Methods of preparing and using an aseptic mixing system
11364475 ยท 2022-06-21
Assignee
Inventors
Cpc classification
B01F33/86
PERFORMING OPERATIONS; TRANSPORTING
B01F33/453
PERFORMING OPERATIONS; TRANSPORTING
B01F27/0541
PERFORMING OPERATIONS; TRANSPORTING
B01F27/053
PERFORMING OPERATIONS; TRANSPORTING
International classification
B01F33/453
PERFORMING OPERATIONS; TRANSPORTING
B01F27/053
PERFORMING OPERATIONS; TRANSPORTING
B01F27/054
PERFORMING OPERATIONS; TRANSPORTING
Abstract
A mixing system typically for use in a container for mixing its contents, the mixing system including a cap unit, an extension unit and a magnetic mixing unit that is attached to the cap unit by the extension unit. The magnetic mixing unit can be folded to permit insertion and/or removal of the system via a mouth of the container. The extension unit and magnetic mixing unit connect via a hinge formed by upper and lower hinge portions that meet at a pivot point. The hinge portions extend from the pivot point along a first axis. The magnetic mixing unit includes a first magnetic elongate member that extends from the lower hinge portion along a second axis that is substantially perpendicular to the first axis, and a second magnetic elongate member that extends from the lower hinge portion along the second axis in the opposite direction relative to the first elongate member. The magnetic member(s) may be provided by a plastic coated magnetic stir bar.
Claims
1. A method of preparing and using an aseptic mixing system, comprising: providing an aseptic plastic container which when upright has a narrow upper mouth leading to a wider bottom mixing portion; providing a mixer comprising: a cap configured to engage the container upper mouth, the cap and upper mouth being configured to form an aseptic seal and maintain an aseptic environment within the container, an extension shaft having a first end connected to an underside of the cap and extending along a longitudinal axis to a second end, the extension shaft including an aluminum inner reinforcing rod encapsulated in an inert plastic, an upper hinge portion rotatably secured to the second end so that the upper hinge portion may freely rotate about the longitudinal axis, a single mixing bar having a length greater than a width of the upper mouth but less than a width of the wider bottom mixing portion of the container, the mixing bar including a magnetic member encapsulated in an inert plastic and having a specific gravity that will enable the mixing bar to sink in water, and a lower hinge portion secured at a center of the mixing bar so as to divide the mixing bar into first and second elongate members extending in opposite directions, the lower hinge portion being pivotally connected to the upper hinge portion about a lateral pivot axis that is perpendicular to the longitudinal axis, wherein the mixing bar may freely pivot between an insertion position parallel to the longitudinal axis and laterally adjacent to the extension shaft and a deployment position perpendicular to the longitudinal axis and spaced from the second end of the extension shaft, and a tubular lock sleeve axially slidable along the extension shaft between a locked position surrounding the lower hinge portion which prevents the mixing bar from pivoting out of the deployment position and an unlocked position which permits the mixing bar to pivot between the insertion position and the deployment position, sliding the lock sleeve along the extension shaft to the unlocked position, and pivoting the mixing bar to the insertion position, wherein the lower hinge portion prevents the lock sleeve from sliding back to the locked position when the mixing bar is in the insertion position, inserting the mixer through the upper mouth into the container and positioning the container upright so that the mixing bar freely pivots by gravity to the deployment position once past the upper mouth and permits the lock sleeve to drop by gravity to the locked position, engaging the cap onto the container upper mouth to form an aseptic seal and maintain an aseptic environment within the container, adding a bioreactor fluid to the container, rotating the mixing bar about the longitudinal axis the using an external magnetic drive system located outside the container, and culturing cells in the container while rotating the mixing bar.
2. The method of claim 1, wherein the upper mouth has external threads and the cap has internal threads configured to engage the external threads.
3. The method of claim 1, wherein, in the deployment position, the lock sleeve is held upward by a friction fit around the extension unit, and the step of sliding the lock sleeve to the unlocked position includes sliding the lock sleeve upward until it is held by friction around the extension unit, and the method further includes releasing the friction hold of the lock sleeve onto the extension unit prior to the step of inserting the mixing bar through the upper mouth.
4. The method of claim 1, wherein the magnetic member is a neodymium magnet having a nickel coating.
5. The method of claim 1, wherein the inert plastic around both the extension shaft and the mixing bar comprises a gamma stable thermoplastic selected from the group of PVDF, PP, PE and PC, and the specific gravity of the mixing bar is in a range of 1.6 to 2.0.
6. The method of claim 1, further including one or more baffles attached to and extending radially outward from the extension shaft.
7. The method of claim 6, wherein the one or more baffles comprises a single longitudinally-oriented baffle extending laterally away from the extension shaft with a first section and a second section closer to the second end of the extension shaft that is thinner laterally than the first section and spaced from the extension shaft to form a recess configured to receive the lock sleeve when the lock sleeve slides to the unlocked position.
8. The method of claim 1, wherein the mixing bar has a round cross section and the first and second elongate members terminate at rounded ends.
9. The method of claim 1, wherein the mixing bar includes angled plates or fins that extend outward from ends of the first and second elongate members.
10. A method of preparing and using an aseptic mixing system, comprising: providing an aseptic container which when upright has a narrow upper mouth leading to a wider bottom mixing portion; providing a mixer comprising: a cap configured to engage the container upper mouth, the cap and upper mouth being configured to form an aseptic seal and maintain an aseptic environment within the container, an extension shaft having a first end connected to an underside of the cap and extending along a longitudinal axis to a second end, an upper hinge portion rotatably secured to the second end so that the upper hinge portion may freely rotate about the longitudinal axis, a single mixing bar having a length greater than a width of the upper mouth but less than a width of the wider bottom mixing portion of the container, the mixing bar containing a magnet and having a round cross section and terminating at rounded ends, and a lower hinge portion secured at a center of the mixing bar so as to divide the mixing bar into first and second elongate members extending in opposite directions, the lower hinge portion being pivotally connected to the upper hinge portion about a lateral pivot axis that is perpendicular to the longitudinal axis, wherein the mixing bar may freely pivot between an insertion position parallel to the longitudinal axis and laterally adjacent to the extension shaft and a deployment position perpendicular to the longitudinal axis and spaced from the second end of the extension shaft, and a lock sleeve axially slidable along the extension shaft between a locked position which prevents the mixing bar from pivoting out of the deployment position and an unlocked position which permits the mixing bar to pivot between the insertion position and the deployment position, sliding the lock sleeve along the extension shaft to the unlocked position, and pivoting the mixing bar to the insertion position, inserting the mixer through the upper mouth into the container and positioning the container upright so that the mixing bar freely pivots by gravity to the deployment position once past the upper mouth and the lock sleeve drops by gravity to the locked position, engaging the cap onto the container upper mouth to form an aseptic seal and maintain an aseptic environment within the container, adding a bioreactor fluid to the container, rotating the mixing bar about the longitudinal axis the using an external magnetic drive system located outside the container, and culturing cells in the container while rotating the mixing bar.
11. The method of claim 10, wherein the upper mouth has external threads and the cap has internal threads configured to engage the external threads.
12. The method of claim 10, wherein the lock sleeve is tubular and surrounds the lower hinge portion in the locked position which prevents pivoting of the lower hinge portion and thus the mixing bar from pivoting out of the deployment position.
13. The method of claim 12, wherein, in the deployment position, the lock sleeve is held upward by a friction fit around the extension unit, and the step of sliding the lock sleeve to the unlocked position includes sliding the lock sleeve upward until it is held by friction around the extension unit, and the method further includes releasing the friction hold of the lock sleeve onto the extension unit prior to the step of inserting the mixing bar through the upper mouth.
14. The method of claim 10, wherein the magnet is a neodymium magnet having a nickel coating.
15. The method of claim 10, wherein the extension shaft is covered by an inert plastic and the mixing bar is an elongated magnetic bar covered by an inert plastic.
16. The method of claim 15, wherein the inert plastic comprises a gamma stable thermoplastic selected from the group of PVDF, PP, PE and PC, and the specific gravity of the mixing bar is in a range of 1.6 to 2.0.
17. The method of claim 10, further including one or more baffles attached to and extending radially outward from the extension shaft.
18. The method of claim 17, wherein the one or more baffles comprises a single longitudinally-oriented baffle extending laterally away from the extension shaft with a first section and a second section closer to the second end of the extension shaft that is thinner laterally than the first section and spaced from the extension shaft to form a recess configured to receive the lock sleeve when the lock sleeve slides to the unlocked position.
19. The method of claim 10, wherein the step of inserting the mixer through the upper mouth into the container is done with the container at an angle such that the container must be subsequently rotated to an upright position.
20. The method of claim 10, wherein the mixing bar includes angled plates or fins that extend outward from ends of the first and second elongate members.
Description
DESCRIPTION OF THE DRAWINGS
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DETAILED DESCRIPTION
Description in Connection with Figures
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(11) As shown in
(12) The cap unit may include a cap 12 and a cap connector 1 (e.g., a stabilization connector).
(13) The extension unit may include an extension shaft 10 (e.g., a tube), a lock sleeve cap 2, an upper bearing 3, a bearing pin 4, a joint lock 5, a lock sleeve 9, and a baffle 11. The extension unit may attach the mixing unit to a cap unit of the system. In various embodiments, the extension unit has an extension axis that extends between the cap unit and the mix unit parallel to the Z-axis.
(14) A challenge with a movable mixing blade on a pivot is that the blade will tend to wobble. This wobbling will cause too much turbulence during mixing and the magnetic field will decouple causing damage to the process. Therefore, in a most preferred embodiment, there is a stiffener or reinforcing rod, e.g., of aluminum encapsulated within the extension shaft extending the majority of the length of the shaft (see the dashed lines 10a inside extension shaft 10 of
(15) In some embodiments, a lock sleeve may be moved downward to hold the mixing unit at a mixing position to minimize wobbling.
(16) In various embodiments, one or more baffles 11 may be used to alter fluid flow within the container to cause turbulent mixing and to disrupt laminar rotating fluid flow within the container. A baffle 11 may be attached to an extension shaft 10 of the extension unit at one or more sides. One or more baffles 11 may be attached to the sides of the lock sleeve 9.
(17) The mixing unit may include a hinge formed by an upper hinge 6 portion, a lower hinge portion 7, a pivot (e.g., an axle that connects the upper hinge portion 6 and the lower hinge portion 7 that extends along the Y-axis), and a pair of oppositely extending elongate members (e.g., a first elongate member and a second elongate member forming a stir bar 12) that extend from and are fixed to the lower hinge section 7. The mixing unit may include a first mix section that is comprised of the upper hinge portion 6, and a second mix section that is comprised of the lower hinge portion 7, the first elongate member, and the second elongate member.
(18) In some embodiments, the lower hinge portion 7 may hang downward (e.g., away from the cap unit along the Z-axis) at rest such that the oppositely extending first and second elongate members extend horizontally (e.g., when the system is installed in an upright container, along the Y-axis).
(19) In some embodiments, end pieces of the first and second elongate members may be adapted to have angled plates or fins that extend from the ends of the first and second elongate members in the XY plane. The plates or fins may have rectangular, trapezoidal, or other cross sections. (See
Exemplary Operation
(20) Operation in
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(22) Before folding the mixing unit, the lock sleeve 9 may need to be moved toward the cap unit along the extension axis, as shown in the progression between
(23) For insertion into the container, the mixing unit may be rotated at the pivot such that the lower hinge portion 7 extends laterally (e.g., along the X-axis) away from the extension axis of the extension unit, and the elongate members extend parallel to the extension axis (e.g., parallel to the Z-axis), as shown in
(24) In various embodiments, the mixing unit can be held upward at a folded position (e.g., substantially parallel to the extension axis) with one of the user's hands while the other hand holds the cap and inserts the system into the container. (See
(25) The mixing unit can then be inserted and once inside the mouth released. (See
(26) The system may then be further lowered into the container until the cap unit can engage the container opening. (See
(27) Details of
(28) As shown in
(29) The bottom edge of the first section and the innermost edge of the second section in the XZ-plane may be configured to form a receiving section or recess that is configured to receive the lock sleeve 9 when the lock sleeve 9 has been moved along the Z-axis towards the cap unit and away from the pivot. In some embodiments, the second section extends along the Z-axis to a position that is higher than the highest part of the first (or second) elongate member that extends towards the cap unit while at a folded position. (See
(30) At the position shown in
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(32) As shown in
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(35) Detailed Description of Exemplary Components in
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(38) The upper section may have a smaller diameter than the mid-section, which may assist with engagement of the cap connector 1 with the cap 12. The upper section may be sized to be press fit into a corresponding opening of the cap 12.
(39) The lower section may have a diameter that tapers along the Z-axis away from the mid-section to a lower edge. The lower section may be formed with a downward opening cavity sized to receive the extension shaft 10 of the extension unit.
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(42) Alternatively, the lock sleeve and lock sleeve cap make be formed unitarily, e.g., by machining the lock sleeve and cap out of one piece of bar stock.
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(45) The lower section may have a bottom face formed with an opening sized to receive the bearing pin 4. The opening may be part of a shaft that is formed within the upper bearing 3 and that extends along the Z-axis. The bearing pin 4 may be inserted into the shaft in the upper bearing 3 and secured such that the bearing pin 4 can support the weight of the mixing unit, including the upper hinge portion 6, the lower hinge portion 7, and the first and second elongate members. The bearing pin 4 may hold the upper hinge portion 6 against the upper bearing 3.
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(52) The upper hinge portion 6 is further formed with a first projection (its left side proximate the bottom) and a second projection (its right side proximate the bottom) that together define a slot extending in the YZ-plane for receiving the lower hinge portion 7. Each of the first projection and the second projection are formed with a corresponding pivot receiving passage that extends along the X-axis (the circle in
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(57) The second section may be attached to or integrally formed with the first section, and may be formed to receive and conform to the external cylindrical surface of the lower part of the lower hinge portion 7, which may be a cylinder that extends along the Y-axis. The lower boundary of the second section along the Z-axis, when projected along the X-axis into the YZ-plane, may have a rounded shape that corresponds to an arc in the YZ-plane that opens upward along the Z-axis. The projection of the outer boundary of the second section along the Z-axis into the YX-plane may be circular.
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Exemplary Illustrations of the System with Containers
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(69) Although the invention has been described using specific terms, devices, and/or methods, such description is for illustrative purposes of the preferred embodiment(s) only. Changes may be made to the preferred embodiment(s) by those of ordinary skill in the art without departing from the scope of the present invention, which is set forth in the following claims. In addition, it should be understood that aspects of the preferred embodiment(s) generally may be interchanged in whole or in part.