input devices, each configured to control the operation of different components of the system. In one aspect, each input device can be configured to control the application of TTFields and the application of heat. In a further aspect, the input device can be configured to initiate and stop the operation of the swivel unit. In a further aspect, the upper cover 186 may include a display configured to indicate information such as, for example, experimental identification information (e.g., cage number, type of electrode), or operating mode (e.g., standby, therapy, heat, pause). In various aspects, the upper cover 186 can provide a communication port that can communicate with the swivel unit 300 to provide communication between the signal generator 12 (FIG. 1) and the therapy / control heater assembly.
[0119] Referring also to FIGS. 13 and 15, the flexible circuit assembly 322 can include a printed circuit board (PCB) 324 to which an input / output connector 326 is attached. The connector 326 can provide communication above the swivel portion. The printed circuit board 324 can define a patterned portion 328 that extends between a base portion 330 and a cable connector end 332. The patterned portion 328 can have a structure that allows the printed circuit board 324 to be twisted so that the connector end 332 can pivot relative to the base portion 330, as further described herein. In an exemplary embodiment, the patterned portion 328 can have a meandering, wavy, zigzag, or undulating pattern. A pair of sensor connector portions 334 can extend from the base portion 330.
[0120] Referring also to FIGS. 18A, 18B, and 19, the bearing housing 316 can accommodate a bearing 340 (e.g., a ball bearing or a nylon bearing) that can receive and support a pivot body 342 within an inner raceway ring. The pivot body 342 can define a slot 344 that can receive the connector end 332 of the printed circuit board 324. The slot 344 can receive and engage the connector end 332 so that the connector end pivots about the central axis 308 and the pivot body pivots correspondingly. (The figure shows the connector end 332 remaining in a predetermined position when the pivot body pivots, but it should be understood that during use, the connector end can pivot with the pivot body.) The pivot body 342 can define a cantilever tab 346 that extends parallel to the central axis 308.
[0121] A centering spring 348 can extend from a standoff 350 attached to the bearing housing 316 to engage a protrusion 352 or other radially extending surface that extends away from or spaced from the central axis 308 of the swivel portion 300. The centering spring 348 can bias the pivot body 316 to a neutral position 354. During use, the pivot body can be in the neutral position 354 when no torque or substantially no torque is applied to the printed circuit board 324.
[0122] Referring to FIGS. 15, 18A, 18B, and 19, a pair of sensors 356 (e.g., electro-optical sensors such as VISHAY TCPT1600X01 sensors) can be attached to the bearing housing 316 via respective sensor mounting portions 358. The sensors 356 can communicate with the PCB 324 at the sensor connector portion 334. The sensors 356 can communicate with a processing device (e.g., a PLC control device on a circuit board 359 as shown in FIG. 23). The sensor can have a light source, a light detector, and an optical path between the light source and the light detector. The sensors 356 can be arranged such that the cantilever tabs 346 obstruct both sensors 356 when the pivot body 316 is in the neutral position. When the test subject walks within the cage, it can twist the cable 204 (FIG. 8), thereby applying torsion to the pivot body 342 and pivoting the pivot body from its neutral position. When the pivot body pivots sufficiently from the neutral position 354 in the first direction 360 (see FIG. 19), the cantilever tab 346 moves outside the optical path of the first sensor 356A, and the first sensor can detect light from the light source at the light detector. In this way, the swivel unit 300 can detect torsion of the cable in the first direction. The processing device can rotate the motor 310 in the first direction 360 to relieve the torsion in the cable. Optionally, the swivel unit can be configured to remain stationary until a minimum threshold angle is reached from the neutral position 354 to prevent excessive movement that could cause wear to the motor. Optionally, the motor can rotate at a minimum angular distance to minimize an excessive number of small movements. Similarly, when the pivot body pivots sufficiently from the neutral position 354 in the second direction 362 (opposite to the first direction), the second optical sensor 356B can detect such a condition, and the processing device can rotate the motor in the second direction to relieve the torsion in the cable. In this way, the swivel unit can limit the amount of torsion in the cable 204, thereby enabling free movement of the test subject within the cage.
[0123] The restricting part 364 can adhere to each sensor mounting part 358. Each restricting part 364 can include a central direction extending part that can act as a stopping part for preventing the pivoting body from pivoting beyond the threshold angle from the neutral position 354, thereby preventing the printed circuit board 324 from being damaged.
[0124] The pivoting body 342 can define a connector 380 configured to receive the connector ends 206, 206', 406, 406' of the flexible circuit board and electrically connect the flexible circuit board to the PCB 332. For example, the connector 380 can include a USB-C connector that is complementary to the connector end of a flexible circuit board (e.g., a female USB-C connector). Optionally, the connector 380 may include a CAN bus connection.
[0125] The swivel part can include a slip ring that enables communication between the treatment assembly 200 (or treatment assembly 200' or treatment assembly 200") and the heater assembly 400 (or heater assembly 400') and the TTField generator 18 by maintaining electrical communication through the swivel part. The slip ring can enable communication of at least 20 communication channels.
[0126] Computer device 1001 can communicate with the swivel unit 300 (e.g., through cable 20 or other cables) to track and / or record various measurement criteria. In a further aspect, computer device 1001 can be embodied as a control device in PCB 359 (FIG. 23). For example, the measurement criteria can include the following measurement criteria, namely, the number of rotations, the number of rotations in a first selected period, the frequency of motor operation, the frequency of motor operation in a second selected period, the number of motor operations including a change in direction, the number of motor operations including a change in direction in a third selected period, the period of a constant operation, and some or all of the log of motor operations and the corresponding time of motor operations. Such measurement criteria can indicate abnormal behavior in the test subject. Further, such measurement criteria can indicate a malfunction of the swivel unit 300. In one aspect, a warning (e.g., a warning light or an audible warning) can be activated to notify the user that the swivel unit 300 is malfunctioning or that the test subject is behaving abnormally. In a further aspect, a computer device or control device communicating with the swivel unit can be configured to receive user input. The user input can define one or more thresholds, such as a frequency threshold (e.g., the frequency of a change in the direction of rotation) or a time threshold (e.g., the period of a constant rotation threshold). A warning can be activated when each threshold is exceeded.
[0127] In a further aspect, the computer device can generate and output a log report comprising at least one of the collected measurement criteria. The log report can further output a comparison of the measurement criteria based on a comparison with an average measurement criterion. The average measurement criterion can be an average measurement criterion for similar test subjects, or an average measurement criterion for a given subject over a selected time period (e.g., over the course of time, days, or weeks). For example, the average measurement criterion can include an average amount of movement that a test subject makes each day. Thus, it is contemplated that a decrease in the daily amount of movement may indicate a deterioration of the health of the test subject. It is further contemplated that an overly high or overly low amount of movement compared to other similar test subjects can indicate the relative health of the test subject. It is further contemplated that monitoring various measurement criteria can be made possible by the identification of changes to confirm that an animal test subject survives beyond the end of the experimental period.
[0128] Referring to FIG. 1, a respective treatment assembly can be attached to a plurality of test subjects 12 in experimental group 14. The treatment assembly can be selected to treat a specific tumor (e.g., treatment assembly 200 for an organ tumor or treatment assembly 200' for a subcutaneous tumor). The treatment assembly can be of an appropriate size. For example, for an organ tumor, the longitudinal length of the treatment assembly can be appropriate to comfortably wrap around the circumference of the test subject's torso along the torso in a given tumor. For a subcutaneous tumor, the through holes and caps of the treatment assembly can be selected to fit the subcutaneous tumor with a minimum of excess space. The length of the cable of the treatment assembly can be selected, as disclosed herein, to allow the test subject to freely move through the floor area of the enclosure while not providing an excessive length that could become entangled. The release liner can be removed so that the adhesive can engage the skin of the test subject. The hair of the test subject can be removed in the application area by a trimming device and / or a depilatory cream (e.g., VEET depilatory cream). Similarly, a respective control heater treatment assembly 400 or control heater treatment assembly 400' can be attached to the test subjects 12 in the control group (to match the experimental group).
[0129] The treatment assembly can be placed on the body such that the electrodes are placed as close as possible to the tumor. In various embodiments, the treatment assembly (or control heater assembly) can be placed on the body of the test subject so as to minimize or eliminate interference with natural movement. For example, the treatment assembly can be placed away from the hind or front limbs of the mouse to allow natural movement. The treatment assembly can be selected based at least in part on the size of the mouse. For example, a thin treatment assembly can be placed on a mouse weighing less than 23 grams, and a thick treatment assembly can be placed on a mouse weighing more than 23 grams.
[0130] The treatment array (or control heater assembly) can be oriented such that the cable extends towards the buttocks / hip of the test subject. It has been considered that the subcutaneous treatment assembly and the control heater assembly can have a bend (e.g., a 90-degree bend) formed that extends the cable to the middle of the back of the test subject and then along the back towards the buttocks. The formation of the bend can be provided in either direction depending on the side of the test subject where the subcutaneous tumor is located. An adhesive (e.g., a bandage) may be placed on the test subject to enhance the attachment of the treatment assembly (or control heater assembly).
[0131] The test subject can be placed in each enclosure of the cage assembly. The connector ends of each treatment assembly and the control heater treatment assembly 400 can be attached to their respective swivel parts.
[0132] The treatment assembly can be controlled to provide TTFields to a subject. For example, referring to FIGS. 20 and 21, TTFields of 50-500 kHz (optionally, 150-500 kHz) can be delivered to an organ tumor 22 (FIG. 20) or a subcutaneous tumor 22' (FIG. 21). Optionally, the TTFields can be delivered continuously along another axis of propagation (to provide an alternating electric field). For example, a first pair of opposing electrodes can apply a first electric field across the tumor along a first axis of propagation 60. A second pair of electrodes arranged to have a second axis of propagation 62 that is perpendicular or substantially perpendicular to the first axis of propagation can alternate with the first pair of opposing electrodes to provide an alternating electric field across the tumor. For the treatment assembly 200, each electrode can cooperate with a respective electrode located farthest from it (e.g., on the other side of the subject's body) to provide an alternating TTField. Optionally, each electrode can be independently controlled to provide a specially tailored treatment. The control heater treatment assembly can be controlled via a TTField generator or other control device to provide RF heating to match or substantially match the temperature of the treatment assembly. The treatment can optionally continue for about 1-2 weeks.
[0133] The tumors of the experimental group and the control group can be compared during and after treatment. For example, for subcutaneous tumors, while the treatment assembly is attached to the subject's body, the cap can be removed to expose the subject, and the size of the tumor can be measured with calipers. Organ tumors can be measured, for example, via magnetic resonance imaging (MRI), ultrasound (US), or computed tomography (CT) scans. The treatment assembly can be removed prior to such scans.
[0134] Computer device FIG. 22 shows a system 1000 including an exemplary configuration of a computer device 1001 for use in the system 10.
[0135] The computer device 1001 may include one or more processing units 1003, a system memory 1012, and a bus 1013 that couples various components of the computer device 1001, including the one or more processing units 1003, to the system memory 1012. In the case of multiple processing units 1003, the computer device 1001 can utilize parallel computing.
[0136] The bus 1013 may comprise one or more of several possible types of bus structures, such as a memory bus, a memory controller, a peripheral bus, an accelerated graphics port, and a processor or local bus using any of a variety of bus architectures.
[0137] The computer device 1001 can operate in and / or include various computer-readable media (e.g., non-transitory). The computer-readable media can be any available media that is accessible by the computer device 1001 and includes non-transitory, volatile, and / or non-volatile media, removable and non-removable media. The system memory 1012 includes 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 providing software 1006 that are accessible by and / or operable by one or more processing units 1003.
[0138] Computer device 1001 may include other removable / non-removable, volatile / non-volatile computer storage media. The mass storage device 1004 can provide non-volatile storage of computer code, computer-readable instructions, data structures, program modules, and other data for the computer device 1001. The mass storage device 1004 can be a hard disk, a removable magnetic disk, a removable optical disk, a magnetic cassette or other magnetic storage device, a flash memory card, a CD-ROM, a digital versatile disk (DVD) or other optical storage, a random access memory (RAM), a read-only memory (ROM), an electrically erasable programmable read-only memory (EEPROM), etc.
[0139] Any number of program modules can be stored on the mass storage device 1004. The operating system 1005 and the TTField providing software 1006 can be stored on the mass storage device 1004. One or more (or some combination thereof) of the operating system 1005 and the TTField providing software 1006 can include a program module and the TTField providing software 1006. The temperature data 1007 can also be stored on the mass storage device 1004. The temperature data 1007 may be stored in any one of one or more databases known in the art. The database may be centralized or distributed across multiple locations within the network 1015.
[0140] A user can input instructions and information into computer device 1001 using an input device (not shown). Such input devices include, but are not limited to, keyboards, pointing devices (e.g., computer mice, remote controls), microphones, joysticks, scanners, gloves and other tactile input devices covering the body, motion sensors, etc. These and other input devices can be connected to one or more processing devices 1003 using a human-machine interface 1002 connected to bus 1013, but can also be connected by other interfaces and bus structures such as parallel ports, game ports, IEEE 1394 ports (also known as Firewire ports), serial ports, network adapters 1008, and / or universal serial buses (USB).
[0141] Display device 1011 may be connected to bus 1013 using an interface such as display adapter 1009. It is contemplated that computer device 1001 may have two or more display adapters 1009, and that computer device 1001 may have two or more display devices 1011. Display device 1011 may be a monitor, LCD (liquid crystal display), light emitting diode (LED) display, television, smart lens, smart glass, and / or projector. In addition to display device 1011, other output peripheral devices may include components such as speakers (not shown) and printing devices (not shown) that can be connected to computer device 1001 using input / output interface 1010. Any step and / or result of the method can be output to the output device in any form (or caused to be output). Such output can be in any form of visual representation including, but not limited to, text, graphics, animation, sound, touch, etc. Display unit 1011 and computer device 1001 can be part of one device or separate devices.
[0142] The computer device 1001 can operate in a networked environment using logical connections to one or more remote computer devices 1014a, 1014b, 1014c. The remote computer devices 1014a, 1014b, 1014c can be, for example, personal computers, computing stations (such as workstations), portable computers (e.g., laptops, mobile phones, tablet devices), smart devices (e.g., smartphones, smartwatches, activity monitors, smart apparel, smart accessories), security and / or surveillance devices, servers, routers, network computers, peer devices, edge devices, or other common network nodes. The logical connections between the computer device 1001 and the remote computer devices 1014a, 1014b, 1014c can be made using a network 1015 such as a local area network (LAN) and / or a general-purpose wide area network (WAN). Such network connections can be through a network adapter 1008. The network adapter 1008 can be implemented in both wired and wireless environments. Such network environments are conventional in homes, offices, enterprise-wide computer networks, intranets, and the Internet. It is contemplated that the remote computer devices 1014a, 1014b, 1014c may optionally have some or all of the components disclosed as being part of the computer device 1001.
[0143] Application programs such as operating system 1005 and other executable program components are shown herein as individual blocks, but such programs and components can exist at various times in different storage components of computer device 1001 and be executed by one or more processing units 1003 of computer device 1001, which is recognized. The implementation of electrode data processing software 1006 may be stored on or sent across a form of computer-readable medium. Any of the disclosed methods may also be implemented by processor-executable instructions embodied on a computer-readable medium.
[0144] Exemplary aspects In view of the products, systems, methods, and variations thereof described herein, specific, more particularly described aspects of the invention are described below herein. However, these specifically proposed aspects should not be construed as having a limiting effect on any different claims that include different teachings or more general teachings described herein, or as being limited in any way other than the literal meaning of the words used herein.
[0145] Aspect 1A: At least one enclosure comprising a floor defining a floor area having a major dimension, a cover having a bottom surface, the distance between the bottom surface of the cover and the floor defining a cage height, and at least one side wall extending between the floor and the cover, wherein the ratio of the cage height to the major dimension of the floor area of each enclosure of the at least one enclosure is at least 0.70.
[0146] Aspect 2A: The cage assembly of Aspect 1A, wherein the at least one enclosure comprises a first enclosure and a second enclosure.
[0147] Aspect 3A: The cage assembly of Aspect 1A, wherein at least one enclosure consists of a first enclosure and a second enclosure.
[0148] Aspect 4A: The cage assembly of Aspect 2A or Aspect 3A, wherein the first enclosure and the second enclosure share a common side wall that separates the floor region of the first enclosure from the floor region of the second enclosure.
[0149] Aspect 5A: The cage assembly of Aspect 4A, wherein the common side wall defines at least one opening between the first enclosure and the second enclosure.
[0150] Aspect 6A: The cage assembly of Aspect 5A, wherein each of the first enclosure and the second enclosure includes a respective shelter sub-assembly that extends inwardly from the common side wall within the enclosure, and the shelter sub-assembly at least partially surrounds the opening within the common side wall.
[0151] Aspect 7A: The cage assembly of any one of Aspect 1A to Aspect 6A, wherein the floor of each enclosure defines a corner, and each corner of the floor of the enclosure has a radius of at least 17 mm.
[0152] Aspect 8A: The cage assembly of any one of Aspect 1A to Aspect 7A, wherein the major dimension of the floor region of each enclosure is 250 mm or less.
[0153] Aspect 9A: The cage assembly of any one of Aspect 2A to Aspect 8A, wherein the floor of the first enclosure and the floor of the second enclosure are integrally constructed.
[0154] Aspect 10A: The cage assembly of any one of Aspect 2A to Aspect 9A, wherein the cover of the first enclosure and the cover of the second enclosure are integrally constructed as a cover assembly.
[0155] Aspect 11A: The cage assembly of Aspect 10A, wherein the cover assembly includes a first opening and a second opening that respectively provide communication with the first enclosure and the second enclosure, the first opening being configured to provide communication to a first cable and the second opening being configured to provide communication to a second cable.
[0156] Aspect 12A: The cage assembly of Aspect 11A, wherein the cover assembly includes a first swivel assembly and a second swivel assembly disposed in a covering relationship with the first opening and the second opening respectively, the first swivel assembly being configured to receive a proximal portion of the first cable and the second swivel assembly being configured to receive a proximal portion of the second cable.
[0157] Aspect 13A: The cage assembly of Aspect 12A, wherein each of the first swivel assembly and the second swivel assembly includes a motor housing and a motor received within the motor housing, the motor of the first swivel assembly being configured to be coupled to the first cable to allow adjustment of the first cable and the motor of the second swivel assembly being configured to be coupled to the second cable to allow adjustment of the second cable.
[0158] Aspect 14A: The cage assembly of Aspect 1A, wherein at least one enclosure includes the first enclosure, the cover includes a swivel assembly disposed in a covering relationship with the first enclosure, and the cover further includes an opening configured to provide communication between the cable and the swivel assembly.
[0159] Aspect 15A: The cage assembly of Aspect 14A, wherein the swivel assembly includes a motor configured to be coupled to a proximal portion of the cable to allow adjustment of movement of the cable.
[0160] Aspect 16A: The cage assembly of any one of Aspects 4A to 13A, wherein at least one side wall of each of the first enclosure and the second enclosure further includes a front wall, a rear wall, and a transverse wall extending between the front wall and the rear wall and opposite a common side wall.
[0161] Aspect 17A: The cage assembly of Aspect 16A, wherein at least a portion of the front wall of the first enclosure and at least a portion of the front wall of the second enclosure are integrally constructed.
[0162] Aspect 18A: The cage assembly of Aspect 16A or Aspect 17A, wherein the rear wall of the first enclosure and the rear wall of the second enclosure are integrally constructed.
[0163] Aspect 19A: The front walls of the first enclosure and the second enclosure include a base portion fixed to the lateral walls of the first enclosure and the second enclosure, and a door pivotally connected to the base portion. The door is configured for movement between a closed position in which it cooperates with the front walls, lateral walls, rear walls, and cover of the first enclosure and the second enclosure to enclose the internal space within the cage assembly, and an open position in which the internal space of the cage assembly is accessible. The cage assembly of Aspect 17A further includes the door.
[0164] Aspect 20A: The cage assembly of Aspect 19A, wherein the door is pivotally connected to the base portion by a hinge connection.
[0165] Aspect 21A: The cage assembly of Aspect 19A or Aspect 20A further includes a latch mechanically connected to the door. The latch is movable between and around a latched position that prevents pivotal movement of the door when the door is in the closed position and an unlatched position that allows pivotal movement of the door relative to the base portion.
[0166] Aspect 22A: The cage assembly of any one of Aspects 1A to 21A, wherein the floor, cover, and at least one side wall of each enclosure include polycarbonate.
[0167] Aspect 23A: The cage assembly of any one of Aspects 1A to 22A, wherein at least a portion of the cover and at least one side wall of each enclosure is transparent.
[0168] Aspect 24A: A cage assembly of any one of Aspects 1A to 23A, wherein the cover defines an opening configured to receive an electrical cord.
[0169] Aspect 25A: A cage assembly of any one of Aspects 1A to 24A, wherein the floor of each enclosure is provided with padding.
[0170] Aspect 26A: A cage assembly of any one of Aspects 1A to 25A, wherein at least one side wall of each enclosure is provided with a ventilation opening.
[0171] Aspect 27A: The cage assembly of Aspect 26A, further comprising at least one filter configured to cover at least one ventilation opening of at least one side wall.
[0172] Aspect 28A: The cage assembly of Aspect 27A, further comprising a frame configured to mechanically connect the filter to at least one side wall.
[0173] Aspect 29A: The cage assembly of Aspect 27A, wherein the cage assembly is sealed such that all or substantially all ventilation to each enclosure passes through at least one filter before entering the ventilation opening.
[0174] Aspect 30A: A cage assembly of any one of Aspects 1A to 29A, wherein the side walls of each enclosure have equal lengths.
[0175] Aspect 31A: A cage assembly of any one of Aspects 1A to 30A, wherein the ratio of the cage height to the major dimension of the floor area of each enclosure of at least one enclosure is at least 1.0.
[0176] Aspect 32A: A cage assembly comprising at least one enclosure having a floor defining a floor area with a major dimension, a cover having a bottom surface, wherein the distance between the bottom surface of the cover and the floor defines a cage height, and at least one side wall extending between the floor and the cover, wherein the height h is a function of the major dimension Y of the floor according to the formula: h≧(Y2 - 6400) / 320, where h and Y are in millimeters.
[0177] Aspect 33A: A method comprising the steps of placing an animal subject in each enclosure of a cage assembly of any one of the previous aspects, and connecting a distal end of a cable to the animal subject within each enclosure, wherein at least 90% of the floor area of the enclosure is accessible by the animal subject.
[0178] Aspect 34A: The method of aspect 33A, further comprising the step of connecting a proximal end of each cable to a swivel assembly, each cable having an operating portion with an operating length, and each operating length being selected such that an animal subject cannot be present at a position within each enclosure where the distance between the operating portions of the cables is within a threshold distance of the floor.
[0179] Aspect 35A: The method of aspect 33A or aspect 34A, wherein the animal subject is a mouse.
[0180] Aspect 36A: The method of aspect 35A, wherein the cage assembly comprises a first enclosure and a second enclosure, a first mouse being placed in the first enclosure and a second mouse being placed in the second enclosure.
[0181] Aspect 37A: The method of aspect 36A, wherein the first enclosure and the second enclosure share a common side wall separating the floor area of the first enclosure from the floor area of the second enclosure, the common side wall defining at least one opening between the first enclosure and the second enclosure, the at least one opening allowing communication between the first mouse and the second mouse.
[0182] Aspect 38A: A method according to any one of Aspects 33A to 37A, wherein the electrical cord is connected to an animal subject through a treatment assembly comprising a transducer array.
[0183] Aspect 39A: The method of Aspect 38A, further comprising the step of using the electrical cord and the treatment assembly to apply an electric field to an animal subject within at least one enclosure.
[0184] Aspect 40A: The method of Aspect 39A, wherein the animal subject has a tumor and the electric field is a tumor treatment electric field.
[0185] Aspect 41A: A method according to any one of Aspects 33A to 40A, further comprising the step of inspecting or accessing the animal subject through the cage assembly without removing the animal subject from the cage assembly.
[0186] Aspect 42A: A method according to any one of Aspects 33A to 41A, further comprising the step of removing the animal subject from the cage assembly and the step of autoclaving the floor, cover, and at least one side wall of each enclosure.
[0187] Aspect 1B: A treatment assembly comprising an inner layer having an inner surface and an outer surface, the inner layer defining a plurality of openings extending therethrough; a plurality of plates, at least a portion of each of which is received within a respective one of the plurality of openings of the inner layer; a treatment circuit comprising a cable having a plurality of electrical leads and a plurality of electrical lead ends, each of the plurality of electrical leads being electrically connected to a respective one of the plurality of electrical lead ends; and a cover layer 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 respective ones of the plurality of plates to define a plurality of electrodes, and each of the plurality of electrodes comprises a respective lead end and a respective plate.
[0188] Aspect 2B: The treatment assembly of Aspect 1B, wherein at least one of the plurality of plates comprises a ceramic plate.
[0189] Aspect 3B: The treatment assembly of Aspect 1B, wherein at least one of the plurality of plates comprises a glass plate.
[0190] Aspect 4B: The treatment assembly according to any one of Aspects 1B to 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.
[0191] Aspect 5B: The treatment assembly according to any one of Aspects 1B to 4B, wherein the plurality of electrodes of the treatment circuit each have an upper surface, and the cover layer extends across the upper surfaces of the electrodes of the cable.
[0192] Aspect 6B: The treatment assembly according to any one of Aspects 1B to 5B, wherein each of the plurality of plates has an upper surface opposite to the lower surface, and the treatment assembly further comprises a layer of hydrogel on the lower surface of each of the plurality of plates.
[0193] Aspect 7B: The treatment assembly according to any one of Aspects 1B to 6B, wherein the treatment circuit further comprises at least one temperature sensor.
[0194] Aspect 8B: The treatment assembly according to any one of Aspects 1B to 7B, wherein the inner layer and the cover layer cooperate to define a hole through the treatment assembly, and the hole is configured to receive a subcutaneous tumor therethrough.
[0195] Aspect 9B: The treatment assembly of Aspect 8B, further comprising a cap attached to the cover layer, the cap defining therein a receiving portion extending through the hole and configured to receive a subcutaneous tumor.
[0196] Aspect 10B: The treatment assembly of Aspect 8B or Aspect 9B, wherein the plurality of plates are disposed radially outward of the diameter of the hole defined through the treatment assembly.
[0197] Aspect 11B: The treatment assembly of Aspect 9B or Aspect 10B, wherein the cap has a periphery, and the treatment assembly further comprises an adhesive ring that covers the periphery and secures the cap to the cover layer.
[0198] Aspect 12B: The treatment assembly of any one of Aspects 1B to 11B, wherein the treatment assembly has a longitudinal dimension in a pre-use configuration, the cover layer includes a biocompatible non-woven adhesive, and the non-woven adhesive is elastic in the longitudinal dimension.
[0199] Aspect 13B: The treatment assembly of Aspect 12B, wherein in a use configuration, the cable extends perpendicular or substantially perpendicular to the longitudinal dimension.
[0200] Aspect 14B: The treatment assembly of any one of Aspects 1B to 13B, wherein the inner layer comprises a biocompatible and breathable polyurethane that adheres to the inner surface of the inner layer.
[0201] Aspect 15B: The treatment assembly of Aspect 14B, wherein the cover layer has an inner surface that includes a biocompatible non-woven adhesive.
[0202] Aspect 16B: The treatment assembly of any one of Aspects 1B to 15B, wherein the plurality of electrodes comprises a plurality of electric field generating electrodes, and the plurality of electric field generating electrodes are configured to transmit an electric field through corresponding plates of the plurality of plates.
[0203] Aspect 17B: The treatment assembly of Aspect 16B, wherein the treatment circuit further comprises a plurality of thermistors.
[0204] Aspect 18B: The treatment assembly of Aspect 17B, wherein each electrode of the plurality of electrodes and each thermistor of the plurality of thermistors communicate with each plate of the plurality of plates.
[0205] Aspect 19B: The treatment assembly of any one of Aspects 1B to 18B, wherein the treatment assembly has a weight of less than 2.5 grams.
[0206] Aspect 20B: Any one of the treatment assemblies of Aspect 1B to Aspect 19B, having flexibility that only matches circumferentially on a part of the torso of the animal subject.
[0207] Aspect 21B: Any one of the treatment assemblies of Aspect 1B to Aspect 20B, wherein the cable comprises end connectors disposed at opposite ends of the cable of the plurality of electrodes, and the end connectors are configured to allow connection of the cable to an electrical signal generating device.
[0208] Aspect 22B: The treatment assembly of Aspect 14B, further comprising a release layer that contacts a biocompatible and breathable polyurethane that adheres to the inner surface of the inner layer.
[0209] Aspect 23B: The treatment assembly of Aspect 22B, wherein the release layer has a shape that is complementary to the shape of the cover layer.
[0210] Aspect 24B: Any one of the treatment assemblies of Aspect 1B to Aspect 23B, wherein the cover layer defines at least one tab portion that extends beyond the inner layer.
[0211] 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.
[0212] Aspect 26B: Any one of the treatment assemblies of Aspect 1B to Aspect 7B or Aspect 12B to Aspect 25B, wherein the plurality of openings comprises a plurality of openings spaced apart in the longitudinal direction.
[0213] Aspect 27B: Any one of the treatment assemblies of Aspect 1B to Aspect 26B, wherein the treatment circuit and the cable are integrally constructed as a flexible printed circuit board.
[0214] Aspect 28B: A method of making a treatment assembly according to any one of Aspects 1B to 27B, including the steps of disposing a plurality of plates inside the inner layer of the treatment assembly within each opening, disposing each electrode of the plurality of electrodes of the treatment circuit in contact with a plate of the plurality of plates, and attaching a cover layer to the outer surface of the inner layer, wherein the cover layer covers the plurality of electrodes of the treatment circuit.
[0215] Aspect 29B: The method of Aspect 28B, further including the step of applying a layer of hydrogel to the lower surface of each plate of the plurality of plates.
[0216] Aspect 30B: The method of Aspect 29B, wherein the lower surfaces of at least two plates of the plurality of plates share a layer of hydrogel.
[0217] Aspect 31B: A method including the steps of electrically connecting at least a portion of the electrodes of a treatment assembly according to any one of Aspects 1B to 27B to an electrical signal generating device, attaching the treatment assembly to an animal subject having a tumor, wherein the plate of the treatment assembly surrounds at least a portion of the tumor, using the electrical signal generating device to generate an electrical signal, and using the at least a portion of the electrodes of the treatment assembly to generate an electric field from the electrical signal through the corresponding plate of the plurality of plates.
[0218] Aspect 32B: The method of Aspect 31B, wherein the tumor is an organ tumor, and 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 subject to surround the organ tumor.
[0219] Aspect 33B: The method of Aspect 31B, wherein the tumor is a subcutaneous tumor, and the plurality of openings are radially spaced from holes extending through the treatment assembly, and the holes receive at least a portion of the subcutaneous tumor.
[0220] Aspect 34B: The method of Aspect 33B, further comprising the step of placing a cap over the subcutaneous tumor and the step of fixing the cap to the cover layer of the treatment assembly.
[0221] Aspect 35B: The step of using an electrical signal generating device to generate an electrical signal includes continuously generating a first electrical signal and a second electrical signal. To generate an electric field from the electrical signal, the step of using at least a portion of the electrodes of the treatment assembly includes using the first electrode and the second electrode to generate a first electric field across the tumor from the first electrical signal, and using the third electrode and the fourth electrode to generate a second electric field across the tumor from the second electrical signal. The method according to any one of Aspects 31B to 34B.
[0222] Aspect 36B: The method of Aspect 35B, wherein the first electric field and the second electric field each have an axis of propagation, and the axis of propagation of the first electric field intersects the axis of propagation of the second electric field.
[0223] Aspect 37B: The step of using an electrical signal generating device to generate an electric field includes generating an electric field at a frequency between 50 kHz and 500 kHz. The method according to any one of Aspects 28B to 36B.
[0224] Aspect 38B: The animal subject is a member of the experimental group. The method includes electrically connecting at least a portion of the electrodes of a control heating device according to any one of Aspects 39B to 42B to the electrical signal generating device, and attaching the control heating device to a second animal subject having a tumor, wherein the second animal subject is a member of the control group and the heater of the second treatment assembly surrounds at least a portion of the tumor. The method further includes using the electrical signal generating device to generate heat through the heater of the control heating device, and at least a portion of the electrodes of the second treatment assembly transferring heat through corresponding plates of the plurality of plates, and the heat generated by the control heating device mimicking the heat generated by the first treatment assembly during the delivery of the electric field. The method according to any one of Aspects 31B to 37B.
[0225] Aspect 39B: A control heating device comprising a plurality of zones arranged in a spaced-apart configuration that conforms to the configuration of a plurality of electrodes of a treatment assembly as in any one of Aspect 1B to Aspect 27B, at least one heater disposed in each zone of the plurality of zones, at least one temperature sensor, and a cable in communication with at least one heater and at least one temperature sensor of the circuit.
[0226] Aspect 40B: The control heating device of Aspect 39B, wherein the at least one temperature sensor comprises a plurality of temperature sensors, and each temperature sensor of the plurality of temperature sensors is disposed in each zone of the plurality of zones.
[0227] Aspect 41B: The control heating device of Aspect 39B or Aspect 40B, wherein the circuit and the cable are integrally constructed as a flexible printed circuit board.
[0228] Aspect 42B: The control heating device of any one of Aspect 39B to Aspect 41B, further comprising an inner layer having an upper surface and comprising a plurality of openings, wherein each zone is disposed within an opening of the plurality of openings, and a cover layer extending across the upper surface of the inner layer.
[0229] Aspect 43B: The treatment assembly of any one of Aspect 1B to Aspect 27B, wherein the plurality of electrodes comprises a plurality of head electrodes configured to be disposed on the head of a test subject and a plurality of body electrodes configured to be disposed on the torso of the test subject.
[0230] Aspect 44B: The treatment assembly of Aspect 43B, wherein the treatment circuit comprises a meandering portion extending from the plurality of body electrodes to the plurality of head electrodes.
[0231] Aspect 45B: The plurality of head electrodes includes a first group of electrodes arranged on a first side with respect to the midplane, and a second plurality of electrodes arranged on a second side opposite to the first side with respect to the midplane. The plurality of torso electrodes includes at least a first torso electrode arranged on the first side and at least a second torso electrode arranged on the second side. The treatment assembly of Aspect 43B or Aspect 44B.
[0232] Aspect 1C: A swivel assembly having a longitudinal axis, an upper portion, and a lower portion rotatably connected to the upper portion, the lower portion having a connector configured to firmly engage with a cable, the lower portion configured to remain in electrical communication with the upper portion when rotating with respect to the upper portion, a motor positioned between the upper portion and the lower portion and configured to selectively rotate the lower portion, a sensor configured to detect torsion in the cable, and a control device in communication with the sensor and the motor. When the control device receives a signal from the sensor indicating a threshold torsion in the cable, the control device is configured to rotate the motor in a direction corresponding to the direction of torsion in the cable. The swivel assembly.
[0233] Aspect 2C: The connector of the lower portion is an electrical connector, and the electrical connector is configured to firmly engage with an electrical cable. The swivel assembly of Aspect 1C.
[0234] Aspect 3C: The electrical connector is configured for electrical communication with an electrical signal generating device and is further configured to permit electrical communication between the electrical signal generating device and the electrical cable. The swivel assembly of Aspect 2C.
[0235] Aspect 4C: The control device is configured to rotate the motor in a direction corresponding to the direction of torsion of the cable until it receives a signal from the sensor indicating that the torsion in the cable has dropped below a second threshold. The swivel assembly of any one of Aspects 1C to 3C.
[0236] Aspect 5C: The swivel assembly further includes a mounting assembly attached to the upper part of the swivel part with respect to the longitudinal axis, and the lower part of the swivel part is rotatably connected to the mounting assembly via the upper part of the swivel part, which is any one of the swivel assemblies from Aspect 1C to Aspect 4C.
[0237] Aspect 6C: The swivel assembly of Aspect 5C, wherein the mounting assembly is configured to be fixed to the upper surface of the cage.
[0238] Aspect 7C: The swivel assembly of Aspect 5C or Aspect 6C, wherein the mounting assembly defines an opening communicating with the cable outlet.
[0239] Aspect 8C: The lower part is under the motor and includes a base plate engaged with the motor, and the motor applies a rotational force to the lower part through the base plate, which is any one of the swivel assemblies from Aspect 1C to Aspect 7C.
[0240] Aspect 9C: The upper part includes a support plate covering the motor, which is any one of the swivel assemblies from Aspect 1C to Aspect 8C.
[0241] Aspect 10C: The upper part further includes a vibration damping plate covering the motor, which is any one of the swivel assemblies from Aspect 1C to Aspect 9C.
[0242] Aspect 11C: The control device is configured to detect abnormal rotation of the swivel assembly, and the abnormal rotation is detected by at least one of (1) one or more signals from a sensor indicating the frequency of change in the rotation direction exceeding a frequency threshold, or (2) one or more signals from a sensor indicating continuous rotation in a single rotation direction exceeding a time threshold, which is any one of the swivel assemblies from Aspect 1C to Aspect 10C.
[0243] Aspect 12C: The control device of the swivel assembly of Aspect 11C, which is configured to receive a user input to determine at least one of the frequency threshold or the time threshold.
[0244] Aspect 13C: The swiveling assembly of Aspect 11C or Aspect 12C, further comprising a warning indicator, wherein the control device is configured to activate the warning indicator when an abnormal rotation is detected.
[0245] Aspect 14C: The swiveling assembly of Aspect 13C, wherein the warning indicator comprises at least one of a visible indicator or an audible indicator.
[0246] Aspect 15C: The sensor is a pivot body pivotally connected to a lower part of the swivel part around a pivot axis and configured to be connected to a cable so that a twist of the cable applies torque to the pivot body that causes pivoting of the pivot body relative to the lower part of the swivel part. The pivot body comprises a radially extending surface extending radially outward with respect to the pivot axis, a spring configured to bias the pivot body to a neutral position relative to the lower part of the swivel part, and first and second electro-optical sensors spaced radially from the pivot axis of the pivot body at respective angular positions of the pivot body. When the pivot body pivots from the neutral position by a first threshold angular distance in a first direction, the radially extending surface of the pivot body is configured to cause a change in state in the first electro-optical sensor. When the pivot body pivots from the neutral position by a second threshold angular distance in a second, opposite direction, the radially extending surface of the pivot body is configured to cause a change in state in the second electro-optical sensor. The swiveling assembly according to any one of Aspects 1C to 14C.
[0247] Aspect 16C: The swiveling assembly of Aspect 15C, further comprising a first part rotatably fixed to a lower part of the swivel part, a second part pivotable with the pivot body, and a printed circuit board having at least one notch such that the printed circuit board comprises a patterned part capable of pivoting the first part relative to the second part.
[0248] Aspect 17C: Each of the first and second electro-optical sensors includes a light source, a photodetector, and an optical path between the light source and the photodetector. The radially extending surface of the pivoting body is configured to block the respective optical paths of each of the first electro-optical sensor and the second electro-optical sensor when the pivoting body is in the neutral position. A change in state in the first electro-optical sensor due to the pivoting body pivoting from the neutral position in a first direction by a first threshold angular distance includes the first electro-optical sensor no longer detecting the radially extending surface that blocks the optical path of the first electro-optical sensor. A pivoting assembly as in Aspect 15C or Aspect 16C.
[0249] Aspect 18C: A pivoting assembly as in Aspect 17C, wherein the radially extending surface of the pivoting body includes a protrusion.
[0250] Aspect 19C: A pivoting assembly according to any one of Aspects 1C to 18C, wherein the motor is a brushless gimbal motor.
[0251] Aspect 20C: A pivoting assembly according to any one of Aspects 1C to 19C, further comprising a cable having a proximal end portion fixed to a connector and an opposite distal end, the cable being configured to move in response to the application of a force to the distal end portion of the cable.
[0252] Aspect 21C: A pivoting assembly according to any one of Aspects 1C to 20C, further comprising a slip ring configured to provide electrical communication between an upper portion and a lower portion when the lower portion rotates relative to the upper portion.
[0253] Aspect 22C: A pivoting assembly according to any one of Aspects 1C to 21C, wherein the cable is part of a flexible printed circuit board.
[0254] Aspect 23C: A method including the step of fixing a proximal end portion of a cable to a connector of a pivoting assembly according to any one of Aspects 1C to 22C, and the step of using a control device to rotate a motor in a direction responsive to a first direction of twist in the cable in a first direction.
[0255] Aspect 24C: The method of Aspect 23C, wherein the cable is an electrical cable and the cable has a distal end portion that is electrically connected to the electrode array.
[0256] Aspect 25C: The method of Aspect 24C, wherein the electrode array is connected to an animal subject.
[0257] Aspect 26C: The method of Aspect 25C, wherein the animal subject is placed in a cage and the swivel assembly is fixed to the cage.
[0258] Aspect 27C: The method according to any one of Aspects 23C to 26C, further comprising the step of using a control device to determine abnormal rotation based on at least one of (1) one or more signals from a sensor indicating the frequency of change in the rotational direction exceeding a frequency threshold, or (2) one or more signals from a sensor indicating continuous rotation in a single rotational direction exceeding a time threshold.
[0259] Aspect 28C: A system comprising a computer device comprising a swivel assembly as in any one of Aspects 1C to 22C and a storage device communicating with at least one processing device, the storage device storing at least one measurement criterion selected from the group consisting of the number of rotations, the number of rotations in a first selected period, the frequency of motor operation, the frequency of motor operation in a second selected period, the number of motor operations including a change in direction, the number of motor operations in a second selected period including a change in direction, the period of constant operation, and the log of motor operations and the corresponding times of motor operations, the system including instructions for causing at least one processing device to perform a method including the step of storing the at least one measurement criterion in the storage device when the method is executed.
[0260] Aspect 29C: The swivel assembly of Aspect 28C, the system including instructions for causing at least one processing device to perform a method further comprising the step of generating a log report including at least one measurement criterion when the method is executed.
[0261] Aspect 30C: The swivel assembly of Aspect 29C, wherein the log report further includes at least one comparison of at least one measurement criterion and the average of at least one measurement criterion over a specific time period.
[0262] Aspect 1D: A system comprising any one of the cage assemblies of Aspects 1A to 32A and any one of the swivel assemblies of Aspects 1C to 22C.
[0263] Aspect 2D: The system of Aspect 1D, further comprising any one of the treatment assemblies of Aspects 1B to 27B.
[0264] Aspect 3D: The system of Aspect 1D, further comprising any one of the control heating devices of Aspects 39B to 42B.
[0265] Aspect 4D: A method of using any one of the systems of Aspects 1D to 3D.
[0266] The foregoing invention has been described in some detail by way of illustration and example for the purpose of clarity of understanding, but certain changes and improvements may be made within the scope of the appended claims.
Description of the Reference Numerals
[0267] 1 Inner adherable layer 2 Hydrogel part 3 Ceramic plate 4 Inner adhesion patch 5 Flexible circuit board 6 Head-wearable layer 7 Outer adherable layer 8 End of the circuit board 9a Head covering part 9b Trunk covering part 10 System 12 Test subject, signal generator 16 Angle 18 TTField generating device 20 Second cable 60 Axis of the first propagation 100 Cage assembly 102 Main body 104 Bed 108 Side wall 108A Front side wall 108B Rear side wall 108C Side wall 110 Corner 112 Door 114 Hinge 120 Cover 122 Latching part 124 Hinge 126 Latching part 128 Hinge 130 Opening 132 Filter 134 Frame 136 Nut 138 Bolt 140 Partition 142 First enclosure 144 Second enclosure 146 Opening 150 Shelter sub - assembly 178 Cover assembly 180 Swivel part housing 182 Side wall 184 Inner circumferential direction insert 186 Upper cover 200, 200', 200" TTField treatment assembly 201 Longitudinal dimension, longitudinal axis 202, 202' Circuit board 204, 204' Cable 205 Electrical lead wire 206, 206' Connector end 208, 208' Lead wire end 210, 210' Plate 212, 212' Inner layer 214 Outer surface 216 Inner surface 218, 218' Opening 220 Upper side 222 Lower side 224, 224' Hydrogel layer 230, 230' Cover layer 232 tab portion 250, 250' release layer 252, 252' tab 260 temperature sensor 270' through-hole 272' cap 274' receiving part 276' periphery, flange 278' adhesive ring 300 swivel assembly, swivel part 302 damping plate 304 motor mounting plate 306 screw 314 base 316 screw, bearing housing, pivoting body 318 standoff 320 dependent tab 322 circuit assembly 324 printed circuit board 326 input / output connector 328 patterned part 330 base part 332 cable connector end 334 sensor connector part 340 bearing 342 pivoting body 344 slot 346 tab 350 standoff 352 protrusion 354 neutral position 356 sensor 356A first sensor 356B second optical sensor 358 sensor mounting part 359 circuit board, PCB 364 limiting part 380 connector 400, 400' control heater treatment assembly 402, 402' flexible circuit board 404 cable 406, 406' connector end 410 hydrogel, zone 412 Board, Resistance Heater 414, 414' Temperature Sensor 416 Hydrogel 420, 420' Inner Layer 430, 430' Cover Layer, Cover Liner 440, 440' Release Liner 450' Cap 500 Ring Body 502 Protrusion 504 Hole 506 First End 508 Second End 510 Inner Surface 512 Outer Surface 602, 602a, 602b Electrode 604 Electrode 606 Median Plane 700 Alternating Shape Portion 1000 System 1001 Computer Device 1002 Human Machine Interface 1003 Processing Device 1004 Mass Storage Device 1005 Operating System 1006 TTField Providing Software, Electrode Data Processing Software 1007 Temperature Data 1008 Network Adapter 1009 Display Adapter 1010 Input / Output Interface 1011 Display Device, Display Unit 1012 System Memory Device 1013 Bus 1014a, 1014b, 1014c Computer Device 1015 Network D Distance d Interval h Cage Height R1 Length of Enclosure R2 Width of Enclosure t Threshold Distance of Cage Floor
Claims
1. A floor defining a floor area having main dimensions, A cover having a bottom surface, wherein the distance between the bottom surface of the cover and the floor defines a cage height, At least one side wall extending between the floor and the cover, and At least one enclosure each having, The ratio of the cage height to the main dimension of the floor area of each of the at least one enclosure is at least 0.70, The at least one enclosure comprises a first enclosure and a second enclosure, and the first enclosure and the second enclosure share a common side wall separating the floor area of the first enclosure from the floor area of the second enclosure, and the common side wall defines at least one opening between the first enclosure and the second enclosure, Each of the first enclosure and the second enclosure comprises a respective shelter sub-assembly extending inwards from the common side wall within the enclosure, and the shelter sub-assembly is a cage assembly that at least partially surrounds the opening within the common side wall.
2. The at least one enclosure consists of a first enclosure and a second enclosure, the cage assembly according to claim 1.
3. The floor of each enclosure defines a corner, and each corner of the floor of the enclosure has a radius of at least 17 mm, the cage assembly according to claim 1.
4. The main dimension of the floor area of each enclosure is 250 mm or less, the cage assembly according to claim 1.
5. The floor of the first enclosure and the floor of the second enclosure are integrally constructed, the cage assembly according to claim 1.
6. The cover of the first enclosure and the cover of the second enclosure are integrally constructed as a cover assembly, the cage assembly according to claim 1.
7. The cover assembly includes a first opening and a second opening that respectively provide communication with the first enclosure and the second enclosure, the first opening being configured to provide communication to a first cable, and the second opening being configured to provide communication to a second cable, the cage assembly according to claim 6.
8. The cover assembly includes a first swivel assembly and a second swivel assembly respectively disposed in a covering relationship with the first opening and the second opening, the first swivel assembly being configured to receive a proximal portion of the first cable, and the second swivel assembly being configured to receive a proximal portion of the second cable, the cage assembly according to claim 7.
9. Each of the first swivel assembly and the second swivel assembly includes a motor housing and a motor received within the motor housing, the motor of the first swivel assembly being configured to be coupled to the first cable to allow adjustment of the first cable, and the motor of the second swivel assembly being configured to be coupled to the second cable to allow adjustment of the second cable, the cage assembly according to claim 8.
10. The at least one enclosure includes a first enclosure, the cover includes a swivel assembly disposed in a covering relationship with the first enclosure, the cover further includes an opening configured to provide communication with the first enclosure, and the opening is configured to provide communication between the cable and the swivel assembly, the cage assembly according to claim 9.
11. The swivel assembly includes a motor, and the motor is configured to be coupled to a proximal portion of the cable to allow adjustment of movement of the cable, the cage assembly according to claim 10.
12. Each of the at least one side wall of the first enclosure and the second enclosure a front side wall, a rear side wall, A transverse side wall that faces the common side wall and extends between the front side wall and the rear side wall, and The cage assembly according to claim 1, further comprising.
13. At least a part of the front side wall of the first enclosure and at least a part of the front side wall of the second enclosure are integrally constructed, and the cage assembly according to claim 12.
14. The rear side wall of the first enclosure and the rear side wall of the second enclosure are integrally constructed, and the cage assembly according to claim 12.
15. The front side wall of the first enclosure and the front side wall of the second enclosure are A base portion fixed to the transverse side wall of the first enclosure and the transverse side wall of the second enclosure, and A door pivotally connected to the base portion, and the door is configured to cooperate with the front side wall, the transverse side wall, the rear side wall, and the cover of the first enclosure and the second enclosure to surround the internal space in the cage assembly. A door configured for movement between and around a closed position and an open position where the internal space of the cage assembly is accessible. The cage assembly according to claim 13, further comprising.
16. The door is pivotally connected to the base portion by a hinge connection, and the cage assembly according to claim 15.
17. Further comprising a latch mechanically connected to the door, the latch being movable between and around a latching position that prevents pivotal movement of the door when the door is in the closed position and a latching release position that allows pivotal movement of the door relative to the base portion. The cage assembly according to claim 15.
18. The floor, the cover, and the at least one side wall of each enclosure include polycarbonate, and the cage assembly according to claim 1.
19. The cage assembly according to claim 1, wherein at least a portion of the cover and the at least one side wall of each enclosure is transparent.
20. The cage assembly according to claim 1, wherein the cover defines an opening configured to receive a cable.
21. The cage assembly according to claim 1, wherein the floor of each enclosure comprises a filler.
22. The cage assembly according to claim 1, wherein at least one side wall of each enclosure comprises a ventilation opening.
23. The cage assembly according to claim 22, further comprising at least one filter configured to cover at least one ventilation opening of the at least one side wall.
24. The cage assembly according to claim 23, further comprising a frame configured to mechanically connect the filter to the at least one side wall.
25. The cage assembly according to claim 23, wherein the cage assembly is sealed such that all or substantially all ventilation to each enclosure proceeds through the at least one filter before entering the ventilation opening.
26. The cage assembly according to claim 1 or 2, wherein the side walls of each enclosure have equal lengths.
27. The cage assembly according to claim 1, wherein the ratio of the cage height to the major dimension of the floor region of each enclosure of the at least one enclosure is at least 1.
0.
28. The cage height h is a function of the major dimension Y of the floor region according to the formula h≧(Y 2 -6400) / 320, where Y is the major dimension of the floor region, and h and Y are in millimeters. The cage assembly according to claim 1.
29. Placing an animal subject in each enclosure of the cage assembly according to any one of claims 1 to 28; Connecting the distal end of the cable to the animal subject within each enclosure; comprising: A method, wherein at least 90% of the floor area of the enclosure is accessible by the animal subject. **Claim 30** Further comprising connecting the proximal end of each cable to a swivel assembly; Each cable has an operating portion having an operating length, and each operating length is such that the distance between the operating portions of the cables is within a threshold distance of the floor in each enclosure where each animal subject cannot be present. The method according to claim 29, wherein the method is selected. **Claim 31** The method according to claim 29, wherein the animal subject is a mouse. **Claim 32** The cage assembly comprises a first enclosure and a second enclosure, a first mouse is placed in the first enclosure, and a second mouse is placed in the second enclosure. The method according to claim 31. **Claim 33** The first enclosure and the second enclosure share a common sidewall that separates the floor area of the first enclosure from the floor area of the second enclosure, and the common sidewall defines at least one opening between the first enclosure and the second enclosure. The method according to claim 32, wherein the at least one opening permits communication between the first mouse and the second mouse. **Claim 34** The method according to claim 29 when dependent on claim 20, wherein the cable is connected to the animal subject through a treatment assembly comprising a transducer array. **Claim 35** Further comprising using the cable and the treatment assembly to apply an electric field to the animal subject within the at least one enclosure. The method according to claim 34.
36. The method according to claim 35, wherein the animal subject has a tumor and the electric field is a tumor treatment electric field.
37. The method according to claim 29, further comprising the step of examining the animal subject or accessing the animal subject through the cage assembly without removing the animal subject from the cage assembly.
38. The step of removing the animal subject from the cage assembly, and the step of autoclaving the floor, the cover, and the at least one side wall of each enclosure, The method according to claim 29, further comprising.
Citation Information
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