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  Bioreactor and methodUSPTO Application #: 20080032396Title: Bioreactor and method Abstract: The bioreactor is for use in performing biological and/or biochemical reactions and includes a vessel, an agitator, a reaction assembly, and a harvesting outlet. The vessel of the bioreactor includes several ports including a mixing port, a reaction port, and a harvesting port. The agitator extends through the mixing port into the vessel while the harvesting outlet extends through the harvesting port and permits the withdrawal of reaction medium to another vessel. The reaction assembly extends through the reaction port into the vessel and has multiple components including a gas conduit adapted to introduce gas into a reaction medium in the vessel, a sampling device adapted to remove a portion of the reaction medium from the vessel without contamination of the remaining reaction medium, and an introduction conduit permitting the introduction of at least the reaction medium into the vessel. (end of abstract)
Agent: David W. Highet, Vp And ChiefIPCounsel Becton, Dickinson And Company - Franklin Lakes, NJ, US Inventor: Bunkim Chokshi USPTO Applicaton #: 20080032396 - Class: 4352941 (USPTO) The Patent Description & Claims data below is from USPTO Patent Application 20080032396. Brief Patent Description - Full Patent Description - Patent Application Claims
BACKGROUND OF THE INVENTION [0001]1. Field of the Invention [0002]The present invention relates to bioreactors for performing biological and/or biochemical reactions. More specifically, the present invention relates to a bioreactor for culturing cells (e.g., biological samples) and for use in the production of medical materials such as hormones, enzymes, antibodies, vaccines, and drugs. The invention further relates to an improved bioreactor that is easy to assemble and maintains sterility throughout the culturing/fermentation operation, and provides for sterile transfer of material to larger vessels. [0003]2. Description of Related Art [0004]In the medical field, it is often necessary to cultivate biological samples for further study of cell structures. Such culturing is often carried out in a bioreactor, which is essentially a sterile vessel that provides internal sealed conditions suitable for cell growth. Bioreactors are also used in the production of medical materials such as hormones, enzymes, antibodies, vaccines, and drugs. Typically, the bioreactor produces batch quantities of the desired material to "seed" larger vessels for further processing. These larger vessels are essentially large bioreactors, which continue the culturing/production process. The "smaller" bioreactors are used to produce an effective amount of material of sufficient concentration such that the material can continue culturing/fermentation in the larger vessel. The larger bioreactor vessels have the increased capacity necessary to produce increased quantities of the desired material for study purposes or for further processing into a final product such as a vaccine or drug. The smaller bioreactors, which feed larger vessels, are limited in production capability because, for a given amount of reaction medium introduced into the smaller bioreactor, the bioreactor can generate only a finite amount of product. As a result, transfer of a "seed" product to a larger vessel is necessary for further production. [0005]Generally, three basic types of bioreactors are used in the medical field for producing biological and/or biochemical reactions, namely, a stationary type, a shaking type, and a rotating type. In stationary bioreactors, a fixedly settled reaction vessel, such as an Erlenmeyer flask, is employed in which a stirrer is provided and which operates to produce a generally horizontal rotary movement to cause agitation of the reaction mixture. This stirring action increases the heat transfer and oxygen transfer rate. While this type of bioreactor permits economical running of reactions, it typically cannot operate with a highly viscous substrate due to insufficient driving torque of the stirrer, and the heat and oxygen transfer are mass transfer limited. In this type of bioreactor, substrates with densities different from that of the solvent, (i.e., the reaction medium), tend to float up or settle down which causes separation of the reaction mixture. [0006]In shaking type bioreactors, a shaking culture using test tubes as the culture vessel has been widely used in the medical field. In this type of system, the reaction is accelerated by reciprocating horizontal movement of the culture vessel. This type of bioreactor also does not operate well with highly viscous mediums and also suffers the same mass transfer and separation problems as the stationary type bioreactor discussed previously. [0007]Rotating type bioreactors are most commonly used in the medical field. In rotating bioreactors, the reaction medium is subjected to agitation by a rotating apparatus inserted into the vessel. An example of a rotating bioreactor is disclosed in U.S. Pat. No. 5,587,298 to Horigane et al. This patent discloses a bioreactor comprised of a reaction vessel defining a reaction chamber which is surrounded by a water jacket for maintaining a predetermined constant temperature. The reaction chamber is provided in the vicinity of the inner wall surface of the reaction vessel. A pair of upright screws is disposed in a side-by-side and adjoining relationship and is used to agitate the reaction mixture. In particular, each screw has a screw thread or a helical fin which engages the corresponding screw thread on the adjacent screw to introduce agitation into the reaction mixture. The reaction mixture is subjected to uniform agitation and to a milling and sieving action in the area where the screw threads are engaged. [0008]Another example of a rotating bioreactor is disclosed in U.S. Pat. No. 4,636,675 to Freedman et al. This patent discloses, in particular, an improved agitator for a bioreactor vessel. The agitator includes a hollow body assembly having an open end and a closed end and a tubular structure communicating with the hollow body assembly at a location spaced from the open end. The tubular structure has an exit opening oriented such that rotational movement of the agitator and the tubular structure causes a suction or draft at the exit opening to cause flow of fluid from the open end of the hollow body assembly through the hollow body assembly and out through the tubular structure exit opening. The agitator is driven by a magnetic drive motor. [0009]Another important aspect of bioreactor systems is the ability to introduce oxygen or other gases to the cell cultures to assist in cell growth to increase the oxygen transfer rate. Aeration of a cell culture or reaction medium is typically achieved by conventional means such as bubbling gases through the fluid by placing a delivery tube in the fluid with an exit near the bottom thereof. However, bubbling air or other gases into cell cultures in this manner can damage the cultures and it is advantageous to minimize bubble size to reduce possible damage to the culture. Typically, a sparger is used to reduce bubble size and is located at the end of the delivery tube. One example of a sparger for use in a bioreactor is disclosed by U.S. Pat. No. 4,727,040 to Freedman et al. This patent discloses a sparger, which includes a narrow, vertically extending outer chamber defined by a solid wall and a wall formed from a screen. Air or other gas is then forced under pressure through a tube to the bottom of the outer chamber and from there to a distribution member having apertures distributed along the lower region of the outer chamber for the release of the gas upwardly into the chamber. The top of the outer chamber is provided with exit openings which communicate to a point above the surface of the medium. The gas bubbles pass through the column of fluid in the outer chamber, a portion which passes through the screen in the form of fine bubbles to reduce bubble size. [0010]With the foregoing background in mind, there is room for improvement in bioreactor design and construction particularly in the area of bioreactor assembly, operation, and the ability to transfer contents to larger reaction vessels in a sterile manner for further processing. SUMMARY OF THE INVENTION [0011]The bioreactor is intended for use in performing biological and/or biochemical reactions and includes a vessel, an agitator, a reaction assembly, and a harvesting outlet. The vessel of the bioreactor includes several ports including a mixing port, a reaction port, and a harvesting port. The agitator extends through the mixing port into the vessel while the harvesting outlet extends through the harvesting port and permits the withdrawal of reaction medium to another vessel, which may be part of a bioreactor system. The reaction assembly extends through the reaction port into the vessel and has multiple components including a gas conduit adapted to introduce gas into a reaction medium in the vessel, a sampling device adapted to remove a portion of the reaction medium from the vessel without contamination of the remaining reaction medium, and an introduction conduit permitting the introduction of at least the reaction medium into the vessel. [0012]The bioreactor may further include a water jacket adapted to regulate the temperature of the reaction medium. The gas conduit may be adapted to aerate the reaction medium. A sparger may be provided in the gas conduit of the reaction assembly to limit the bubble size of the gas introduced into the vessel. The agitator may extend through a cover sealing the mixing port. The agitator may be adapted to be coupled to an external drive device, for example, a motor. [0013]The sampling device may comprise a collection conduit extending into the vessel, a sampling valve positioned in the collection conduit and disposed outside the vessel, and an extractor associated with the collection conduit and disposed outside of the vessel. The extractor may be adapted to remove a sample portion of reaction medium through the collection conduit. A discharge outlet may be provided for releasing the sample portion of reaction medium from the collection conduit outside of the vessel without contamination of the remaining reaction medium. The extractor may further comprise a vacuum generating portion adapted to decrease pressurization in the collection conduit, and a filter element provided fluidly between the vacuum generating portion and the collection conduit. [0014]The bioreactor may be used as part of a bioreactor system for performing biological and/or biochemical reactions. In such a system, the system includes a seed bioreactor comprising a vessel, an agitator, a reaction assembly, and a harvesting outlet. The vessel of the bioreactor includes several ports including a mixing port, a reaction port, and a harvesting port. The agitator extends through the mixing port into the vessel while the harvesting outlet extends through the harvesting port and permits the withdrawal of reaction medium. The reaction assembly extends through the reaction port into the vessel and has multiple components including a gas conduit adapted to introduce gas into a reaction medium in the vessel, a sampling device adapted to remove a portion of the reaction medium from the vessel without contamination of the remaining reaction medium, and an introduction conduit permitting the introduction of at least the reaction medium into the vessel. The seed bioreactor may be used to "seed" a main (e.g., larger) bioreactor with reaction medium for continuing the biological and/or biochemical reaction process. Such a main bioreactor is adapted to be placed in fluid communication with the vessel via the harvesting outlet and typically includes an inlet port. The main bioreactor may be placed in fluid communication with the vessel via a sanitary connection between the harvesting outlet and the inlet port. [0015]Another aspect of the invention is related to a method of assembling a bioreactor adapted to perform biological and/or biochemical reactions. The method includes providing a vessel comprising a mixing port, a reaction port, and a harvesting port; inserting an agitator into the vessel through the mixing port, with the agitator adapted to stir a reaction medium in the vessel; sealing the mixing port with a cover, with the agitator extending through the cover; sealing the reaction port with a reaction assembly extending through the reaction port and into the vessel; and sealing the harvesting port with a harvesting outlet adapted to permit the sterile withdrawal and transfer of reaction medium to another vessel. The reaction assembly generally comprises a gas conduit adapted to introduce gas into the vessel, a sampling device adapted to remove a portion of the reaction medium from the vessel without contamination of the remaining reaction medium, and an introduction conduit permitting the introduction of at least the reaction medium into the vessel. [0016]A further aspect of the invention relates to a method of preparing biological and/or biochemical reactants, generally comprising the steps of providing a seed bioreactor comprising a vessel having a mixing port, a reaction port, and a harvesting port. The method further includes introducing reactants (i.e., reaction medium) into the vessel through an introduction conduit extending through the reaction port; introducing gas into the reaction medium through a gas conduit extending through the reaction port; agitating the reaction medium with a mixer extending through the mixing port; and transferring at least a portion of the processed reaction medium to a main bioreactor through the harvesting port. [0017]Further details and advantages of the invention will become clear upon reading the following detailed description in conjunction with the accompanying drawing figures, wherein like parts are identified with like reference numerals throughout. BRIEF DESCRIPTION OF THE DRAWINGS [0018]FIG. 1 is an exploded and partially perspective view of a bioreactor pursuant to an embodiment of the present invention. [0019]FIG. 2 is an assembled and partially perspective view of the bioreactor of FIG. 1. [0020]FIG. 3 is a schematic diagram showing the bioreactor of FIG. 2 as part of a system wherein the bioreactor is a seed bioreactor for larger bioreactor devices. DETAILED DESCRIPTION OF THE INVENTION Continue reading... Full patent description for Bioreactor and method Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Bioreactor and method patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. 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