The present invention relates to an apparatus for mixing the contents of a container.
Generally, when bioprocess or pharmaceutical companies want to blend materials to produce a specific material they utilize a mixing container, such as a steel tank mixer or a disposable mixing system. These disposable systems, or single use devices are preferred over stainless steel tanks with their inherent high labor and materials cost for cleaning, because considerable savings in operating and capital cost. The use of single-use devices also minimizes the risk of product carryover and cross-contamination.
However, there are several problems associated with current disposable mixing systems. First, a major problem with developing a disposable mixing system is the manufacturing of a reliable aseptic seal that is inexpensive enough to be discarded after just one use, such as a mixing device that utilizes a low cost plastic bushing seals with a rotating propeller shaft. These seals cannot be relied upon to provide aseptic operation essential for pharmaceutical operations. The cost of such bags with their complex internals is too high for mixer applications, and most of their utility is in high performance applications such as fermentation and cell culture where their high cost can be justified.
Next, magnetically coupled seals offer an alternative to the bushing seals, such as a mixing device with a stir bar placed in a plastic bag that is driven by an external magnetic drive. The advantage of this method is that the fluid inside the mixing bag is completely isolated from the drive. The disadvantage is that, due to economic concerns, the stir bar is very small compared to the container diameter, and consequently performs poorly as a mixer. Since the stirrer is situated at the bottom of the bag, most of the fluid circulation induced by the stir bar fails to get to the upper regions of the mixing bag. The amount of power that can be transmitted through the magnetic coupling is limited. Some efforts have been made to use superconducting magnets to improve the power transmission efficiency, but these are costly to operate, and require liquid nitrogen to maintain the superconducting operation. Scaling up disposable magnetically coupled mixers is quite difficult and the utilization of commercial systems over 100 liters is unlikely. In addition, the stir bar is typically discarded after a single use that leads to a high cost of disposables and a problem with environmental disposal of the rare-earth magnets used in such applications.
A number of attempts have been made to develop a sealless disposable mixer, such as a mixing bag with an oscillating disk mounted at the bottom. The disk is forced to oscillate in the vertical dimension and its movement induces a circulation flow. This device has failed to find any significant commercial application because the fluid motion rapidly diminishes towards the upper regions of the container. The mixing performance is even poorer if the liquid phase has a high viscosity. The problem is that the mechanism constrains the vertical motion of the disk. Thus despite the relatively large diameter of the disk, the amount of fluid moved every oscillation is too small for it to function as an effective mixer.
Next, there is a mixer with multiple mixing platforms in a bag with a vertical shaft with horizontal mixer platforms. The shaft is moved up and down to mix the contents of the bag. The shaft is fixed to the upper surface of the bag that eliminates the need for a rotary seal, but the maximum possible stroke length is small due to the maximum allowable deflection of the top surface. This leads to poor mixing performance. In addition, bulk of the liquid flow bypasses the mixer platforms along the side walls, also reducing mixer efficiency.
Therefore, there is a need for an apparatus that provides the user with a mixing system that has a good mixing performance and is efficient. Also, there is a need for a mixing system that preserves its hermetic integrity and does not require any type of seal.
The present invention has been accomplished in view of the above-mentioned technical background, and it is an object of the present invention to provide an apparatus that has good mixing performance and can be manufactured at a low cost.
In a preferred embodiment of the invention, an apparatus for mixing materials is disclosed. The apparatus includes a support. A mixing container is disposed in the support, where the mixing container is configured to retain materials. A driver assembly is configured to protrude through the support and into the mixing container. The mixing container includes a paddle, the driver assembly is configured to be attached to the paddle, wherein the driver assembly is configured to oscillate the paddle in a back and forth direction at a set angle in order to mix the materials in the mixing container.
In another preferred embodiment of the invention, a mixing device is disclosed, which includes a support. A mixing container is disposed in the support, where the mixing container is configured to retain materials. The mixing container includes a mixing bag and a sleeve, where the sleeve is disposed inside the mixing bag. A driver assembly is configured to protrude through the support into the sleeve. A paddle is inside the sleeve, where the sleeve is configured to isolate the paddle from an environment outside of the mixing bag. The paddle may extend vertically 5% to 95% of a vertical height of the mixing container. The driver assembly is configured to oscillate the paddle in a back and forth direction at a set angle in order to mix the materials in the mixing container.
These and other advantages of the present invention will become more apparent as the following description is read in conjunction with the accompanying drawings, wherein:
The presently preferred embodiments of the invention are described with reference to the drawings, where like components are identified with the same numerals. The descriptions of the preferred embodiments are exemplary and are not intended to limit the scope of the invention.
The present mixing assembly relates to mixing the contents of materials in containers that enable the user to mix components, mix and suspended solids in a single-use disposable format that eliminates cleaning, and reduces contamination. The mixing apparatus overcomes all the prior art limitations by 1) not having any contamination-prone rotating seals; 2) providing a very low cost container without any expensive magnetic stir bars or impellers; 3) providing a container that can be cheaply constructed from a variety of available materials; 4) is scalable in general to large volumes (up to at least 10,000 liters); and 5) requires only a low cost mixing support and a simple rotary mechanical drive assembly. The present apparatus utilizes a novel container with an internal mixing paddle that is oscillated, resulting in a low cost, yet very efficient mixing device.
The present apparatus encompasses a method for mixing ingredients inside a sealed plastic bag, which is a very important application in the bioprocess and pharmaceutical industry. The apparatus is suitable for applications requiring clean operation and the single-use design prevents cross-contamination and product carryover often encountered with poorly cleaned mixing tanks The apparatus may be operated in an open top configuration for ease of component addition. It can also be manufactured in a completely closed configuration with all additions being made through ports in applications requiring such safeguards. The apparatus can be provided pre-sterilized by gamma radiation for applications requiring a sterile mixing vessel. The present apparatus eliminates the need for a rotary seal.
The support 12 may be a tank or barrel molded from polymeric materials. In alternative embodiments, support 12 can be comprised of metal, fiberglass, composites, plastics or any other desired material. While the support 12 is shown as a substantially cylindrical configuration, in alternate embodiments, support 12 may have a polygonal, elliptical, irregular or any other desired shape.
In an embodiment of the invention, driver assembly 40 also includes a typical electric servo motor 48 coupled mechanically to a typical gearbox 46, which in turn is coupled mechanically to a first end of the drive shaft 44. Driver assembly 40 acts as a typical servo motor amplifier that is controlled by a computer, which is able to control the motion of the shaft 44 to start and stop, such as utilizing the electric servo motor 48 and the typical gearbox 46 to instruct the shaft 44 to move 4000-8000 steps per second. In other embodiment of the invention, the electric servo motor 48 and/or gearbox 46 may be replaced with various mechanisms such as gears, cams, pneumatic pistons, hydraulic pistons or other devices that would generate the required oscillating motion. Clamp 42 is attached to a second end of the drive shaft 44. The driver assembly 40 is attached to frame 60 such that only shaft 44 and clamp 42 can rotate a paddle 18 about the vertical axis or the longitudinal axis of the mixing container 16. The driver assembly 40 rotates, drives or oscillates the paddle 18 in one direction through a preset angle and then reverses direction to rotate back to the starting position, and then continue through a set angle that has a range of 1 to 360 degrees in either direction. Once actuated, this cycling or oscillation motion repeats automatically. Various mechanisms such as gears, cams, pneumatic pistons and other devices in place of drive electric servo motor 48 and/or gearbox 46 can be used to generate the required oscillating motion. Also, the drive assembly 40 may be independent of the frame 60. The driver assembly 40 is located under the mixing device 10, which leaves the entire top free for ports 25 (
Referring to
A driver assembly 40 is utilized to move the paddle 18 inside the mixing container 16 and is mounted to the closed end 101,103 of the sleeve 20. The driver assembly 40 moves the paddle 18 in an oscillating motion to mix materials in the mixing container 16. Ports 22, 25 and 23 can be provided on the mixing bag 21. The mixing container 16 is placed inside support 12 such that the sleeve 20 slides over clamp 42 and drive shaft 44. Paddle 18 disposed within mixing container 16 fits into clamp 42 such that the sleeve 20 and the paddle 18 follow the rotation of drive shaft 44.
Unlike conventional mixers that rotate continuously in one direction, the present mixing device 10 has a paddle 18 that oscillates about the longitudinal axis of the mixing container 16. The paddle 18 is isolated from the outside environment of the mixing bag 21 by the flexible sleeve 20, where the sleeve 20 is inside the mixing container 16. The sleeve 20 may be made of a multi-layer material that has anywhere from 1-10 layers. Preferably, the sleeve 20 is made of 1-3 ply material. The material utilized to make the sleeve 20 may be made of a coated nylon, a siliconized coated material, polyethylene, silicone, molded structure, a splyrene structure or spiral structure. The paddle 18 is driven by the drive shaft 44 (
Referring to
The paddle 18 can be manufactured to extend to the entire height of the mixing container 10 thereby providing good mixing regardless of fill volume. The paddle 18 is typically a simple sheet of thermoformed flat plastic that can be made very inexpensively. Also, the paddle 18 may be made of a material such as acrylic, polypropylene, polyethylene, Acrylonitrile butadiene styrene (ABS) or any non-bioinert material. The flat paddle 18 design allows the mixing bag 21 to be packaged flat, reducing storage space and facilitating eventual disposal.
There are no potentially environmentally harmful magnetic stirrers or metal bearings used in the construction of the single use mixing container 16 making disposal of it easy. Scaling up of the mixing device 10 is simple, either by increasing the bag diameter to increase operating volume, or by increasing the height. Maintaining constant tip speed on scale up provides comparable performance at different volumes. The mixing device 10 is very compact with the footprint of a typical mixing tank. For large volumes, multiple sleeves 20, paddles 18 and driver assembly 40 can also be installed in the mixing container 10 (
Since only the flexible sleeve 20, and not the mixing container 16, moves during operation, the mixing container 16 can be manufactured from a wide variety of materials, including multilayer and gas barrier films. This greatly increases the number of potentially usable films. The flexible sleeve 20, as stated above, can be made from a number of available materials based on compatibility and desired operating life.
The cross-sectional view of the complete mixing device is shown in
Referring to
Referring to
The shaft 44 has a much narrower diameter than the sleeve 20, so that as the sleeve 20 twists, its diameter is allowed to shrink down to a size equivalent to the outer diameter of driver shaft 44. An elastomeric coupling 41 can be provided in clamp 42 to allow the sleeve 20 to expand and contract slightly during the twisting operation. This greatly reduces the axial stress on isolation sleeve 20 as it twists. This mechanism does not require a rotary seal as a complete rotation never occurs.
The material of construction of the sleeve 20 must be chosen so that it is resistant to flexing and twisting. For the preferred embodiment of the invention, the sleeve 20 is made of a special formulation of polyethylene (ARMORFLEX®, obtained from ILC Dover, Del.). In another embodiment of the invention, the sleeve 20 may be made from materials, including coated fabrics nylon, polyvinyl and TEFLON®. The speed, acceleration rate, and angle of rotation can all be varied to optimize process performance, such as any angle of rotation in a range between 1 to 360 degrees in either direction. In the preferred embodiment, the best angle for the rotation of the sleeve 20 is 180 degrees in either direction and speeds ranging from 10 to 60 cycles per minute (cpm). Preferably, the sleeve 20 rotates at a speed of 10-30 cpm. The acceleration rate should be 10-300 revolutions per second2 (rps2). Preferably, the acceleration rate is 50 rps2.
Referring to
Referring to
Ports 22, 23 and 25 can be attached to mixing bag 21 during fabrication and are used to introduce materials, sample, and harvest products from mixing container 16. Ports may also be used to introduce typical sensors, such as required for measuring conductivity, pH level, temperature, ionic measurement, non-ionic measurement, non-conductivity, pressures, other types of measurements and oxygen into the mixing apparatus 10. These measurements are often required during mixing to determine homogeneity or to meter in ingredients. Such ports can be placed on the top, bottom, and sides of mixing bag 21. The ports are located to align with cutouts 34 and 36 on the support 12 shown in
Referring to
In one embodiment shown in
In the preferred embodiment, paddle 18 is a flat rigid plastic sheet cut in the shape of a letter H (
The paddle 18 may extend vertically from 5% to 95% of the vertical height of the mixing container 16. Also, the outer diameter of the path of the paddle 18 may be from 25% to 95% of the inner diameter of the mixing container 16.
For applications requiring gas dispersion during mixing, such as fermentation or cell culture, an aeration device can be easily incorporated into mixing apparatus 10. In one embodiment shown in
Another embodiment is shown in
Another embodiment is shown in
The paddle 18 may include hinged panels that extend during rotation in one direction and retracts in the other direction, as shown in
If stirring only in one direction is required, a transmission can be provided to convert the oscillating movement of the drive shaft to a single direction movement of the paddle 18. As shown in
This invention provides an apparatus that allows a user to simply and efficiently mix materials in a disposable mixing system. The user is able to insert media into a mixing bag assembly of the disposable mixing system, where he is able to mix the media by using a driver assembly. The driver assembly is coupled to a paddle that oscillates back in forth at a particular angle to mix the contents of the media in an efficient manner. Thus, this invention provides the user with a disposable mixing system that yields a good mixing performance and is efficient.
Although the present invention has been described above in terms of specific embodiments, many modification and variations of this invention can be made as will be obvious to those skilled in the art, without departing from its spirit and scope as set forth in the following claims.
This application is a filing under 35 U.S.C. 371 and claims priority to international patent application number PCT/US2008/065479 filed Jun. 2, 2008, published on Dec. 11, 2008, as WO 2008/151105, which claims priority to U.S. provisional patent application No. 60/941,766 filed Jun. 4, 2007; the entire disclosure of which is incorporated herein by reference in its entirety.
Filing Document | Filing Date | Country | Kind | 371c Date |
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PCT/US08/65479 | 6/2/2008 | WO | 00 | 11/17/2009 |
Number | Date | Country | |
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60941766 | Jun 2007 | US |