GB2474640A - Metabolic Chamber - Google Patents

Abstract

A metabolic chamber including an animal compartment and a top cover 2, wherein the top cover contains at least one feeding station 6, 10 depending therefrom. The feed stations comprise hoppers 28, 30 surrounded by rotatable cylindrical covers 8, 12 to allow selective feeding. The hopper may be supplied with measurement means. The top cover attaches to the animal compartment in an air tight manner and a releasable locking arrangement is employed. A further lid (60, 62, fig 3) may be provided. An array of chambers is also claimed.

Description

Metabolic Chamber The present invention relates to a metabolic chamber, in particular to a metabolic chamber for use with rodent test subjects.

Metabolic chambers are used in animal trials to measure the effect of particular stimuli, e.g. drug substances, on the metabolism of animals, typically rodents such as mice or rats.

A metabolic chamber needs to provide an environment for the test subjects within which food and water intake can be measured, as well as respiration. Typically, metabolic chambers include an animal compartment, a food source, a water source and means to measure respiration of the test subjects. However, conventional chambers present problems for the user.

Test subjects are usually reared and held in a holding cage and then moved to the metabolic chamber where the environment is different to that to which they had become accustomed. This can lead to stress in the test subjects, which in turn can adversely affect the results of the experiment. In addition, it is often difficult for the experimenter to change the food and/or fluid in conventional chambers.

The present invention provides a metabolic chamber including an animal compartment and a top cover, wherein the top cover contains at least one feeding station depending therefrom.

The metabolic chamber may include a local controller which controls the functions of the chamber.

The local controller may also record data collected by one or more sensors carried by the chamber.

As the feeding station for the chamber is provided in the top cover, the animal compartment can be an animal compartment within which the test subjects have been reared or at least have had an opportunity to become accustomed to. Thus, the animal compartment can be a compartment to which the test subjects have been acclimatised.

Accordingly, the present invention provides a metabolic chamber which is adapted to be used with a standard animal compartment.

Known metabolic chambers require a very carefully controlled animal compartment to be used, which includes, for example, the use of specialist bedding materials or requires that no bedding materials are used. However, a standard animal compartment can be used with the present invention, as all of the essential components for monitoring the metabolism of the test subjects are housed in the top cover, which means that animal bedding and other features of standard animal compartments can be used, which helps to minimise stress experienced by the test subjects.

Moreover, as the feeding station is carried by the top cover, it can be accessed from above, without the need to remove the top cover from the animal compartment.

In an embodiment of the invention, the top cover has an open configuration, in which it is spaced from the animal compartment, and a closed configuration in which it forms a gas-tight seal with the animal compartment. Thus, the top cover may be hinged such that it is capable of being pivoted away from or towards the animal compartment or it may be spaced vertically from and substantially parallel to the animal compartment in the open configuration. In this embodiment, the top cover may include a gasket or seal located about its downwardly facing periphery, such that in use, the gasket or seal is trapped between the top cover and the animal compartment to provide the gas-tight seal.

In a further embodiment, the top cover includes a releasable lock adapted to releasably lock the top cover in the open configuration. This permits a user to access the animal compartment without the interference of the top cover or the risk of the top cover inadvertently falling onto or otherwise hitting the animal compartment. Additionally or alternatively, the top cover may include a releasable lock adapted to releasably lock the top cover in the closed configuration in order to maintain the gas-tight seal between the top cover and the animal compartment.

In a further embodiment of the invention, the chamber includes a top cover guide which controls the movement of the top cover when it is being moved between its open and closed configurations. The guide typically controls the top cover such that it is spaced vertically from the animal compartment in the open configuration.

In this embodiment, a user has access to the animal compartment when the top cover is in the open configuration such that the contents of the animal compartment may be modified or the animal compartment may be replaced in its entirety without disrupting the functional elements of the metabolic chamber, all of which are carried by the top cover.

The guide may include an energy storage system which is charged when the top cover is in the closed configuration and which assists the movement of the top cover to the open configuration by releasing its stored energy during the movement. Additionally or alternatively, the guide may be powered to assist the movement of the top cover. Furthermore, the guide may include a damper system that damps the motion of the top cover when being moved between the open and closed configurations. Such an arrangement would prevent damage to the animal compartment in the event that the top cover is accidentally released by a user.

In embodiments where the top cover includes a releasable lock, the lock may engage a complimentary element of the top cover guide in order to releasably lock the top cover in its open and/or closed configuration.

According to a further embodiment, the feeding station includes a food hopper which is connected, either directly or indirectly, to a mass measurement apparatus. This allows the weight of the food consumed by the test subjects to be measured. The mass measurement apparatus may include a mass balance, such as, for example, a load cell. The mass measurement apparatus may be connected to a local controller and/or data collector, where present.

The feeding station may have a feeding configuration in which access to food in the food hopper is permitted and a non-feeding configuration in which access to the food is prevented. It may also have one or more limited access configurations in which access to the food is restricted.

It is useful for users to be able to control the access to food of the test subjects, as feeding is an important parameter for many animal experiments.

In an embodiment of the invention, the feeding station includes a food cover having a feeding position in which access to the food within the food hopper is permitted and a non-feeding position in which access to the food is prevented. The food cover may also have one or more intermediate positions in which access to the food is restricted. In such an embodiment, the food cover may move relative to the food hopper or the food hopper may move relative to the food cover.

In a further embodiment, the food cover is adapted to rotate relative to the food hopper between the feeding and non-feeding positions (and optionally one or more positions in between). In such embodiments, the food cover may comprise a generally cylindrical body which defines therein one or more apertures, wherein the body wall prevents access to the food hopper and the or each aperture permits access to the food hopper.

In a yet further embodiment, the food hopper has a circular cross-section and the food cover comprises a generally cylindrical body which defines therein one or more apertures, wherein the food cover is arranged concentrically around the food hopper and is adapted to rotate relative thereto.

The access to the food hopper may be controlled manually by a user or it may be controlled remotely via a motor (such as an electric or hydraulic motor). The motor may be connected to a controller such that access is permitted to food within the hopper only at pre-determined times of the day and/or only for pre-determined periods of time. The controller may form part of the local controller where present.

Thus, the food cover as described anywhere above may be moved manually by a user or it may be coupled to a motor and controlled remotely.

Alternatively, where the access to food is controlled without a food cover, e.g. by raising and lowering the food hopper relative to the animal compartment, the food hopper may be raised or lowered manually or remotely via a motor.

In embodiments where the access to the food is controlled remotely, the chamber may include a motor as discussed above and a controller to control the motor. The controller may include one or more sensors to sense the degree of access to the food that is available to the test subjects. For example, where the access is controlled by a food cover, the controller may include an optical position detector to sense the position of the cover.

The feeding station may include a food hopper support provided in the top cover. The support may define an aperture (e.g. an aperture having a circular shape) within which the food hopper is supported. In such an arrangement, the food hopper may include a body and a flange extending radially outwardly from an upper portion of the body, whereby the body may be located within the aperture of the support and the flange may engage an upwardly facing peripheral edge portion about the aperture of the support.

In an arrangement in which the food hopper is supported by a hopper support provided in the top cover, the food hopper can be removed and replaced easily without having to open the top cover.

The food hopper support may include a load cell, such as for example a load cell using strain gauge technology, which is capable of measuring the weight of the food contained within the food hopper.

This means that the food hopper need not include delicate instruments to measure the weight of the food contained therein and that different hoppers can be used with the chamber, provided they are adapted to be supported by the hopper support. The load cell may be connected to the local controller and/or a data collector where present.

In a further embodiment, the food hopper support may provide a key adapted to engage a corresponding lock element provided on the food hopper, such that a hopper supported by the support can only be located in the support in a specific orientation.

In a further embodiment, the top cover may include two or more feeding stations depending therefrom, wherein each feeding station independently may be as defined anywhere herein.

The advantage of providing two separate feeding stations is that different foods can be utilised or a test food and a control food can be utilised in a single chamber. Additionally or alternatively, the two or more feeding stations can contain different foods and a preference for one food over another may be determined for the test subjects.

A fluid station may be provided in the top cover, in addition to the feeding station(s). The arrangement of the fluid station may be as defined anywhere herein in connection with the feeding station, wherein the food hopper is replaced by a fluid container. Thus, the fluid station may include a mass measurement apparatus, a fluid container support, etc., all as defined above in connection with the feeding station.

In an embodiment of the invention which includes both one or more feeding stations and one or more fluid stations, wherein the or each feeding station and the or each fluid station includes a support, the supports may include respective apertures which have different dimensions or configurations that are specific to the respective food hopper and fluid container. Thus, the food hopper(s) and the fluid container(s) are always located in the same position on the top cover such that the test subjects become accustomed to this arrangement.

In embodiments which comprise a top cover including a fluid station which in turn includes a mass measurement system, it is possible to use standard fluid containers, which have been adapted to engage a fluid container support. In this way, the test subjects are already accustomed to drinking from a standard fluid container and are not confused or stressed when placed in the metabolic chamber according to the invention. For example, the test subjects do not need to be trained where to obtain fluids and/or how to obtain the fluids from the fluid dispenser. As an alternative, a custom fluid container including a standard fluid dispenser, e.g. drinking spout, may be used.

The feeding station(s) and/or the fluid station(s) may include a lid. Each station may include a respective lid or a single lid may be capable of covering two or more stations. The lid(s) helps to prevent contamination of the food and /or fluids. The lid(s) may also prevent accidental damage to or false readings from the mass measurement apparatus, where present. Furthermore, the lid(s) may provide a gas-tight seal with the top cover.

The lid(s) may be hinged and include a closed configuration in which access to the feeding station(s) and/or the fluid station(s) is prevented, and an open configuration in which access to the feeding station(s) and/or the fluid station(s) is permitted. Thus, in the closed configuration, a gas-tight seal may be provided and in the open configuration, a user may access the feeding station(s) and/or the fluid station(s) in order to replenish their contents or to change their contents. The changing of the contents may be achieved by replacing a food hopper or a fluid vessel. Thus a food hopper and/or a fluid vessel can easily be swapped for a different one.

In a further embodiment of the invention as defined anywhere herein, the top cover includes an illumination arrangement, including at least one light emitting element and a light controller. In embodiments where the illumination arrangement includes a plurality of light emitting elements, it may include light emitting elements of different colours, for example, white, red and/or blue.

The light emitting elements may be any type of known elements, such as LED5 and/or electric filament bulbs which may or may not include colour filters.

The light controller may permit manual control of the ambient lighting environment within the metabolic chamber or it may be programmable to provide lighting conditions according to a pre-defined protocol. Suitably, the controller includes a programmable processor such that the illumination arrangement is capable of being controlled automatically (i.e. without repeated intervention from a user).

In a further embodiment, the metabolic chamber includes one or more motion sensors adapted to sense movement of the test subjects within the animal compartment. The chamber may include one or more arrays of sensors, such that two-dimensional or three-dimensional movement of the test subjects may be monitored. The motion sensor(s) may be carried by the top cover. Alternatively, they may be provided about the animal compartment.

In an addition or as an alternative to the motion sensors, the chamber may include one or more still and/or video cameras adapted to capture movement and behaviour of the test subjects. The camera(s) may be connected to a recording device and/or may be controlled remotely.

In addition to the components discussed above, the chamber may include further components typically found in metabolic chambers. These may include, for example, a gas monitoring apparatus.

The gas monitoring apparatus typically includes a gas outlet pipe adapted to draw a gas flow from the animal compartment and a gas analyser adapted to analyse the gas flow. The metabolic chamber may recycle the air, in which case a gas return pipe is provided downstream of the analyser which is adapted to return the gas flow to the chamber. Alternatively, the gas flow may be exhausted to the atmosphere after having been analysed and the chamber may include a fresh air inlet.

As with the embodiments described hereinabove, the further components may also carried by the top cover.

The metabolic chamber of the present invention may form part of an array of chambers, wherein the array comprises two or more metabolic chambers according to the first aspect of the invention.

The nature of the chambers in the array is such that individual chambers may be replaced within the array or animal compartments from individual chambers may be removed or replaced without disrupting the remainder of the chambers within the array.

The array may include a chamber support element, wherein each of the individual chambers is engaged with the support element. For example, the support element may be a vertical support element which provides support for a one-or two-dimensional array of chambers arranged vertically.

The array may include a central control unit to which is connected each of the chambers, such that all of the functions of the individual chambers can be controlled by the central control unit.

The skilled person will appreciate that the features specified above in connection with embodiments of the invention may be combined with each other and any of the aspects of the invention as defined. Thus, the present invention includes within its scope an aspect of the invention combined with two or more of the features described anywhere herein as optional features. All such combinations of features described herein are considered to be made available to the skilled person An embodiment of the invention will now be described in detail, by way of example only, with reference to the accompanying drawings in which: Figure 1 is a perspective view from beneath a top cover forming part of the invention; Figure 2 is a perspective view from above the top cover of Figure 1; Figure 3 is a perspective view of a top cover showing lids covering parts of the top cover; Figure 4 is a perspective view of a metabolic chamber according to the invention in which the top cover is in an open configuration; Figure 5 is a perspective view of a metabolic chamber according to the invention in which the top cover is in a closed configuration.

For the avoidance of doubt, the skilled person will appreciate that in this specification, the terms "up", "down", "front", "rear", "upper", "lower", "width", etc. refer to the orientation of the components as found in the metabolic chamber when installed for normal use as shown in the Figures.

Figure 1 shows a top cover 2 for a metabolic chamber according to the invention. The top cover consists of a body 4 which carries various components of the metabolic chamber. The body 4 defines two feeding station apertures 6, 10 and a fluid station aperture 14. It also defines a lighting aperture 32.

Located within the feeding station apertures 6, 10 are respective feeding stations. The feeding stations comprise a food hopper 28, 30 surrounded by a cylindrical shaped cover 8, 12. The food hoppers 28, 30 are also cylindrical in shape and are arranged concentrically within their respective cover 8, 12. The covers 8, 12 each have a body 20, 22 which defines a respective aperture 24, 26. The apertures 24, 26 are vertically aligned with an access port of the food hoppers 28, 30 and the covers 8, 12 are adapted to rotate relative to the hoppers 28, 30, which are held stationary.

Located within the fluid station aperture 14 is a fluid station in the form of a standard water bottle 16 which includes an outlet spout 18. Such water bottles are well known in the art and will not be described in detail herein.

The top cover further includes a fan 19 which is capable of circulating the air around the chamber 2.

Located on a downwardly facing peripheral surface of the top cover 2 is a rubber seal or gasket 34.

A more detailed description of the feeding stations and the fluid station will now follow with reference to Figure 2.

The top cover body 4 includes a cylindrical support 44, 46 surrounding each aperture 6, 10. Located within each support 44, 46 is a respective cover 8, 12. The uppermost portion of the body 20, 22 of each cover 8, 12 terminates in a flange 48, 50. Each flange 48, 50 includes four notches 58.

Each support 44, 46 includes four upwardly projecting locating pins 52 which are unevenly spaced about the circumference of the supports 44, 46. The notches 58 of the cover flanges 48, 50 are arranged to receive the locating pins 52. As the locating pins 52 are unevenly distributed about the circumference of the supports 44, 46, the covers 8, 12 can only be located within their respective supports in a single orientation.

The supports 44, 46 include bearings (not shown) that permit the supports 44, 46 to rotate relative to stationery base elements 45, 47 which are fixed to the top cover body 4. The supports 44, 46 include respective optical discs 54, 56 which are annular discs that include slots 55, 57. The top cover body 4 includes optical sensors (not shown) which detect the angular displacement of the optical discs 54, 56 via the slots 55, 57 and hence senses the angular displacement of the supports 44, 46. As the covers 8, 12 are keyed to the supports 44, 46 via the locating pins 52, the optical sensors are able to sense the position of the covers and determine if the test subjects have access to the food hoppers 28, 30.

The food hoppers 28, 30 (not shown in Figure 2) are partly located within the body 20, 22 of a respective cover 8, 12, which in turn are partly located within a respective support 44, 46, such that each support 44, 46 is arranged concentrically about a portion of the respective cover 8, 12 and food hopper 28, 30.

The rotation of the covers 8, 12 and their associated supports 44, 46 is effected by respective motors (not shown). Each motor drives a shaft which carries an external worm gear which in turn engages respective teeth formed on an outward facing gear wheel provided on each support 44, 46 (the shaft, worm gear and gear wheel are not shown in Figure 2). However, the skilled person will appreciate that the rotation of a cylinder by a motor about its longitudinal axis is well known. Accordingly, such an arrangement will not be described in detail herein. The motors are electric motors and their operation is controlled by a controller (also not shown). Again, the control of electric motors is well known.

The food hoppers 28, 30 are carried by respective annular carriers (not shown). Each food hopper 28, includes a flange extending outwards from the uppermost part of its body and the flange is sized to overly the body of the respective annular carrier, whereby the body of each food hopper 28, 30 passes through the aperture defined by the respective annular carrier and the flange is support by the body of the annular carrier. Each annular carrier includes a lock element which engages a corresponding key element carried by the respective food hopper 28, 30. This arrangement ensures that the food hoppers 28, 30 are always aligned with the respective carrier in a pre-determined orientation.

Each annular carrier is connected to respective precision load cell 40, 42 which uses strain gauge technology to weigh accurately the food hopper and its associated contents. Such precision load cells are known in the art and will not be described in detail herein. The load cells 40, 42 are arranged to measure the force exerted downwardly upon each annular carrier by the respective food hopper 28, 30. In this way, the weight of each food hopper 28, 30 is measured by the respective precision load cell and the amount of food that has been consumed from each food hopper 28, 30 by the test subjects can be calculated.

A similar arrangement exists for the water bottle 16. A flange 59 is provided about the body of the water bottle 16, which contacts an upwardly facing surface of a water bottle carrier (not shown). The water bottle carrier is connected to a precision load cell in the same way that the food hopper carriers are connected to strain gauges.

Figure 3 shows the top cover 2 with protective lids 60, 62 protecting the functional components of the metabolic chamber.

The lid 60 covers the feeding stations and the fluid station. It rotates about a hinge 68 and includes an electromagnetic lock comprising an electromagnetic unit 66 and a ferrous receiver 64. The electromagnetic unit 66 is connected to an electrical current source via a controller. Electromagnetic locks as used in this example are well known and commercially available. However, the skilled person will appreciate that additionally or alternatively the lid 60 may be held closed by the action of gravity or by a mechanical lock.

The lid 62 covers an array of LEDs, together with a controller which controls the lighting levels in an animal compartment below. The LEDs are a mixture of white and red LEDs. These additional components are common in metabolic chambers and are well known to a skilled person.

Figures 4 and 5 shows a metabolic chamber including the top cover 2, an animal compartment 80 and a top cover guide 70.

The animal compartment 80 is located within a frame 82 secured to a base 84 to ensure a consistent positioning of the animal compartment 80 within the chamber and to prevent accidental movement of the animal compartment 80 relative to the top cover 2 such that the gas-tight seal is broken.

The top cover 2 includes a frame consisting of parallel side arms 76 and a handle 78 which joins the two side arms 76 at the distal ends thereof.

The proximal ends of the side arms 76 are slidably coupled to respective vertical tracks 72, 74 of the guide 70 such that the top cover can slide vertically relative to the guide towards and away from the animal compartment 80.

The vertical tracks 72, 74 of the guide 70 include a first electromechanical lock (not shown) which secures the side arms 76 at the top of their permitted vertical travel when operated and a second electromechanical lock (not shown) which secures the side arms 76 at the bottom of their permitted vertical travel when operated. Again, the skilled person will appreciate that mechanical locks may be used in place of the electromechanical locks and that the second electromechanical lock may be omitted where a suitable seal may be obtained by the action of gravity on the top cover 2, i.e. the second electromechanical lock may be omitted where the weight of the top cover 2 is sufficient to provide a gas-tight seal with the animal compartment 80.

The vertical tracks 72, 74 also include dampers (not shown) to damp the movement of the side arms 76.

In the open configuration of the metabolic chamber as shown in Figure 4, the top cover 2 is vertically spaced from the animal compartment 80 and is locked in this position. Figure 5 shows the chamber in a closed configuration.

In use, an animal compartment 80 containing test subjects which have been acclimatised to the compartment is placed within the frame 82. The first electromechanical lock is released and the top cover 2 is lowered via the side arms 76 and tracks 72, 74 onto the top of the animal compartment 80.

The second electromechanical lock secures the top cover 2 in place with sufficient force that the rubber seal 34 provides a gas-tight seal between the animal compartment 80 and the top cover 2.

When access to food within the food hoppers 28, 30 is permitted, the covers 8, 12 are rotated until the apertures 24, 26 align with respective access ports of the food hoppers 28, 30. Rotation of the cover 8, 12 is achieved via the electrical motors, the worm drive shaft and the gear wheel carried by the supports 44, 46 and the position of the covers 8, 12 relative to the food hoppers 28, 30 is sensed by the optical position sensors.

When it is desired to prevent access to the food, the covers 8, 12 are rotated such that the apertures 24, 26 no longer align with the access ports of the food hoppers 28, 30.

As food is consumed by the test subjects, the force exerted by the food hoppers 28, 30 on their respective annular carriers decreases and this decrease in force is sensed by the precision load cells connected to the carriers. In this way, the weight of food consumed is measured. Similarly, the volume of fluid consumed is measured via the reduction in force exerted by the water bottle 16 on its carrier.

If it is desired to access the food hoppers 28, 30 or the water bottle 16, this is achieved by releasing the lid 60 and opening it about its pivot 68. The food hoppers 28, 30 can then be removed by lifting them vertically out of their annular carriers. Replacement food hoppers 28 30 can then be inserted into the carriers.

Similarly, the water bottle 16 may be replaced or re-filled by removing it from its carrier vertically and then re-inserting a replacement bottle 16 or a re-filled bottle back into the carrier.

Once the food hoppers and/or water bottle have been replaced or re-filled, the lid 60 is closed and secured with the minimum of stress to the test subjects and inconvenience to the user.

Access to the animal compartment 80 is achieved by releasing the second electromechanical lock and raising the top cover along the tracks 72, 74, at which point, it can be secured in its open configuration by activation of the first electromechanical lock.

Claims (14)

1. Claims 1. A metabolic chamber including an animal compartment and a top cover, wherein the top cover contains at least one feeding station depending therefrom.
2. 2. A metabolic chamber according to Claim 1, wherein the top cover has an open configuration, in which it is spaced from the animal compartment, and a closed configuration in which it forms a gas-tight seal with the animal compartment.
3. 3. A metabolic chamber according to Claim 2, wherein the top cover includes a releasable lock adapted to releasably lock the top cover in the open configuration.
4. 4. A metabolic chamber according to Claim 2 or Claim 3, wherein the top cover includes a gasket or seal located about its downwardly facing periphery, whereby in use, the gasket or seal is trapped between the top cover and the animal compartment to provide the gas-tight seal there between.
5. 5. A metabolic chamber according to any preceding claim, wherein the feeding station includes a food hopper which in use contains food.
6. 6. A metabolic chamber according to Claim 5, wherein the food hopper is connected, either directly or indirectly, to a mass measurement apparatus.
7. 7. A metabolic chamber according to Claim 5 or Claim 6, wherein the feeding station has a feeding configuration in which access to food in the food hopper is permitted and a non-feeding configuration in which access to the food is prevented.
8. 8. A metabolic chamber according to Claim 7, wherein the feeding station includes a food cover which selectively permits or denies access to the food in the food hopper.
9. 9. A metabolic chamber according to Claim 8, wherein the food hopper has a circular cross-section and the food cover comprises a generally cylindrical body which defines therein one or more apertures, wherein the food cover is arranged concentrically around the food hopper and is adapted to rotate relative thereto.
10. 10. A metabolic chamber according to any preceding claim, wherein the top cover includes two or more feeding stations depending therefrom.
11. 11. A metabolic chamber according to any preceding claim, wherein the top cover further includes a fluid station depending therefrom.
12. 12. A metabolic chamber according to any preceding claim further including a lid having a closed configuration in which it covers the feeding station and prevents access thereto and an open configuration in which access is permitted to the feeding station.
13. 13. A metabolic chamber according to Claim 12, wherein the lid is hingedly coupled to the top cover and includes a releasable lock adapted to releasably secure the lid in the closed configuration.
14. 14. An array of metabolic chambers, the array comprising two or more metabolic chambers according to any of Claims 1 to 13.