This disclosure relates generally to the fluid handling arts and, more particularly, to containers for handling fluids, systems for handling fluids, and related fluid handling methods.
Fluid handling applications often employ one or more disposable vessels for at least temporarily receiving and containing the fluid during the processing operation. For example, in the course of bioprocessing, sealed containers of flexible plastic film (referred to as “bags” in the vernacular) are often used under sterile conditions for fluid storage, cell culture re-suspension, viral inactivation, final formulation, final fill, and in other areas, including as bioreactors.
Despite the overwhelming acceptance of such containers in the market as being reliable for fluid handling (and particularly in relation to bioprocessing, given the requirement for sterility in many applications and the desire to avoid cleaning/reuse), limitations remain. For one, dealing with fluid-filled flexible bags can be a challenge, as their thin walls and amorphous shape when filled dictates special handling considerations. Separate rigid containers may be used to provide external support, but these containers are typically designed to accommodate only a single size and shape of vessel (such as, for example, a “bag-in-box” type of arrangement, where an inner bag is specially adapted for occupying the entire volume of an outer box). Filling of the vessels often involves guesswork based on visual acuity, which can at best lead to inconsistency, and is virtually impossible when the container is comprised of opaque materials that make accurate visual perception of the fluid level impossible.
Thus, a need is identified for a manner of providing an improved container for use in fluid handling, and bioprocessing in particular. The container would be capable of use in addressing a variety of different requirements for fluid processing operations, including the proper filling of the container, as well as the ability to manipulate and transport it in an easy and efficient manner. Overall, use of the improved container would thus lead to a simplification of the fluid processing operation with improved results and a concomitant reduction in the expense associated with such use.
According to one aspect of the disclosure, an apparatus is provided for receiving an at least partially flexible vessel adapted for receiving a fluid. The apparatus may include an overpack including a base having a floor and an upstanding sidewall forming an interior for receiving the vessel. A partition may be removably positioned in the interior of the overpack. The partition may extend generally transverse to the sidewall and generally aligned with the floor to form a compartment in the interior of the overpack for receiving the vessel. In one embodiment, the base of the overpack includes a door for providing access to an exterior compartment of the base. The overpack may also include at least one hanger for hanging the overpack in an inverted condition, and the base may include the hanger. The door may comprise a pair of hinged flaps, each including at least one opening to form the hanger. The hanger may be integrally formed with the overpack, and may comprise a strap loop.
The overpack may further include an upper wall adapted for receiving a conduit for connecting with the vessel in the overpack. The partition may be adapted for receiving the conduit. The partition may further include an apex formed by a pair of sloped walls adapted for causing fluid to drain from the vessel. The partition may include a generally C-shaped cross-section.
The apparatus may further include a coupler adapted for forming a non-contact coupling with a component in the vessel. The component may comprise, for example, a magnetic agitator. The coupler may, for example, comprise a material for forming a magnetic coupling with the magnetic agitator.
The overpack may comprise a rigid material. Particular materials used may include cardboard, paperboard, plastic, and combinations thereof. The particular material may also be corrugated for added strength.
A retainer may also be provided for removably retaining the partition within the interior compartment of the overpack. At least one receiver may also be provided for receiving a lifting device. In one particular embodiment, the overpack includes a pair of spaced receivers, each adapted for receiving one fork of a bifurcated lifting device.
The overpack may comprise an upper wall formed of two or more mating panels adapted to interlock with each other. The overpack may further include a handle. In one embodiment, the handle comprises at least one opening formed in at least one sidewall of the overpack, the opening adapted for being grasped by a hand of a user. The apparatus may further include a tubing positioned in a space between an upper surface of the partition and a lower surface of an upper wall of the overpack.
The overpack may have a particular cross-sectional shape. For example, the overpack may be generally polygonal in cross-section. Another example is a generally square in cross-section.
The apparatus may further include a carrier adapted for receiving the vessel and for nesting in the interior of the overpack. The carrier may include the partition. The apparatus may further include a support for supporting the partition in at least an inverted condition of the overpack, which may optionally form part of the carrier. In one embodiment, the support comprises at least one upstanding wall extending from the partition to a lower wall of the inverted overpack.
A further aspect of the disclosure relates to an apparatus for receiving an at least partially flexible vessel adapted for receiving a fluid. The apparatus comprises an overpack including an interior for receiving the vessel, and a partition for positioning in the interior of the overpack adjacent to the vessel. The partition may include a taper in a vertical direction for assisting in draining fluid from the vessel when positioned in the interior of the overpack.
In one embodiment, the vessel includes a conduit for receiving fluid. The conduit may pass through the partition into a space between a first surface of the partition and an opposing, second surface of the overpack. The partition may be at least partially above or at least partially below the vessel when in the overpack.
The disclosure also presents as a further aspect an apparatus for receiving an at least partially flexible vessel adapted for receiving a fluid. The apparatus comprises an overpack for receiving the vessel. The overpack may include a hanger for hanging the overpack in an inverted condition. In one embodiment, the overpack is more rigid than the flexible vessel.
Another aspect of this disclosure pertains to an apparatus for handling a fluid. The apparatus comprises an overpack including an interior for receiving the vessel. The overpack includes a base connected to at least one upstanding sidewall. A vessel is provided for positioning in the interior of the overpack, and which vessel includes at least one component. A partition may also be provided for positioning in the interior of the overpack adjacent to the vessel. A coupler for forming a non-contact coupling with the component of the vessel is also provided.
The component may comprise a magnetic impeller. In such case, the coupler may be adapted for forming a magnetic coupling with the magnetic impeller prior to being engaged by a magnetic driver for driving the impeller. The vessel may also comprise a flexible bag, and the overpack may be rigid.
Related aspects of the disclosure pertain to a pallet carrying a plurality of the apparatuses as described above. Furthermore, a filling station may be provided for filling the vessel with the fluid when positioned in the interior of the overpack constructed according to the foregoing description. An assembly may include a bag for containing a plurality of the apparatuses of any of the foregoing disclosure.
A further aspect of this disclosure relates to a system for use in filling a plurality of fluid containers with fluid from a fluid source. The system comprises a first delivery line for simultaneously delivering the fluid to the plurality of containers. A valve is associated with each of the containers for controlling the flow of fluid from the delivery line to the container. A measuring device is also provided for measuring the fluid delivered to at least one of the containers and generating a corresponding output. A controller is also provided for controlling the valve based on the output.
The measuring device may comprise a scale. A scale may also be provided for weighing each of the plurality of containers. The measuring device may comprise a flow meter, a metering pump, or the like.
The first delivery line is associated with a branch line for delivering the fluid to each of the plurality of containers. Each valve may be associated with one branch line. A pump may also be provided for pumping fluid through the first delivery line, and at least one reservoir may be provided for receiving fluid remaining in the first delivery line when the valves are closed. A reservoir may also be connected to the first delivery line for receiving gas purged from the containers. A second delivery line may also be used for delivering a fluid in parallel with the first delivery line.
Related methods are also disclosed. For instance, a method for processing a fluid in a bag-in-box container including at least one port formed in an upper portion thereof is described. The method comprises inverting the bag-in-box container to drain fluid from the at least one port. The method may further include providing the bag-in-box with an at least partially sloped wall when inverted for assisting in draining the fluid through the port. The method may further include the step of using an integral mixer in the bag-in-box container to agitate or resuspend the fluid prior to the step of inverting.
A further method for filling a plurality of vessels is also described. The method comprises simultaneously filling the vessels through a common delivery line associated with a valve for controlling the fluid flow to each vessel, and closing the valve associated with each vessel when a pre-determined condition is reached. The method may further include the step of weighing the vessels, and wherein the pre-determined condition comprises a particular weight.
A further aspect of this disclosure relates to a fluid handling apparatus, comprising a box, a carrier for nesting in the box, and a bag adapted for receiving the fluid and for positioning in the carrier. The carrier may include a sloped wall for assisting in guiding the fluid to a drain of the bag. The sloped wall may comprise an upper wall of the carrier adjacent to an upper wall of the box, which upper wall may include an opening for receiving a port of the bag. The upper wall may also include vertically extending supports for engaging an upper wall of the box when inverted.
The bag may further include a mixer, and a retainer may be provided for retaining the mixer. The retainer may comprise a coupler for forming a non-contact coupling with the mixer. The coupler may be positioned in an exterior compartment of the box spaced from an interior compartment for receiving the bag.
Further to the foregoing disclosure is the provision of an apparatus comprising a bag including a magnetic mixer, an overpack for receiving the bag, and a coupler for forming a magnetic coupling with the magnetic mixer through the overpack. Still further, an apparatus comprising a flexible vessel includes a magnetic mixer, an overpack for receiving the flexible vessel, and a coupler for forming a magnetic coupling with the magnetic mixer through the overpack.
A related method for processing a fluid comprises at least partially filling a bag with the fluid, mixing the fluid using a mixer in the bag, and inverting the bag to dispense the fluid. The filling and dispensing steps may be completed using the same port. The filling and dispensing steps may be completed using different ports on the same port fitment, as well as by using ports connected to a common wall of the bag. The method may further include the step of retaining the mixer to prevent movement relative to the bag prior to the inverting step. The filling step may comprise filling the bag in an overpack, and the inverting step may comprise inverting the bag and the overpack together.
Reference is now made to
A divider or partition 16 is located in the interior of the overpack 12 to form a compartment for receiving the vessel or bag 14, and is generally oriented in a plane parallel to the upper and lower walls 12a, 12c and thus transverse to the sidewall 12b. In one aspect of the disclosure, the partition 16 is removable from the interior compartment of the overpack 12, yet capable of being retained in a particular position (such as adjacent to the upper portion of the bag 14) when the overpack is inverted. This retention may be accomplished by way of an attachment to the overpack 12, such as by using mechanical fasteners R (e.g., clips, screws, bolts, or the like) for connecting to the inner surface of the sidewall(s) 12b. Alternatively, fasteners in the form of adhesives (including tape), hook-and-loop fasteners, magnets, or the like could be used, alone or in combination with other fasteners. Still another alternative, as described in more detail below, is to provide vertically extending supports (such as spacers, blocks, legs, posts, dowels, etc., whether integral or otherwise) for supporting the partition 16 when the overpack 12 is inverted (which supports would engage the lower wall, which it should be appreciated is the upper wall 12a in the non-inverted condition).
Prior to being fixed in place, the partition 16 in the illustrated embodiment may be moved to a desired position along the interior of the overpack 12. This ability for relative movement advantageously allows the container 10 to be used in connection with a variety of shapes and sizes of bags, simply by making the necessary height adjustment. Further, this may allow for reuse of the overpack 12 with a replacement bag (possibly of a different size or shape), once a fluid processing operation is completed.
As shown in
The partition 16 may be arranged to expose any ports 14a associated with the bag 14. This may be done by providing an opening 16a in the partition 16 sized and shaped to accommodate any port fitment. Specifically, the opening 16a may be arranged to allow the fitment base to register therein. This registration may provide an assurance as to the location of the ports 14a, which may be desirable for reasons that will be understood upon reviewing the following disclosure.
As mentioned previously,
The flap or flaps, when present, should allow for the passage of the fluid, such as through the conduit 18, even when closed. This may be accomplished by providing an opening O for this purpose (which may be in any one flap, or between multiple flaps). Alternatively, this opening may be provided in the sidewall 12b or lower wall 12c of the overpack 12, if necessary or desired for a particular operation. Likewise, there could be one or more openings in more than one of these walls 12a, 12b, 12c, as necessary or desired.
Another aspect of the disclosure relates to the ability to recover the fluid from the bag 14 by inverting it, as shown in
To facilitate use in an inverted condition, the overpack 12 may be provided with one or more hangers. For example, as shown in
In this condition, the aligned openings 20a forming the hangers may readily receive a support structure for supporting the entire container 10 in the inverted condition. For instance, the structure for positioning in the openings 20a may comprise the bifurcated components, such as forks F, of a lifting device D. This lifting device D may be static, as shown in
In some instances, the bag 14 may include a component used during the fluid processing operation, such as for example a magnetic agitator 22 for agitating the fluid as the result of a non-contact coupling with an external motive device (which avoids the need to dynamic seals and shafts and thus helps to maintain the sterile condition of the interior compartment of the bag, when such is desired for a particular processing regimen). Such a magnetic agitator 22 may be retained against lateral movement by a post 22a (as described in detail in U.S. Pat. No. 7,481,572, the disclosure of which is incorporated herein by reference), but may be allowed to move along the post in the vertical direction (note arrow V) in order to accommodate the formation of a non-contact (e.g., magnetic) coupling with an external motive device (not shown).
To prevent such movement prior to use or after inversion, and thus reduce the risk of potential perforation should the walls of the bag come into contact with any part of the agitator 22 (such as the blades typically included), a retainer in the form of an external coupler 24 may be provided for forming a non-contact (again, possibly magnetic) coupling with the agitator 22. In one embodiment, this coupler 24 may be a thin, disc-shaped structure formed of a magnetic material, and may include a central opening for receiving any locator projection (not shown) for ensuring proper alignment.
As shown in
It should also be appreciated that the inclusion of the mixer in the vessel (bag 14) allows for the single container 10 to be used for filling, processing, and then dispensing. Indeed, in cases where the fluid is not homogenized during filling, or when time has passed since filling such that the fluid has perhaps separated or settling has occurred, the mixer may advantageously be used for agitation and re-suspension prior to dispensing the fluid.
The container 10 may also be adapted to allow for easy manual lifting in either the inverted or non-inverted condition. Turning to
Turning back to
With continued reference to
Turning to
With further reference to
Each branch line 106 may connect with the free end of the conduit 18 of each container 10 for which filling is desired (possibly with a suitable relief valve to allow air to escape the vessel during filling), or may be connected directly to the port 14 of the flexible vessel, as shown. Each branch line 106 is also associated with a valve, such as a pinch valve 108 (e.g., ACRO Model 284 or Model 958), for controlling the fluid flow. Accordingly, by opening the valves and pumping the fluid through the delivery line 104, it flows through the branch lines 106 and ultimately to the containers 10. Once filled to the desired level, the delivery may be halted by closing the valve 108. The filled container 10 may be removed from the system 100 for later use, such as by being palletized as previously described and shown in
In many instances, the filling of the vessels of each container 10 may not proceed at the same level due to various factors, such as flow rates, pressure, folds, and the like. Rather than having an operator visually monitor the filling operation or use level sensors, which may lead to inconsistent results in the event the bag 14 becomes folded in the overpack 12 prior to or during filling, the filling operation may be automated by associating each valve with a control system that controls the valve in order to regulate the fluid flow. As an example, each container 10 may be associated with a scale 110 for weighing the container 10 and fluid F. Using feedback, such as an output signal from a controller (see
Once filling is complete, the bag 14 or vessel of each container 14 may be sealed. This may be done using an aseptic tube sealing system for sealing the conduit 18, such as a QUICKSEAL device. Alternatively, a fitting may be provided on the conduit 18, including possibly one incorporating a sterile filter.
Still referencing
An upstream pump, such as a peristaltic pump 114, may be used to control the flow to this bag 112, such as by opening to allow gas to pass and then closing before fluid is introduced to the delivery line 104. An associated valve 116 (e.g., a PENDOTECH throttling pinch valve) may be used to close delivery line 104 and thus prevent any flow from returning to the source, such as tank 102.
Likewise, once filling is complete, fluid remaining in the line 104 must be purged. A second reservoir, such as a bag 118, may be provided adjacent to the end of the line 104, and may also be associated with a valve, such as a pinch valve 120. This valve 120 is normally closed during the initial purge and filling operation, but then opened when the valves 108 and 116 are closed. The peristaltic pump 114 may then be used to force the remaining fluid to flow into the bag 118 serving as the second reservoir.
With reference again to
A second embodiment of the container 10 is also disclosed, with reference to
As mentioned above, it should be appreciated that the extensions 17d (whether in the form shown or otherwise, such as for example Styrofoam blocks adhered in place) may be used in connection with other embodiments, such as the embodiment of
An optional step of assembly may be to retain the port 14a of the vessel or bag 14 relative to the carrier 17. As shown in
Turning now to
As mentioned above, the bag 14 is typically formed of one or more layers of thin polymer film, such as polypropylene or polyethelyene. As contrasted with this flexible film, the overpack 12 may be constructed of considerably more rigid materials, such as cardboard, paperboard, plastic, and combinations thereof (with a preference for lightweight materials that can withstand multiple uses and ultimately be recycled). The materials of the overpack 12 may also be reinforced or corrugated for added strength and crush resistance. However, it is also possible to form the overpack 12 of metal in order to provide a more robust container 10, but with corresponding limitations in terms of cost and weight.
As also shown in
Turning back to
The foregoing descriptions of several embodiments made according to the disclosure of certain inventive principles herein are presented for purposes of illustration and description. The embodiments described are not intended to be exhaustive or to limit the invention to the precise form disclosed and, in fact, any combination of the components of the disclosed embodiments is contemplated. The term “flexible” as used herein in the context of the vessel refers to a structure of the vessel that, in the absence of auxiliary support, may conform to the shape of the fluid contained in the vessel, as contrasted with a “rigid” structure, which retains a pre-determined shape when the fluid is present in the vessel. Modifications or variations are possible in light of the above teachings. For instance, measuring of the fluid into the vessels may be achieved using flow meters or a diaphragm pump associated with the branch lines. The wall of the carrier 17 serving as the partition 16 may also be made adjustable such that the carrier may be adapted to accommodate different sizes of bags. The embodiments described were chosen to provide the best illustration of the principles of the invention and its practical application to thereby enable one of ordinary skill in the art to utilize the invention in various embodiments and with various modifications as are suited to the particular use contemplated. All such modifications and variations are within the scope of the invention when interpreted in accordance with the breadth to which it is fairly, legally, and equitably entitled.
This application claims the benefit of U.S. Provisional Patent Application Ser. No. 61/648,986, the disclosure of which is incorporated herein by reference.
Filing Document | Filing Date | Country | Kind |
---|---|---|---|
PCT/EP2013/060342 | 5/20/2013 | WO | 00 |
Publishing Document | Publishing Date | Country | Kind |
---|---|---|---|
WO2013/171340 | 11/21/2013 | WO | A |
Number | Name | Date | Kind |
---|---|---|---|
1647581 | Redemski | Nov 1927 | A |
2807402 | Nelbach | Sep 1957 | A |
4623075 | Riley | Nov 1986 | A |
4968624 | Bacehowski et al. | Nov 1990 | A |
20030183650 | Muise | Oct 2003 | A1 |
20050002274 | Terentiev | Jan 2005 | A1 |
20050173439 | Chen | Aug 2005 | A1 |
20060180643 | Stephenson | Aug 2006 | A1 |
20100102112 | Ouillette | Apr 2010 | A1 |
Number | Date | Country |
---|---|---|
2686321 | Jul 1993 | FR |
JU05-068872 | Sep 1993 | JP |
JU7-11570 | Feb 1995 | JP |
2003-072842 | Mar 2003 | JP |
2003-095249 | Apr 2003 | JP |
2006096510 | Sep 2006 | WO |
2007072522 | Jun 2007 | WO |
Entry |
---|
Merriam-Webster.com (accessed Oct. 4, 2019). |
Number | Date | Country | |
---|---|---|---|
20150151892 A1 | Jun 2015 | US |
Number | Date | Country | |
---|---|---|---|
61648986 | May 2012 | US |