AN APPARATUS

Abstract

An apparatus suitable for handling biological material, for directly introducing or removing material to, or from, a container, comprising a body comprising at least one resealable port; a cover comprising an aperture and wherein the cover is disposed over an upper side of the body, and wherein the cover is moveable such that an aperture of the cover is configured to expose at least part of the resealable port.

Claims

1. An apparatus suitable for use in handling biological material, for directly introducing or removing material to, or from, a container, comprising: a body comprising at least one resealable port therein; and a cover comprising an aperture and wherein the cover is disposed over an upper side of the body, and wherein the cover is moveable, the aperture of the cover is configured to expose at least part of the resealable port, when the aperture is disposed over the resealable port.

2. An apparatus according to claim 1, wherein the body comprises an upper surface and a lower surface, the cover is disposed over the upper surface, and the at least one resealable port extending through the body from the upper surface to the lower surface.

3. An apparatus according to claim 2, wherein the body comprises a plurality of longitudinal passageways extending from the upper surface to a recess formed in the lower surface, each longitudinal passageway comprising a resealable port and an annular recess comprising an annular resealable port.

4. An apparatus according to claim 3, wherein each resealable port in each longitudinal passageway and the annular resealable port are integrally formed.

5. An apparatus according to claim 1, wherein the at least one resealable port is a hermetic seal.

6. An apparatus according to claim 5, wherein the hermetic seal is a septum seal.

7. The apparatus according to claim 6, wherein the septum seal and the body are co-molded.

8. The apparatus according to claim 1, the cover further comprising a connector mechanism for connecting to a portion of a container, a bioreactor or a connector.

9. The apparatus according to claim 8, wherein the connector mechanism comprises a threaded portion configured to engage with a corresponding threaded portion of a container, a bioreactor or a connector.

10. The apparatus according to claim 1, wherein the cover comprises a centrally disposed opening at least partly surrounded by an upstanding wall.

11. The apparatus according to claim 10, wherein the body comprises a central hub having a coupling element, the central hub extending through the centrally disposed opening and the coupling element operably coupled to the upstanding wall.

12. The apparatus according to claim 1, wherein the cover comprises a circumferential skirt that is configured and arranged to removably attach to a circumferential rim of the body.

13. The apparatus according to claim 1, wherein the cover comprises a substantially circumferential rail that is configured and arranged to be received within a substantially circumferential groove of the body.

14. An apparatus according to claim 1, wherein the cover and the body are rotatable with respect to one another.

15. An apparatus according to claim 1, wherein a lower surface of the body includes a connector mechanism for connecting to a portion of a container, a bioreactor or a connector.

16. An apparatus according to claim 15, wherein the connector mechanism is a threaded portion configured to engage with a corresponding threaded portion of a container, a bioreactor or a connector, the threaded portion comprising an anti-rotational element configured and arranged to resist rotation of a container, a bioreactor or a connector, in use.

17. An apparatus according to claim 16, wherein the anti-rotational element comprises one or more trapezoidal threads of the threaded portion.

18. An apparatus according to claim 1, further comprising a detachable cover disposed over at least a portion of the at least one resealable port.

19. A system suitable for use in handling biological material comprising: an apparatus suitable for use in handling biological material, for directly introducing or removing material to, or from, a container, the apparatus comprising: a body comprising at least one resealable port therein; and a cover comprising an aperture and wherein the cover is disposed over an upper side of the body, and wherein the cover is moveable, the aperture of the cover is configured to expose at least part of the resealable port, when the aperture is disposed over the resealable port. ; and a container, a bioreactor and/or a connector sealingly engaged with the at least one resealable port.

20. A method of operating an apparatus suitable for use in handling biological material, for directly introducing or removing material to, or from, a container, comprising: providing an apparatus suitable for use in handling biological material, for directly introducing or removing material to, or from, a container, the apparatus comprising: a body comprising at least one resealable port therein; and a cover comprising an aperture and wherein the cover is disposed over an upper side of the body, and wherein the cover is moveable, the aperture of the cover is configured to expose at least part of the resealable port, when the aperture is disposed over the resealable port; sealingly engaging a first container to the at least one resealable port at a lower surface of the body; sealingly engaging a second container to the at least one resealable port at an upper surface of the body; providing fluid communication between the container and the bioreactor by providing a fluid passageway through the at least one resealable port; and introducing material from the second container into the first container, or removing material from the first container into the second container.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0128] These and other aspects, features and advantages of which embodiments of the disclosure are capable of, will be apparent and elucidated from the following description of example embodiments and aspects of the present disclosure, reference being made to the accompanying drawings, in which:

[0129] FIG. 1 illustrates a perspective view of a body of the apparatus according to the present disclosure;

[0130] FIG. 2 illustrates the body of FIG. 1 from below;

[0131] FIG. 3 illustrates the body of FIG. 1 having a plurality of aseptic paper seals attached;

[0132] FIG. 4 illustrates a perspective view of a cover of the apparatus according to the present disclosure;

[0133] FIG. 5 illustrates the cover of FIG. 4 from below;

[0134] FIG. 6 illustrates a perspective view of a system, including the apparatus according to the present disclosure, and an aseptic connector and a container attached thereto;

[0135] FIG. 7 illustrates a cross-sectional view of the apparatus according to the present disclosure, including a container attached thereto;

[0136] FIG. 8 illustrates an enlarged view of FIG. 7;

[0137] FIG. 9 illustrates a cross-sectional view of the system as shown in FIG. 6;

[0138] FIG. 10 illustrates a container for use with the apparatus according to the present disclosure;

[0139] FIG. 11a illustrates a perspective view of a system having the apparatus according to the present disclosure and a container attached thereto, and an aseptic connector before a connection is made to the apparatus, and FIG. 11b illustrates a top view of FIG. 11a;

[0140] FIG. 12a illustrates a perspective view of the system of FIGS. 11a and 11b having an aseptic connector attached to the apparatus, and FIG. 12b illustrates a top view of FIG. 12a;

[0141] FIG. 13a illustrates a perspective view of the system of FIGS. 12a and 12b having aseptic paper seals removed, and FIG. 13b illustrates a top view of FIG. 13a;

[0142] FIG. 14a illustrates a perspective view of the system of FIGS. 13a and 13b once the aseptic connector has been removed from the apparatus, and FIG. 14b illustrates a top view of FIG. 14a;

[0143] FIG. 15a illustrates a perspective view of the system of FIGS. 11a to 14b after use, and FIG. 15b illustrates a top view of FIG. 15a;

[0144] FIG. 16a illustrates a perspective view of the system of FIGS. 15a and 15b once rotated in the direction indicated, and FIG. 16b illustrates a top view of FIG. 16a;

[0145] FIG. 17a illustrates a perspective view of the system of FIGS. 16a and 16b, including the apparatus according to the present disclosure and a container attached thereto, and an aseptic connector before a connection is made to the apparatus, and FIG. 17b illustrates a top view of FIG. 17a;

[0146] FIG. 18a illustrates a perspective view of the system of FIGS. 17a and 17b having an aseptic connector attached to the apparatus, and FIG. 18b illustrates a top view of FIG. 18a;

[0147] FIG. 19a illustrates a perspective view of the system of FIGS. 18a and 18b having aseptic paper seals removed, and FIG. 19b illustrates a top view of FIG. 19a;

[0148] FIG. 20 illustrates a perspective view of a system according to the present disclosure with an apparatus partially loaded therein;

[0149] FIG. 21 illustrates a perspective view of a mounting bracket, actuators and frictional drive mechanism of the system of FIG. 20; and

[0150] FIG. 22 illustrates a top view of the mounting plate and the frictional drive mechanism of the system of FIG. 21.

DETAILED DESCRIPTION

[0151] The described example embodiments relate to an apparatus for directly introducing or removing material to or from a container. Other embodiments relate to a system and a method for introducing or removing material to or from a container, either manually or in a semi-automated or an automated manner. Further embodiments, examples, aspects and advantages will become apparent through the remaining description.

[0152] Certain terminology is used in the following description for convenience only and is not limiting. The words “upper” and “lower” designate directions in the drawings to which reference is made and are with respect to the described component when assembled and mounted. The words “inner,” “inwardly,” “outer,” and “outwardly” refer to directions toward and away from, respectively, a designated centerline or a geometric center of an element being described (e.g., a central axis), the particular meaning being readily apparent from the context of the description. Further, the terms “proximal” (i.e., nearer to) and “distal” (i.e., away from) designate positions relative to an axis or a point of attachment.

[0153] Further, as used herein, the terms “connected,” “affixed,” “coupled” and the like are intended to include direct connections between two members without any other members interposed therebetween, as well as, indirect connections between members in which one or more other members are interposed therebetween. The terminology includes the words specifically mentioned above, derivatives thereof, and words of similar import.

[0154] Further, unless otherwise specified, the use of ordinal adjectives, such as, “first,” “second,” “third,” etc., merely indicate that different instances of like objects are being referred to and are not intended to imply that the objects so described must be in a given sequence, either temporally, spatially, in ranking or in any other manner. Like reference numerals are used to depict like features throughout.

[0155] As best shown in FIGS. 1 to 9, there is provided an apparatus 100 including a body 200 and a cover 300. The body 200 or the cover 300 or both the body 200 and the cover 300 may be moveable with respect to one another. In the depicted example, the cover 300 is slidably mountable to the body 200 such that the body 200 or the cover 300 may be rotated with respect to one another.

[0156] Referring more specifically to FIGS. 1 to 3, the body 200 includes an upper surface 202 and a lower surface 204 and is generally circular and planar. The body 200 further includes a central hub 210 upstanding from the upper surface 202 of the body 200 along a central longitudinal axis. The central hub 210 includes a coupling element, formed as a plurality of hooks 212, at a distal end thereof. Each hook of the plurality of hooks 212 are configured to engage with a corresponding portion of the cover. Specifically, the hooks 212 in the depicted embodiment are clipped, via a snap-engagement mechanism, to an upstanding wall of the cover, as described further below. The central hub 210 may also include an annular ring 214 surrounding and enclosing the central hub 210, the annular ring 214 being coaxial with the central hub 210 and extending from the upper surface 202. Additionally, although not shown in the present example, the central hub 210 includes a further coupling element, formed interiorly of the central hub 210, configured and arranged to allow coupling of the central hub 210, and thus the body 200 and apparatus 100, to a container, which generally forms part of a breathing mechanism. Such further coupling element is provided by screw threads or a clip that is configured and arranged to cooperate with corresponding screw threads or a clip of the container.

[0157] The upper surface 202 of the body 200 includes a plurality of longitudinal passageways 216 extending from the upper surface 202 longitudinally into the body 200. The lower surface 204 of the body 200 includes a generally annular recess 218 having screw threads 220. The lower surface 204 of the body 200 also includes a plurality of radial ribs 222 extending from the annular recess 218 towards an outer edge of the body 200. Each of the plurality of longitudinal passageways 216 extend from the upper surface 202 to the annular recess 218 on the lower surface 204.

[0158] The screw threads 220 are configured and arranged to receive a corresponding threaded portion of a corresponding container. The screw threads 220, as best shown in FIGS. 2 and 8, include an anti-rotational element, formed as a trapezoidal thread 221 as best shown in FIG. 8, configured and arranged to resist rotation of an attached container. The trapezoidal thread 221 includes an upper thread surface, a side surface and a lower thread surface. The lower thread surface forms an inclination angle with the longitudinal axis of between approximately 20 degrees and approximately 80 degrees. In some examples, the inclination angle may be between approximately 30 degrees and approximately 50 degrees. In other examples, the inclination angle may have a lower limit of approximately 20, 30, 40, 50, 60 or 70 degrees, or any integer therebetween, and an upper limit of approximately 30, 40, 50, 60, 70 or 80 degrees, or any integer therebetween. As will be appreciated by the person skilled in the art, other anti-rotational elements may also be used.

[0159] The body 200 also includes a plurality of resealable ports, formed as a septum seal member 230 in the depicted embodiment. In this embodiment, the septum seal member 230 includes, through the resealable ports, a plurality of protruding upper portions 232 facing the cover direction. The septum seal member 230 comprises protruding upper portions 232 extending longitudinally from an upper surface of a generally annular portion 234 of the septum seal member 230. That is, the septum seal member 230 has an integrally formed plurality of protruding upper portions 232 and a generally annular portion 234.

[0160] Additionally, the body 200 includes a plurality of aseptic paper seals 240, as best shown in FIG. 3, each aseptic paper seal 240 disposed over the uppermost, exposed, surface of each of the protruding upper portion 232 of the septum seal member 230. Each aseptic paper seal 240 includes an aseptic membrane 242 and a handle 244 extending therefrom. Each aseptic paper seal 240 serves to maintain an aseptic uppermost surface of each of the protruding upper portion 232 and thus the upper surface portion of the septum seal member 230.

[0161] The body 200 also includes a circumferential skirt 250 at the outermost edge 252 of the body 200, the outermost edge 252 extending between the upper surface 202 and the lower surface 204. The circumferential skirt 250 includes one or more circumferential grooves 254 for receiving a portion of the cover 300, as described below.

[0162] Referring now to FIGS. 4 and 5, the cover 300 includes an upper surface 302 and a lower surface 304. The upper surface 302 includes an upstanding wall 305 enclosing a centrally disposed opening 306. The upstanding wall 305 is surrounded by a circumferential flange 308. The upper surface 302 also includes a connector mechanism 310 for connecting, for example, a container to an upper surface 302 of the cover 300. The connector mechanism 310 at least partially surrounds at least a portion of an aperture 312 formed within the upper surface 302 of the cover 300.

[0163] The connector mechanism 310 can be formed in any appropriate way, for example, as a threaded portion or the like. In the described embodiment, the connector mechanism 310 includes a wall 314 upstanding from the upper surface 302 of the cover 300, and a plurality of legs 316 protruding outwardly from the wall 314, each leg 316 having a protrusion 318 at a distal end. The protrusions 318 are configured and arranged to mate with a corresponding groove of, for example, a container, a connector or the like, when connected to the connector mechanism 310.

[0164] The lower surface 304 of the cover 300 includes a centrally disposed annular recess 350 enclosing the centrally disposed opening 306. The lower surface 304 of the cover 300 also includes a generally circumferential rail 352 configured and arranged to be received within the substantially circumferential grooves 254 of the body 200, as described below.

[0165] The cover 300 also includes a generally circumferential skirt 360 longitudinally extending from the upper surface 302 towards and past the lower surface 304, thereby forming an overhanging portion. The circumferential skirt 360 includes a plurality of cut out portions 362 each having a hook portion 364 at a distal end thereof. The hook portions 364 are configured and arranged to clip to the body 200, as described below.

[0166] In use, in this embodiment, the cover 300 is secured to the body 200, for example, clipped to the body 200, such that the cover 300 and the body 200 are slidable with respect to one another. In particular, as best shown in FIGS. 6 to 9, the cover 300 is clipped to the body 200 such that the circumferential skirt 360 surrounds the outermost edge 252 of the body 200, and such that the hook portions 364 are clipped, for example, by a snap engagement, with lower surface 204 of the body 200. The circumferential rail 352 of the cover 300 is received within the circumferential groove 254 of the body 200. Thus, the cover 300 and the body 200 are provided to be moveable in a sliding and rotatable manner.

[0167] Furthermore, the central hub 210 of the body 200 extends through the centrally disposed opening 306 such that the hooks 212 of the body 200 are clipped, for example, by a snap engagement, with a distal edge of the upstanding wall 305. Additionally, the annular ring 214 of the body 200 is received within the centrally disposed annular recess 350 of the cover 300.

[0168] As best shown in FIGS. 6 and 14b, the aperture 312 exposes one of the protruding upper portions 232 of the septum seal member 230 formed within the body 200. Thus, the aperture 312 exposes at least a portion of the at least one resealable port. The remainder of the cover 300 generally covers the remaining, or at least a portion, of the protruding upper portion 232 of the septum seal member 230. Thus, the cover 300 or the body 200 may be rotated, i.e., in a slidable manner, to expose a number of protruding upper portion 232 of the septum seal member 230. Aptly, in this embodiment, the cover is slid or rotated, with the body stationary, to expose through the aperture a desired resealable port. Specifically, in this embodiment, the cover is slid or rotated, with the body stationary, to expose through the aperture a desired protruding upper portion 232 of the septum seal member 230.

[0169] In another embodiment, the cover 300 may remain stationary and the body 200 is caused to rotate.

[0170] As shown in FIGS. 7 to 10, a container 500, having a thread 502 and a volume of fluid 504, is threadedly engaged with the corresponding screw thread 220 of the body 200. In this way, the container 500 is sealingly engaged at an upper edge thereof, adjacent the thread 502, to the lower surface 204 of the septum seal member 230. The sealing engagement may be a hermetic or liquid seal. The body 200 is then rotated such that one of the protruding upper portion 232 of the septum seal member 230 formed within the body 200 is exposed, when the protruding upper portion 232 of the septum seal member 230 is aligned with the aperture 312. A container or a connector is then engaged with the connector mechanism 310 of the cover 300.

[0171] Referring to FIGS. 9 and 11a to 13b, an aseptic connector 400 is connected to the connector mechanism 310. Specifically, an outer sleeve 402 of the aseptic connector 400 includes a circumferential groove 403 that receives the protrusions 318 of each leg 316 of the connector mechanism 310 (see FIG. 4). The aseptic connector 400 also includes an aseptic paper seal 404 (see FIGS. 12a and 12b), the aseptic paper seal 404 comprises a handle and an aseptic membrane. The aseptic paper seal 404 of the aseptic connector 400 is able to align with the aseptic paper seal 240 of the body that is exposed within the aperture 312. The user then removes the aseptic paper seals 240, 404 by pulling the respective handles 244, 406 to allow abutment of the protruding upper portion 232 of the resealable port and a septum seal of the aseptic connector 400.

[0172] The user actuates the aseptic connector 400, and/or the container 500, such that a fluid connection between the aseptic connector 400 and the container 500 can be made. For example, in the depicted example, the aseptic connector 400 is actuated such that a hollow needle pierces the seal, thereby providing an aseptic fluid pathway between the aseptic connector 400, and the container 500. In a subsequent step, fluid can be introduced, or removed, from the container attached to the aseptic connector 400 and/or the container 500. The aseptic connector may, for example, be part of a container or be connected to another container.

[0173] As shown in FIGS. 14a to 16b, the aseptic connector 400 is then removed by pressing the legs 316 of the connector mechanism 310 (see FIG. 4) together and pulling the aseptic connector 400 in a longitudinal direction away from the upper surface 302 of the cover 300. The cover 300 can then be rotated in direction A to expose the next protruding upper portion 232 of the septum seal member 230, covered by the aseptic paper seal 240, in the aperture 312. The process can then be repeated, as shown in FIGS. 17a to 19b.

[0174] A system 600 is illustrated in FIG. 20, including the apparatus 100 as described herein. The system 600 comprises a housing 602 formed of four walls upstanding from a base wall and a top wall parallel to the base wall and spaced apart from it by the length of the walls. The housing 602 forming a chamber 604 with a hinged door 606 in one wall for receiving the apparatus 100 as described herein. On the front panel of the system 600 is a control panel 608 to enable the user to program and control various features positioned within the chamber 604, as well as their interactions with the apparatus 100. The housing 602, which defines an enclosed space, being chamber 604, houses multiple components in which one or more unit operations (i.e., steps) of cell and/or gene therapy manufacturing process can occur.

[0175] FIG. 21 shows a portion 601 of the system 600 with the housing 602 removed for ease of depiction. Inside the housing 602 the portion 601 of the system 600 comprises a linear actuator 610 for compression of a first container in use, a linear actuator 612 for compression a second container, in use, a friction drive mechanism (614, 616, 618) mounted on a mounting plate 620 and operable to rotate the apparatus 100, or a portion thereof. The internal structure of the apparatus is machined from aluminum, the linear actuators 610, 612 are aluminum and steel constructions with the lead screws hard coated in TFE dry lubricant.

[0176] In addition to the mounting plate 620, the mounting bracket comprises a mounting flange (not shown), located above the mounting plate in such a way as to retain the apparatus 100 by frictional fit between the mounting plate 620 and the mounting flange.

[0177] The layout of the linear actuators 610, 612 allows them to be hidden in the rear of the apparatus by a cover (not shown) through which only the plungers 610a, 612a protrude to actuate the relevant container and/or connector. In this embodiment, the plungers 610a, 612a may compress bellow-type containers, specifically the bellows of the auxiliary and primary containers respectively. This helps to give a clean and uncomplicated appearance, and provides an apparatus that is simpler to clean and wipe down. A power supply and the electronics for the actuators and the frictional drive mechanism are mounted on the plate 622 below the mounting plate 620. The four risers 624 are adjustable in height and operable to change the distance between the mounting plate 620 and the plate 622 housing the power supply and the electronics. In this way, the apparatus can accommodation different sizes of primary containers.

[0178] The housing 602 contains all of the actuators and electronics necessary to manipulate the apparatus 100. The plunger 610a and plunger 612a operable to exert a compression force on the respective containers, and/or a suitable connector, with a maximum force of 100N. The motors driving the linear rails are bipolar stepper motors.

[0179] The frictional drive mechanism (614, 616, 618) comprises a drive wheel 614 located on mounting plate 620 and operable to impart rotation on the apparatus 100. The drive wheel 614 is a bipolar stepper motor. The actuator stepper motors on the linear rails and the stepper motor in the frictional drive mechanism are driven by a control system and associated power supply (not shown). The drive wheel 614 may be operable to rotate the body 200, or the cover 300. The drive wheel 614 may engage with a container at the lower surface of the body 200 such that the container and, thus, the body 200, are rotated in use.

[0180] FIG. 22 shows the elements of the frictional drive mechanism (614, 616, 618) mounted to the mounting plate 620 of the mounting bracket. To allow the apparatus 100 and the containers to be inserted from front only, a drive method has been developed where the apparatus 100 may be held between three friction wheels, one of which being driven by drive wheel 614, the other spring loaded 616 and the third being a hinge wheel 618 within the door that opens to allow insertion of the apparatus 100 and closes to lock it in place. The apparatus 100 rotates on low friction PTFE pads 626 on the mounting plate 620. The spring force of the spring-loaded friction wheel 616 will be such that there is no slip between the drive wheel 614 and the outer face of the body 200 or the cover 300 of the apparatus 100. The drive wheel 614 is directly connected to a stepper motor.

[0181] The apparatus 100 may also be fitted, as part of the body 200 or the cover 300, with a series of magnets around its circumference so that its position can be read by a Hall Effect sensor mounted on the mounting plate 620. The apparatus 100 therefore acts like an encoder and gives closed loop position feedback independent of any motor slip. The Hall Effect sensor mounted to the mounting plate 620 attached to the housing 602 is operable to detect the magnetic field from the magnets on the apparatus 100 mounted in the housing 602. The Hall Effect sensor is operable to detect the position of apparatus 100 relative to the mounting plate 620.

[0182] As will be clear to the person skilled in the art, any appropriate container can be used with the apparatus. For example, in place of an aseptic connector 400 there may be provided a container, a vacutainer or the like, and in place of the container 500 there may be provided an aseptic connector, a vacutainer or the like. Any combination of these containers is contemplated herein.