Field of the Invention
The present invention relates to a mixing system, and in particular to a magnetic mixing system and method.
Description of the Related Art
In the preparation of liquid components for biotech and pharmaceutical processing, it is important to perform mixing within a closed environment. The process of manufacturing a biological is very delicate and can fail due to a breach within a closed system because of bacterial or viral ingress. In many instances, certain chemicals must be blended into liquid to form a component of the process or must be continuously stirred in order to inhibit separation during the process. The process is controlled at every step to assure a constant temperature, balanced PH, and foreign substances stay out of the process. For example, it would be undesirable to have heat from a motor disrupting the process. It would also be undesirable to have a large opening in the system, and it would certainly be undesirable to stick one's hand, fingers or other foreign objects into or proximate the process or system. Further, undue shear or vibration will adversely affect the integrity of the system.
Some applications of a magnetic stirrer may be in a perfusion vessel or an aseptic separator device. Other uses may exist.
Long ago, i.e., at least as early as 1917, a magnetic stirrer was proposed by Stringham in U.S. Pat. No. 1,242,493, and later in 1942 improved by Rosinger in U.S. Pat. No. 2,350,534. The stifling element consisted of a rod shaped magnet inside and a neutral shell or covering around it. The magnet that caused the stirring element to rotate was U-shaped and had the poles pointing upward, and was rotatably mounted around a vertical axis, coinciding with a central point on the stirrer. The stirrer rod was simply dropped in the container, and allowed to sit on the bottom of the container.
However, it is much better to suspend the stirrer so that it does not touch the walls or bottom of the container. Touching the bottom or walls can subject the process to a grinding action, which is undesirable and can also serve to produce particulates. Similarly, creation of shear can be problematic for the cells within the process as well. Suspension also eliminates the need for lubrication, which can contaminate the culture. Accordingly, in U.S. Pat. No. 3,572,651 to Harker, the stir bar is suspended.
The controls for the stirrer and the driving force (a magnetic field) may be outside the container in which the cell culture or process is located. Since the stifling force is magnetic, no physical connection of the stir bar and the power source are required. Therefore, the container may be properly sealed and free from contaminants to maintain an aseptic environment.
In some conventional systems, a rod shaped internal magnet is placed within a container holding a fluid to be mixed. The rod shaped magnet may be free to roam across the bottom of the container, and may be coated with PTFE. The rod shaped internal magnet may be engaged by an external magnet located below the container and driven to rotate around an axis perpendicular to a longitudinal axis.
The conventional system may allow friction to occur between the internal magnet and an interior surface of the container when the internal magnet rests on an interior surface of the container and is driven to rotate by the external magnet. As a result, debris from the internal magnet may be released such as during irradiation of the mixer for decontamination. For example, the PTFE may begin to break down during irradiation, allowing the coating to crack and shed particles. In addition, the breakdown of the PTFE coating may allow the internal magnet to rust, which may result in additional particle shedding from both the rusting magnet.
In addition, getting the stirring device into the container without damaging the device or container and without contaminating the system can be a challenge. Because the stir bar extends horizontally (normal to the rod holding it), it can be difficult to get a large enough bar to effectively cause mixing inside the container.
The present mixing system may be useful in many ways, such as in aseptic mixing applications for cell culturing or other applications,
The conventional system may have other drawbacks as well.
Embodiments of the system may permit an oversized mixer to be installed in a container that otherwise would not fit through the neck opening (mouth) of a container, i.e., where the length of the stir bar is greater than the diameter of the mouth of the container. By being suspended from above, the mixing system prevents contact between the mixing system and the interior surface of the container during operation. In various embodiments, the system includes components so that the mixing blade is in an insertion position (substantially normal to its operative position) to minimize the footprint of the apparatus and permit insertion thereof into the container, even if the container has a narrow mouth. The components including the mixing blade may then be dropped into place into its operative, mixing position substantially normal to the insertion position, preferably by gravity. Accordingly, the mixing blade will then be free to rotate around a vertical axis when being driven by an external magnetic force.
One or more components of the system, such as the exterior of the stir bar, may be made from Polyvinylidene fluoride (PVDF). The specific gravity of the stir bar is most preferably 1.78 or about 1.78, or at least preferably between (or from) 1.6 and (or to) 2.0, or about 1.6 to about 2.0. Accordingly, the stir bar will sink in water. Other potential materials may include gamma radiation stable Polycarbonate (PC), Polypropylene (PP), and LDPE Low density Polyethylene. Each of these materials may resist gamma radiation, which may allow the system to be irradiated without substantial degradation of structural integrity. The system may therefore provide better mixing with a reduced likelihood of shedding particles that are mixed into the system.
In some preferred embodiments, the mixing system includes neodymium magnets, which may have a nickel coating. These magnets may have stronger magnetic fields which may allow greater separation between an interior magnet and an external driving magnet, which may result in different mixing effects. In addition or alternatively, the neodymium magnet may have advantages with respect to faster mixing and/or faster response times to changes in speed and/or direction of the external magnet.
Use of a nickel coating may provide advantages with respect to resistance to rust, impact, or cutting in the event that the external coating (e.g., PVDF, PC, PP, LDPE) is damaged or partially removed.
Description in Connection with Figures
As shown in
The cap unit may include a cap 12 and a cap connector 1 (e.g., a stabilization connector).
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.
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
In some embodiments, a lock sleeve may be moved downward to hold the mixing unit at a mixing position to minimize wobbling.
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.
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.
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).
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
Operation in
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 P1 and P3.
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 at P4 of
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 Q4 of
The mixing unit can then be inserted and once inside the mouth released. (See Q5 of
The system may then be further lowered into the container until the cap unit can engage the container opening. (See Q5-Q7 of
Details of
As shown in
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 Q4 of
At the position shown in
As shown in
As shown in
Detailed Description of Exemplary Components in
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.
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.
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.
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.
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
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.
Exemplary Illustrations of the System with Containers
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.
This application claims priority from U.S. Provisional Patent Application Ser. No. 61/954,465 filed Mar. 17, 2014, and which is incorporated by reference herein.
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