Patent Publication Number: US-10308907-B2

Title: Systems for inactivating fluid cultures through heating

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of U.S. application Ser. No. 14/621,021, filed Feb. 12, 2015, which is a continuation of U.S. application Ser. No. 14/075,933, filed Nov. 8, 2013, U.S. Pat. No. 8,961,875 which is a divisional of U.S. application Ser. No. 12/986,734, filed Jan. 7, 2011, U.S. Pat. No. 8,608,369, which are incorporated herein by specific reference in its entirety. 
    
    
     BACKGROUND OF THE INVENTION 
     1. The Field of the Invention 
     The present invention relates to systems for heating and mixing fluids which can be used for inactivating cells or microorganisms. 
     2. The Relevant Technology 
     The biopharmaceutical industry uses a broad range of mixing systems for a variety of processes such as in the preparation of media and buffers and in the growing or processing of cells and microorganisms. Many conventional mixing systems, including bioreactors, comprise a rigid tank that can be sealed closed. A drive shaft with impeller is rotatably disposed within the tank. The impeller functions to suspend and mix the components. 
     In many cases, great care must be taken to sterilize and maintain the sterility of the mixing system so that the culture or other product does not become contaminated. Accordingly, between the production of different batches, the mixing tank, mixer, and all other reusable components that contact the processed material must be carefully cleaned to avoid any cross contamination. The cleaning of the structural components is labor intensive, time consuming, and costly. For example, the cleaning can require the use of chemical cleaners such as sodium hydroxide and may require steam sterilization as well. The use of chemical cleaners has the additional challenge of being relatively dangerous, and cleaning agents can be difficult and/or expensive to dispose of once used. 
     Once processing step commonly used with biological fluids containing a culture is to heat the fluid to a defined temperature to kill or inactivate the cells or microorganisms therein. This has historically been accomplished by heating the fluid within a stainless steel tank. Such processing, however, again requires the cleaning and sterilization of the tank between different batches. 
     Accordingly, what is needed in the art are system that permit controlled and uniform heating of a fluid that does not require washing or sterilization between batches and that minimizes any potential for breach in sterility. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Various embodiments of the present invention will now be discussed with reference to the appended drawings. It is appreciated that these drawings depict only typical embodiments of the invention and are therefore not to be considered limiting of its scope. 
         FIG. 1  is perspective view of a fluid heating system incorporating features of the present invention; 
         FIG. 2  is a cross sectional side view of the tank assembly of the fluid heating system shown in  FIG. 1 ; 
         FIG. 3  is a bottom perspective view of the tank assembly shown in  FIG. 2 ; 
         FIG. 4  is a perspective view of the tank assembly shown in  FIG. 1  with the lid in a closed position; 
         FIG. 5  is a cross sectional side view of the fluid heating system shown in  FIG. 1 ; 
         FIG. 6  is a front side plan view of the container assembly shown in  FIG. 1  in a collapsed position; 
         FIG. 7  is a back side plan view of a container assembly shown in  FIG. 6  in a collapsed position; 
         FIG. 8  is an exploded perspective view of a temperature port assembly of the container assembly shown in  FIG. 6  with related parts; 
         FIG. 9  is a cross sectional side view of the temperature port assembly shown in  FIG. 8 ; 
         FIG. 10  is an elevated side view of an impeller assembly and drive shaft used in the fluid heating system; 
         FIG. 11  is a partially disassembled perspective view of the impeller assembly, drive shaft and drive motor assembly of the fluid heating system; 
         FIG. 12  is an enlarged view of the rotational assembly and drive motor assembly in a disassembled view state; and 
         FIG. 13  is an elevated front view of the rotational assembly and drive motor assembly coupled together. 
     
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     The present invention relates to systems and methods for heating fluids but can also be used for mixing and/or cooling fluids. The systems can commonly be used for inactivating cells or microorganism in a biological fluid by heating the fluid. For example, the systems can be used for inactivating yeast cells by heating media containing the cells to a defined temperature and then holding the media at the temperature for a defined time. The systems can be used with other cells or microorganism and can be used for heating and/or mixing other biological or non-biological fluids for other purposes such as sterilization or fluid processing. 
     The inventive systems are designed so that a majority of the system components that contact the material being processed can be disposed of after each use. As a result, the inventive systems substantially eliminate the burden of cleaning and sterilization required by conventional stainless steel mixing systems. This feature also ensures that sterility can be consistently maintained during repeated processing of multiple batches. In view of the foregoing, and the fact that the inventive systems are easily scalable, relatively low cost, and easily operated, the inventive systems can be used in a variety of industrial and research facilities that previously outsourced such processing. 
     Depicted in  FIG. 1  is one embodiment of an inventive fluid heating system  10  incorporating features of the present invention. In general, fluid heating system  10  comprises a tank assembly  12 , a container assembly  16  that is disposed within and supported by tank assembly  12 , and a drive shaft  18  ( FIG. 2 ) that extends between tank assembly  12  and container assembly  16 . Container assembly  16  houses the fluid or solution that is heated and can also be mixed and/or cooled. The various components of fluid heating system  10  will now be discussed in greater detail. 
     Continuing with  FIG. 1 , tank assembly  12  comprises a tank body  102  having a lid  104  hingedly coupled thereto. Tank body  102  comprises a substantially cylindrical sidewall  106  having an interior surface  108  that extends between an upper end  110  and an opposing lower end  112 . As depicted in  FIG. 2 , tank body  102  also includes a floor  114  located at lower end  112  with a drain opening  116  extending therethrough. Interior surface  108  of sidewall  106  and floor  114  bound a chamber  118 . As discussed below, chamber  118  is configured to receive container assembly  16  so that container assembly  16  is supported therein. A substantially C-shaped lip  120  is formed at upper end  110  of sidewall  106  and partially bounds an access opening  122  to chamber  118 . A pair of spaced apart slots  124 A and B are recessed on lip  120  and, as will be discussed below in greater detail, provide channels through which fluid lines can pass out of chamber  118  when lid  104  is closed. 
     In general, tank body  102  has a front face  126  and an opposing back face  128 . As best shown in  FIG. 1 , an enlarged notch  130  is formed on front face  126  at upper end  110  and extends through sidewall  106  and lip  120 . Disposed within notch  130  so as to communicate with chamber  118  is a drive motor assembly  132 . As will be discussed below in greater detail, drive motor assembly  132  is used to rotate drive shaft  18  ( FIG. 2 ) which in turn mixes the fluid within container assembly  16 . Although not required, drive motor assembly  132  is typically fitted so that notch  130  is sealed closed. A generally U-shaped flange  134  having a top surface  136  extends between opposing sides of notch  130  along an inside face of drive motor assembly  132 . Top surface  136  at opposing ends of flange  134  is flush with lip  120  so that lip  120  and flange  134  combine to form sealing surface  137  that bounds access opening  122  of chamber  118 . 
     As shown in  FIG. 3 , formed on back face  128  of tank body  102  is a hinge  138  that connects lid  104  to tank body  102 . Hinge  138  enables lid  104  to be manually moved between an open position as shown in  FIG. 1  and a closed position as shown in  FIG. 4 . A handle  142 , shown in this embodiment as having a U-shaped configuration, is formed on lid  104  to assist in movement of lid  104  between the two positions. Continuing with  FIG. 3 , a piston  140  has a first end hingedly coupled with a lid portion  141  of hinge  138  and an opposing second end hingedly coupled with tank body  102 . Piston  140  assists in smooth and controlled movement of lid  104  so that lid  104  does not unintentionally slam shut. Lid  104  has a notch  144  formed on a front face thereof opposite hinge  138 . Notch  144  is sized to receive drive motor assembly  132  when lid  104  is in the closed position ( FIG. 4 ). Returning to  FIG. 1 , lid  104  has an inside face  148  having a gasket  150  extending along a perimeter edge thereof. When lid  104  is in the closed position, gasket  150  sites on top of sealing surface  138  so that drain opening  116  to chamber  118  is substantially sealed closed. It is noted that when lid  104  is closed, slots  124 A and B ( FIG. 2 ) will still be open to chamber  118  which can be a source of heat loss. Such heat loss, however, is negligible. If desired, inserts can be placed within slots  124 A and B to seal them off when not in use. In some embodiments, slots  124 A and B can be eliminated. 
     As shown in  FIG. 4 , tank assembly  12  also includes a locking assembly  152  that helps to ensure a tight and secure sealed engagement between lid  104  and tank body  102 . In the embodiment depicted, locking assembly  152  includes a catch  154  formed on and radially outwardly projecting out from lid  104 . Catch  154  has a slot  155  ( FIG. 1 ) formed on an end face thereof. In turn, a fastener  156  is mounted on tank body  102  below catch  154 . Fastener  156  includes a threaded bolt  158  having a first end hingedly mounted to tank body  102  and an opposing second end having a handle  160  threaded thereon. When lid  104  is in the closed position, fastener  156  is rotated so that bolt  158  is received within slot  155  of catch  154 . Handle  160  can then be selectively rotated to advance along bolt  158 . In so doing, handle  160  biases against catch  154  and clamps lid  104  to tank body  102 . If desired, two or more locking assemblies  152  can be used. In alternative embodiments, it is appreciated that the depicted locking assembly  152  can be replaced with any number of conventional locking systems such as latches, clamps, fasteners, screws, elastic cords, or any other structure that can temporarily secure lid  104  to tank body  102 . In yet other embodiments, locking assembly  152  can be eliminated. 
     Although tank body  102  is shown as having a substantially cylindrical configuration, in alternative embodiments tank body  102  can have any desired shape capable of at least partially bounding a chamber. For example, sidewall  106  need not be cylindrical but can have a variety of other transverse, cross sectional configurations such as polygonal, elliptical, or irregular. Furthermore, it is appreciated that tank body  102  can be scaled to any desired size. For example, it is envisioned that chamber  118  of tank body  102  can be sized to hold a maximum volume of fluid in a range between about 50 liters to about 2,500 liters with about 75 liters to about 1,000 liters being common and about 75 liters to about 300 liters being more common. Other sizes can also be used. Tank body  102  and lid  104  are typically made of metal, such as stainless steel, but can also be made of other materials capable of withstanding the applied loads and temperatures of the present invention. 
     In one embodiment of the present invention means are provided for controlling the temperature of the fluid that is contained within container assembly  16  when container assembly  16  is disposed within chamber  118  of tank assembly  12 . By way of example and not by limitation, tank body  102  and lid  104  can both be jacketed so as to bound one or more fluid channels through which heated or cooled fluid can pass. In turn, heat from the heated fluid flowing through tank assembly  12  radiates to the fluid within container assembly  16  for heating the fluid therein. Alternatively, chilled fluid flowing through tank assembly  12  draws heat from the fluid within container assembly  16  for cooling the fluid therein. For example, as shown in  FIG. 2 , sidewall  106  comprises an inside wall  162  and an outside wall  164  that bound a fluid channel  166  therebetween; floor  114  comprises an inside wall  168  and an outside wall  170  that bound a fluid channel  172  therebetween; and lid  104  comprises an inside wall  174  and an outside wall  176  that bound a fluid channel  178  therebetween. If desired an insulation layer  179  can be positioned between each outside wall  164 ,  170 , and  176  and the corresponding fluid channel. 
     Turning to  FIG. 3 , outside wall  176  of lid  104  has an inlet port  180  and an outlet port  182  formed thereon and communicating with fluid channel  178  ( FIG. 2 ). A hose coupling  181  is coupled with inlet port  180 . Hose coupling  181  is designed to couple with a fluid line that extends from a thermal control unit (TCU)  197  or some other source for generating or providing a heated or cooled fluid so that the fluid can be pumped into fluid channel  178  at a desired temperature and flow rate. The fluid can be water, propylene glycol, or other types of fluids commonly used in this type of heating or cooling. In one embodiment, the TCU  197  can comprise a boiler  198  fluid coupled with a pump  199  which delivers the fluid to house coupling  181 . A chiller and other components can also be used. 
     Outside wall  162  of sidewall  106  has an inlet port  184  and an outlet port  186  formed thereon and communicating with fluid channel  166  ( FIG. 2 ). A fluid line  188  extends from outlet port  182  on lid  104  to inlet port  184  of sidewall  106  so that after the heated fluid passes through fluid channel  178  in lid  104  it can then pass through fluid channel  166  in sidewall  162 . In turn, outside wall  170  of floor  114  has an inlet port  190  and an outlet port  192  formed thereon and communicating with fluid channel  172  ( FIG. 2 ). A fluid line  194  extends from outlet port  186  on sidewall  106  to inlet port  190  of floor  114  so that after the heated fluid passes through fluid channel  166  in sidewall  162  it can then pass through fluid channel  172  in floor  114 . 
     Finally, a hose coupling  196  is coupled with outlet port  192  of floor  114  so that a fluid line can be coupled therewith and extend back to TCU  197  where the fluid is then heated or cooled back to the desired temperature before repeating the cycle. The fluid flow system can thus be a close loop, recirculating system. It is appreciated that partitions or other structures can be formed within fluid channels  166 ,  172 , and  178  to optimize fluid flow throughout so that tank body  102  and lid  104  apply a substantially uniform and continuous heat or cooling around all sides of container assembly  16  when container assembly  16  is disposed within tank assembly  12 . 
     In alternative embodiments, it is appreciated that the heated or cooled fluid can enter through hose coupling  190  on floor  114  and then exit out through hose coupling  181  on lid  104 . In still other embodiments, separate recirculating systems can be coupled with each of lid  104 , sidewall  106  and/or floor  114 . In contrast to using a heated liquid fluid, heated gas or steam can be used. Alternatively, the means for controlling the temperature can comprise electrical heating elements placed on the exterior surfaces of inside walls  162 ,  168 , and  174 . Other conventional heating or cooling systems can also be used. The means for controlling the temperature can be used to heat the fluid within container assembly  16  to a temperature in a range between about 30° C. to about 130° C. with about 50° C. to about 70° C. being more common. Other temperatures can also be used. 
     As also shown in  FIG. 2 , tank assembly  12  also includes a support  200  secured to interior surface  108  of sidewall  106  at upper end  110 . Support  200  includes a flange  202  attached to and projecting from sidewall  106  and a substantially C-shaped retainer  204  disposed at the end thereof. Retainer  204  includes a stem  206  and a flange  208  radially outwardly projecting therefrom, both stem  206  and a flange  208  having a substantially C-shaped configuration. As will be discussed below in greater detail, support  200  is used for supporting a portion of container assembly  16  and for supporting a temperature probe  210  therein. 
     As shown in  FIG. 1 , tank assembly  12  is typically mounted on a platform  212 . If desired, one or more load cells can be incorporated into platform  212  so that the quantity of fluid delivered to container assembly  12  when disposed within tank assembly  12  can be accurately measured.  FIG. 1  also shows an electrical controller  214 . Controller  214  can be used for measuring and controlling operational parameters such as the heat and flow rate of fluid through the fluid channels, as discussed above, tracking the time and temperature that the fluid within container assembly  12  is heated, measuring the weight of fluid entering container assembly  12  and controlling mixing of the fluid within container assembly  12  as will be discussed below in greater detail. 
     Turning to  FIG. 5 , container assembly  16  comprises a container  18  having a side  20  that extends from an upper end  22  to an opposing lower end  24 . Upper end  22  terminates at a top  23  while lower end  24  terminates at a bottom  25 . Container  18  also has an interior surface  26  that bounds a compartment  28 . Compartment  28  is configured to hold a fluid. In the embodiment depicted, container  18  comprises a flexible bag that is comprised of a flexible, water impermeable material such as a low-density polyethylene or other polymeric sheets having a thickness in a range between about 0.1 mm to about 5 mm with about 0.2 mm to about 2 mm being more common. Other thicknesses can also be used. The material can be comprised of a single ply material or can comprise two or more layers which are either sealed together or separated to form a double wall container. Where the layers are sealed together, the material can comprise a laminated or extruded material. The laminated material comprises two or more separately formed layers that are subsequently secured together by an adhesive. 
     The extruded material comprises a single integral sheet that comprises two or more layers of different materials that can be separated by a contact layer. All of the layers are simultaneously co-extruded. One example of an extruded material that can be used in the present invention is the Thermo Scientific CX3-9 film available from Life Technologies Corporation. The Thermo Scientific CX3-9 film is a three-layer, 9 mil cast film produced in a cGMP facility. The outer layer is a polyester elastomer coextruded with an ultra-low density polyethylene product contact layer. Another example of an extruded material that can be used in the present invention is the Thermo Scientific CX5-14 cast film also available from Life Technologies Corporation. The Thermo Scientific CX5-14 cast film comprises a polyester elastomer outer layer, an ultra-low density polyethylene contact layer, and an EVOH barrier layer disposed therebetween. In still another example, a multi-web film produced from three independent webs of blown film can be used. The two inner webs are each a 4 mil monolayer polyethylene film (which is referred to by Life Technologies Corporation as the Thermo Scientific BM1 film) while the outer barrier web is a 5.5 mil thick 6-layer coextrusion film (which is referred to by Life Technologies Corporation as the Thermo Scientific BX6 film). 
     The material is approved for direct contact with living cells and is capable of maintaining a solution sterile. In such an embodiment, the material can also be sterilizable such as by ionizing radiation. Examples of materials that can be used in different situations are disclosed in U.S. Pat. No. 6,083,587 which issued on Jul. 4, 2000 and United States Patent Publication No. US 2003/0077466 A1, published Apr. 24, 2003 which are hereby incorporated by specific reference. 
     In one embodiment, container  18  comprise a two-dimensional pillow style bag wherein two sheets of material are placed in overlapping relation and the two sheets are bonded together at their peripheries to form the internal compartment. Alternatively, a single sheet of material can be folded over and seamed around the periphery to form the internal compartment. In another embodiment, container  18  can be formed from a continuous tubular extrusion of polymeric material that is cut to length and is seamed closed at the ends. 
     In still other embodiments, container  18  can comprise a three-dimensional bag that not only has an annular side wall but also a two dimensional top end wall and a two dimensional bottom end wall. Three dimensional containers comprise a plurality of discrete panels, typically three or more, and more commonly four or six. Each panel is substantially identical and comprises a portion of the side wall, top end wall, and bottom end wall of the container. Corresponding perimeter edges of each panel are seamed. The seams are typically formed using methods known in the art such as heat energies, RF energies, sonics, or other sealing energies. 
     In alternative embodiments, the panels can be formed in a variety of different patterns. Further disclosure with regard to one method of manufacturing three-dimensional bags is disclosed in United States Patent Publication No. US 2002/0131654 A1 that was published Sep. 19, 2002 of which the drawings and Detailed Description are hereby incorporated by reference. 
     Although in the above discussed embodiment container  18  has a flexible, bag-like configuration, in alternative embodiments it is appreciated that container  18  can comprise any form of collapsible container or semi-rigid container. Container  18  can also be transparent or opaque and can have ultraviolet light inhibitors incorporated therein. 
     It is appreciated that container  18  can be manufactured to have virtually any desired size, shape, and configuration. For example, container  18  can be formed having a compartment sized to 10 liters, 30 liters, 100 liters, 250 liters, 500 liters, 750 liters, 1,000 liters, 1,500 liters, 3,000 liters, 5,000 liters, 10,000 liters or other desired volumes and thus can be in a range between any of the above volumes. Although container  18  can be any shape, in one embodiment container  18  is specifically configured to be complementary or substantially complementary to chamber  118  of tank body  102 , as discussed above. 
     In any embodiment, however, it is typically desirable that when container  18  is received within the chamber  118 , container  18  is at least generally uniformly supported by tank body  102 . Having at least general uniform support of container  18  by tank body  102  helps to preclude failure of container  18  by hydraulic forces applied to container  18  when filled with fluid. 
     Depicted in  FIG. 6  is a front side view of container assembly  16  with container  18  in a folded or collapsed position. As shown therein, container assembly  16  includes ports  230 A and B secured to upper end  22  of container  18 . Ports  230 A and B can be secured by welding or other conventional techniques and include a passageway extending therethrough that communicates with compartment  28  ( FIG. 5 ). Coupled with and extending from ports  230 A and B are fluid lines  232 A and B, respectfully. Fluid lines  232 A and B are typically comprised of a flexible hose or tubing. Mounted on the end of fluid line  232 A and B are connectors  234 A and B, respectfully. Connectors  234 A and B are designed for forming a fluid coupling with an additional fluid line, container, or other structure. In one embodiment, connectors  234 A and B can comprise aseptic connectors such as the KLEENPAK sterile connector available from the Pall Corporation. Other sterile or non-sterile connectors can also be used. An envelope  235  is removable positioned over each connector  234 A and B to help maintain sterility prior to use. A tube clamp  238  can also be mounted on each fluid line  232 A and B for closing the fluid lines or controlling the flow of gas or liquid therethrough. Fluid lines  232 A and B are commonly used for delivering liquids, gases or other components into or out of container  18 . 
     Also mounted at upper end  22  of container  18  is a port  240  having a gas line  242 , typically in the form of a flexible hose or tube, extending therefrom and having a gas filter  244  mounted on the end thereof. Gas filter  244  typically has a barbed port  246  formed on the end thereof for removably receiving a gas line that is coupled with a compressor or other gas source. As will be discussed below in more detail, for proper positioning, expansion and filling of container  18 , it is helpful to initially partially fill container  18  with a gas, such as air. The gas can be delivered through port  246  on gas filter  244 . Gas filter  244  filters the gas so that no contaminates enter container  18 . Once container assembly  16  is properly positioned within tank assembly  12 , fluid and other components can be delivered into container  18  through one of fluid lines  232 A or B while the displaced gas exits out through the other fluid line  232 A or B. A tube clamp  238  can also be positioned on gas line  242  to selectively close off the passage therethrough. 
     Finally, also mounted at upper end  22  of container  18  is a temperature port assembly  250 . Turning to  FIG. 8 , temperature port assembly  250  comprises a port  252  that is secured to container  18  and a probe adapter  254  that is coupled with port  252 . Port  252  has a conventional design that includes a barbed stem  256  having a passage  258  extending therethrough and a flange  260  radially outwardly projecting therefrom. Flange  260  is welded or otherwise secured to container  18  so that passage  258  communicates with compartment  28  ( FIG. 5 ). Probe adapter  254  comprises a flexible sleeve  264  having a first end  266  and an opposing second end  268 . Encircling and radially outwardly projecting from first end  266  is a mounting flange  270 . Likewise, encircling and radially outwardly projecting from second end  268  is a support flange  272 . A tubular stem  274  projects in axial alignment with sleeve  264  from a side of mounting flange  270  opposite of sleeve  264 . 
     Probe adapter  254  also includes an elongated receiver  276  having a first end  278  and an opposing second end  280 . As shown in  FIG. 9 , receiver  276  includes an elongated body  281  that typically has a substantially cylindrical configuration and extends between first end  278  and second end  280 . Body  281  has an interior surface  282  that bound a cavity  284 . Body  281  is closed except for an opening  286  formed at first end  278 . A tubular catch  288  is mounted on and projects from first end  278  of body  281  in alignment with opening  286 . A flange  289  encircles and radially outwardly projects from body  281  at first end  286 . 
     During assembly, second end  280  of body  281  is passed down through stem  274 , mounting flange  270 , sleeve  264 , and supporting flange  272  so that second end  280  projects down below support flange  272 . Body is advanced until flange  289  rests against stem  274 . In this configuration, a friction tight fit is formed between body  281  and stem  274 . However, during radiation sterilization of container assembly  16 , body  281  and stem  274  can weld together. Otherwise, if desired, an adhesive or other conventional welding techniques can be used to secure the structures together. In yet other embodiments, probe adapter  254  can be formed as a single unitary member or as other combinations of members secured together. 
     As also shown in  FIG. 9 , a cavity  290  is also formed between an interior surface  291  of sleeve  264  and the exterior surface of receiver  276 . During assembly, port  252  is slid into cavity  290 , the parts being sized so that a friction fit is formed therebetween. A tie  292  can then be cinched around sleeve  264  so as to ensure a liquid type seal between sleeve  264  and port  252 . 
     In the assembled configuration, sleeve  264  is inserted within retainer  204  ( FIG. 2 ) of tank body  102  so that mounting flange  270  rests on flange  208  of retainer  204 . An annular gasket  294  having an opening  295  ( FIG. 8 ) extending therethrough, is then positioned on top of mounting flange  270 . Finally, a clamp  296  ( FIG. 8 ), such as a tri-clamp, is positioned around flange  208 , mounted flange  270  and gasket  294  so that when clamp  296  is closed and tightened, these structures are securely held together. Port  252  and the portion of container  18  secured thereto are thus secured to and supported by retainer  204 . An elongated temperature probe  210 , commonly referred to as an RTD, can be advanced down into cavity  284  of receiver  276 . A collar  298  mounted on probe  210  can be threaded onto catch  288  so as to secure temperature probe  210  to receiver  276 . 
     By inserting temperature probe  210  within receiver  276 , temperature probe  210  can measure the temperature of the fluid within container  18  through the wall of receiver  276 . Receiver  276  protects temperature probe  210  from directly contacting the fluid within container  18 . As such, there is no risk of temperature probe  210  contaminating the fluid and temperature probe  210  can be reused without sterilization or other cleaning. Furthermore, temperature probe  210  is rigidly held in position at a distance spaced apart from sidewall  162 . As such, temperatures probe  210  give a more accurate reading of the temperature of the fluid than if it was positioned adjacent to sidewall  162 . Temperatures probe  210  is also held at a constant location independent of whether fluid is being added or removed from container  18 . 
     Returning to  FIG. 6 , container assembly  16  also comprises a port  308  mounted at lower  24  of container  18 , a drain line  310  extending from port  308 , and a tube connector  312 , such as a sterile connector, mounted at the end of drain line  310 . A hose clamp  238  is also mounted on drain line  310  for closing the passage therethrough. Finally, a support plate  314  is shown encircling drain line  310  adjacent to port  308 . As shown in  FIG. 3 , drain opening  116  is typically formed oversized so that it is easy to reach up through drain opening  116  and grab drain line  310  or to otherwise pass drain line  310  down through drain opening  116 . Support plate  314  is simply a plate that is configured to be received within drain opening  116  after drain line  310  passes therethrough so that container  18  can be supported thereon. Support plate  314  can have a slot  316  extending therethrough and radially extending in from the perimeter edge so that drain line  310  can be removably slid into slot  316 . Alternatively, support plate  314  can simply have a central hole through which drain line  310  is passed during the assembly of container assembly  16 . 
     If desired, other ports can be mounted on container  18  for use in coupling other probes to container  18 . For example, other ports can be used for coupling probes such as pH probes, dissolved oxygen probes, and the like. Examples of ports and how various probes and lines can be coupled thereto is disclosed in United States Patent Publication No. 2006/0270036, published Nov. 30, 2006 and United States Patent Publication No. 2006/0240546, published Oct. 26, 2006, which are incorporated herein by specific reference. Ports can also be used for coupling container  18  to secondary containers, to condenser systems, and to other desired fittings. 
     Depicted in  FIG. 7  is a back side view of container assembly  16  with container  18  in a folded or collapsed position. As shown therein, container assembly  16  further comprises an impeller assembly  40 . As depicted in  FIG. 10 , impeller assembly  40  comprises an elongated tubular connector  44  having a rotational assembly  48  mounted at one end and an impeller  64  mounted on the opposing end. More specifically, tubular connector  44  has a first end  46  and an opposing second end  48  with a passage  50  that extends therebetween. In one embodiment, tubular connector  44  comprises a flexible tube such as a polymeric tube. In other embodiments, tubular connector  44  can comprise a rigid tube or other tubular structures. 
     Rotational assembly  48  is mounted to first end  46  of tubular connector  44 . Rotational assembly  48  comprises an outer casing  50  having an outwardly projecting flange  52  and a tubular hub  54  rotatably disposed within outer casing  50 . A bearing assembly can be disposed between outer casing  50  and tubular hub  54  to permit free and easy rotation of hub  54  relative to casing  50 . Likewise, one or more seals can be formed between outer casing  50  and tubular hub  54  so that during use an aseptic seal can be maintained between outer casing  50  and tubular hub  54  as tubular hub  54  rotates relative to outer casing  50 . 
     Hub  54  has an interior surface  56  that bounds an opening  58  extending therethrough. As will be discussed below in greater detail, an engaging portion of interior surface  56  has a polygonal or other non-circular transverse cross section so that a driver portion of drive shaft  362  passing through opening  58  can engage the engaging portion and facilitate rotation of hub  54  by rotation of drive shaft  362 . Hub  54  can also comprise a tubular stem  60  projecting away from outer casing  50 . Hub  54  can couple with first end  44  of tubular connector  42  by stem  60  being received within first end  44 . A pull tie, clamp, crimp or other fastener can then be used to further secure stem  60  to tubular connect  42  so that a liquid tight seal is formed therebetween. Other conventional connecting techniques can also be used. 
     Impeller  64  comprises a central hub  66  having a plurality of fins  68  radially outwardly projecting therefrom. It is appreciated that a variety of different numbers and configurations of fins  68  can be mounted on hub  66 . Hub  66  has a first end  70  with a blind socket  72  formed thereat. Socket  72  typically has a non-circular transverse cross section, such as polygonal, so that it can engage a driver portion of drive shaft  362 . Accordingly, as will be discussed below in greater detail, when a driver portion is received within socket  72 , the driver portion engages with impeller  64  such that rotation of drive shaft  362  facilities rotation of impeller  64 . 
     In one embodiment, hub  66  and fins  68  of impeller  64  are molded from a polymeric material. In alternative embodiments, hub and fins  68  can be made of metal, composite, or a variety of other materials. If desired, an annular insert can be positioned within socket  72  to help reinforce hub  66 . For example, the insert can be comprised of metal or other material having a strength property greater than the material from which hub  66  is comprised. 
     Impeller  64  can be attached to connector  42  by inserting first end  70  of hub  66  within connector  42  at second end  46 . A pull tie, clamp, crimp, or other type of fastener can then be cinched around second end  46  of connector  42  so as to form a liquid tight sealed engagement between impeller  64  and connector  42 . 
     Returning to  FIG. 7 , rotational assembly  48  is secured to container  18  so that tubular connector  42  and impeller  64  extend into or are disposed within compartment  28  of container  18  ( FIG. 5 ). Specifically, in the depicted embodiment container  18  has an opening  74  at upper end  22 . Flange  52  of outer casing  50  is sealed around the perimeter edge bounding opening  74  so that hub  54  is aligned with opening  74 . Tubular connector  42  having impeller  64  mounted on the end thereof projects from hub  54  into compartment  28  of container  18 . In this configuration, outer casing  50  is fixed to container  18  but hub  54 , and thus also tubular connector  42  and impeller  64 , can freely rotate relative to outer casing  50  and container  18 . As a result of rotational assembly  48  sealing opening  74 , compartment  28  is sealed closed so that it can be used in processing sterile fluids. 
     As depicted in  FIG. 10 , impeller assembly  40  is used in conjunction with drive shaft  362 . In general drive shaft  362  comprises a head section  364  and a shaft section  366  that can be coupled together by threaded connection or other techniques. Alternatively, draft shaft  362  can be formed as a single piece member or from a plurality of attachable sections. Drive shaft  362  has a first end  368  and an opposing second end  370 . Formed at first end  368  is a frustoconical engaging portion  372  that terminates at a circular plate  374 . Notches  376  are formed on the perimeter edge of circular plate  374  and are used for engaging drive shaft  362  with drive motor assembly  132  as will be discussed below. 
     Formed at second end  370  of drive shaft  362  is a driver portion  378 . Driver portion  378  has a non-circular transverse cross section so that it can facilitate locking engagement within hub  66  of impeller  64 . In the embodiment depicted, driver portion  378  has a polygonal transverse cross section. However, other non-circular shapes can also be used. A driver portion  380  is also formed along drive shaft  362  toward first end  368 . Driver portion  380  also has a non-circular transverse cross section and is positioned so that it can facilitate locking engagement within the interior surface of hub  54  of rotational assembly  48 . 
     During use, as will be discussed below in further detail, drive shaft  362  is advanced down through hub  54  of rotational assembly  48 , through tubular connecter  42  and into hub  66  of impeller  64 . As a result of the interlocking engagement of driver portions  378  and  380  with hubs  66  and  54 , respectively, rotation of drive shaft  362  by a drive motor assembly facilitates rotation of hub  54 , tubular connecter  42  and impeller  64  relative to outer casing  50  of rotational assembly  48 . As a result of the rotation of impeller  64 , fluid within container  18  is mixed. 
     It is appreciated that impeller assembly  40 , drive shaft  362  and the discrete components thereof can have a variety of different configuration and can be made of a variety of different materials. Alternative embodiments of and further disclosure with respect to impeller assembly  40 , drive shaft  362 , and the components thereof are disclosed in United States Patent Publication No. 2011/0188928, published Aug. 4, 2011 which is incorporated herein in its entirety by specific reference. 
     As previously discussed with regard to  FIG. 1 , tank assembly  12  comprises drive motor assembly  132  mounted to sidewall  106 . Drive motor assembly  132  is used in conjunction with drive shaft  362  ( FIG. 10 ) and can be used for mixing and/or suspending a culture, solution, or other fluids within container  18  ( FIG. 2 ). Turning to  FIG. 11 , drive motor assembly  132  comprises a housing  304  having a top surface  306  and an opposing bottom surface  308 . An opening  310  extends through housing  304  from top surface  306  to bottom surface  308 . A tubular motor mount  312  is rotatably secured within opening  310  of housing  304 . Upstanding from motor mount  312  is a locking pin  316 . A drive motor  314  is mounted to housing  304  and engages with motor mount  312  so as to facilitate select rotation of motor mount  312  relative to housing  304 . Drive shaft  362  is configured to pass through motor mount  312  so that engaging portion  372  of drive shaft  362  is retained within motor mount  312  and locking pin  316  of motor mount  312  is received within notch  376  of drive shaft  362 . As a result, rotation of motor mount  312  by drive motor  314  facilitates rotation of drive shaft  362 . Further discussion of drive motor assembly  132  and how it engages with drive shaft  362  and alternative designs of drive motor assembly  132  are provided in United States Patent Publication No. 2011/0188928 which was previously incorporated herein by specific reference. 
     To facilitate operation, rotational assembly  48  is coupled with drive motor assembly  132 . Specifically, as depicted in  FIG. 12 , housing  304  of drive motor assembly  132  has an open access  384  that is recessed on a front face  386  so as to communicate with opening  310  extending through housing  304 . Access  384  is in part bounded by a substantially C-shaped first side wall  388  that extends up from bottom surface  308 , a concentrically disposed substantially C-shaped second side wall  390  disposed above first side wall  388  and having a diameter larger than first side wall  388 , and a substantially C-shaped shoulder  392  extending between side walls  388  and  390 . As shown in  FIG. 5 , a door  394  is hingedly mounted to housing  304  and selectively closes the opening to access  384  from front face  386 . Returning to  FIG. 12 , door  394  is secured in a closed position by a latch  396 . Positioned on first side wall  388  is a section  398  of a resilient and/or elastomeric material such as silicone. Other sections  398  of similar materials can also be positioned on first side wall  388  or the interior surface of door  394 . 
     As depicted in  FIG. 13 , to facilitate attachment of rotational assembly  48  to housing  304 , with door  394  rotated to an open position, rotational assembly  48  is horizontally slid into access  384  from front face  386  of housing  304  so that a support flange  400  radially outwardly extending from an upper end of rotational assembly  48  rests on shoulder  392  of access  384 . Rotational assembly  48  is advanced into access  384  so that the passage extending through hub  54  of rotational assembly  48  aligns with the passage extending through motor mount  312  ( FIG. 11 ). In this position, door  394  ( FIG. 5 ) is moved to the closed position and secured in the closed position by latch  396 . As door  394  is closed, casing  50  of rotational assembly  48  is biased against the one or more sections  398  ( FIG. 12 ) of resilient material so as to clamp rotational assembly  48  within access  384  and thereby prevent unwanted rotational movement of casing  50  relative to housing  304  of drive motor assembly  132 . 
     Once rotational assembly  48  is secured to drive motor assembly  132 , drive shaft  362  ( FIG. 10 ) can be advanced down through drive motor assembly  132  and into impeller assembly  40  so as to engage impeller  64 . Once drive shaft  362  is properly positioned, drive motor assembly  132  can activated causing drive shaft  362  to rotate impeller  64  and thereby mix or suspend the fluid within container  18 . 
     On embodiment of the present invention includes means for mixing the fluid within container  18 . One example of such means comprises impeller assembly  40 , draft shaft  362  and drive motor assembly  132 . In alternative embodiments of the means for mixing, impeller assembly  40  can be replaced with a drive shaft that extends through a dynamic seal on container  18  and has an impeller mounted on the end thereof within container  18 . In yet other embodiments, the means for mixing can comprise a stir bar, impeller or other form of mixer disposed within container  18  and a magnetic mixer disposed outside of container  18  that can rotate the mixer within container  18  through the use of a magnetic force. Other conventional mixers can also be used. 
     One typical example of how the inventive fluid heating system  10  can be used will now be provided. Initially, container assembly  16  is fabricated at a plant so that it is collapsed and sterilized as a complete assembly. Either just prior to or after placement of container assembly  16  within compartment  28  of tank assembly  12 , container assembly  16  is partially filled with a gas through gas filter  244  ( FIG. 6 ). By so doing, container assembly  16  expands enabling it to be easily positioned within and coupled to tank assembly  12 . Specifically, as shown in  FIG. 5 , drain line  310  is passed out through drain opening  116  in floor  114  and support plate  314  is fitted within drain opening  116 ; temperature port assembly  215  is coupled with retainer  204  of tank assembly  12  and rotational assembly  48  of container assembly  16  is coupled with drive motor assembly  132  of tank assembly  12  each has previously discussed. At different stages, more gas can be injected into container assembly  16  to ensure proper placement and coupling of container assembly  16  and to avoid any potential risk of kinking container  18  as it is filled with liquid. 
     Once container assembly  16  is properly positioned, fluid line  232 A is coupled with a fluid source while fluid line  232 B is coupled with a gas outlet line. These couplings are made aseptically so as to ensure no breach in sterility. The desired fluid is then dispensed into container  18  through fluid line  232 A while the displace gas is passed out through fluid line  232 B. As desired, the fluid and components thereof can be delivered in different stages. For example, container assembly  16  can initially be substantially filled with media followed by delivering a culture of cells or microorganisms. During this fluid filling and gas evacuation process, fluid lines  232 A and  232 B can pass out of tank assembly  12  through slots  124 A and B on lip  120 . This ensures that if lid  104  is closed, that the fluid lines are not damaged. At some stage, temperature probe  210  is secured within probe adaptor  254  as discussed above. The electrical wires extending from temperature probe  210  can likewise pass out through a slot  320  formed on lip  120  of tank assembly  12  as shown in  FIG. 1 , so as to avoid any damage thereto when lid  104  is closed. 
     With rotational assembly  48  secured to drive motor assembly  132 , drive shaft  362  is passed down through drive motor assembly  132  and into impeller assembly  40  where it couples with impeller  64 . Once all of the attachments and couplings are complete and container  18  is filled with the desired fluid, clamps  238  are closed on fluid lines  232 A and  232 B ( FIG. 6 ) so as to close off any further communications through the lines. Fluid lines  232 A and  232 B can then be disconnected from the fluid source and the gas outlet line after which the entire fluid lines  232 A and  232 B can be coiled and placed on top of container  18  within tank assembly  12 . Lid  104  is then closed and locked in place using fastener  156 . 
     Either before or after closing lid  104 , drive motor assembly  132  is activated to begin mixing fluid within container assembly  16 . This mixing of the fluid is not always required by helps to ensure that all of the fluid is uniformly heated within container  18 . Furthermore, the mixing helps to ensure that the fluid is homogeneous when it is dispensed for subsequent use. Heated fluid is pumped through the jacket of tank assembly  12  so that fluid within container  18  is heated. The heating can be started at any stage, i.e., before or after disconnecting fluid line  232 A from the fluid source. By having lid  104  closed and all sides of tank assembly  12  heated, along with the fluid in container  18  being mixed, the fluid can be uniformly and accurately heated with precision. The fluid is typically heated to a desired temperature after which that temperature is maintained for desired period of time to achieve desired results. 
     For example, to inactivate yeast, the fluid within container  18  is heated to a temperature of approximately 60° and maintained at that temperature for approximately 75 minutes. The temperature and the time for maintaining the temperature can vary depending on the desired processing. Furthermore, the temperature may be raised or lowered at different stages. Likewise, in contrast to using tank assembly  12  for heating, it is also appreciated that chilled fluid can be passed through the jacket of tank assembly  12  for chilling the fluid within container assembly  16 . 
     To ensure that all of the fluid in container assembly  16  is properly heated, an electrical heating element  322 , as shown in  FIG. 5 , can be wrapped around the portion of drain line  310  extending between contain  18  and clamp  238 . Electrical heating element  322  can heat the fluid within drain line  310  to the same temperature as the fluid within container  18 . This ensure proper heating of the fluid within drain line  310 . Clamp  238  is not opened until after all of the fluid has been properly heated. 
     Once the fluid within container assembly  16  has been properly processed, the heating can be discontinued. Drain line  310  can then be coupled in a sterile manner with a container or further line for draining fluid from container  18 . If desired, mixing of the fluid within container  18  may continue to ensure that the fluid is homogeneous as it is dispensed. 
     When the processing is complete, drive shaft  362  is removed and rotational assembly  48  is separated from drive motor assembly  132 . Container assembly  16  can then be separated from tank assembly  12  and disposed of. A second container assembly  16  can then be couple with tank assembly  12  in the same manner as discussed above and the process repeated. 
     The present invention may be embodied in other specific forms without departing from its spirit or essential characteristics. The described embodiments are to be considered in all respects only as illustrative and not restrictive. The scope of the invention is, therefore, indicated by the appended claims rather than by the foregoing description. All changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope.