Abstract:
An easily cleaned and/or sterilized fluid pumping assembly including a first pump housing including a first inner chamber. The first pump housing includes a fluid access port adapted to provide fluid communication between an outside of the first pump housing and the first inner chamber. Also, included is a second pump housing having a first coupling flange securely mated to the first pump housing. The second pump housing includes a second coupling flange adapted to be removeably and securely mated to a third coupling flange on a piston housing. Additionally, a flexible diaphragm is provided disposed between the first and second pump housings. The diaphragm is in fluid communication with the first inner chamber. Also, the diaphragm is displaceable by a driven piston for expelling fluid from the first inner chamber. More than one such assembly is used in combination to provide a constant flow fluid delivery system.

Description:
[0001]    The present application claims priority to provisional patent Application Ser. No. 60/679,524, filed May 10, 2005. This earlier filed provisional application is incorporated herein by reference. 
     
    
     BACKGROUND OF THE INVENTION 
       [0002]    Many fluid handling applications in biotechnology require a pump to move the fluid. Generally, when handling biological fluids it is important to ensure that an uncontaminated environment has been maintained throughout the process. Thus, the pumps are designed to be easily cleaned and sanitized before and after each use, thus controlling or reducing microbial contamination. In particular, contemporary biotechnological filtration and/or chromatography require equipment to be sanitized prior to use in order to ensure a fluid handling environment with minimal microbial contamination. 
         [0003]    In some chromatography processes, one or several liquid solutions are pumped into a chromatography column filled with a resin which varies depending on the particular process. The liquid flow rate must be constant and accurately controlled, while maintaining a relatively high degree of pressure (several bars/atmospheres or more) in order to drive the liquid through the column. Similarly, in a filtration process a relatively high degree of pressure is used to drive a liquid through a filter (normal or direct flow) or across a filter (cross or tangential flow). The latter is commonly used when liquid is re-circulated across a filter membrane. In such cross flow applications a precise flow rate and high pressure is required to ensure that more than a minor percentage of fluid flows through the filter relative to the recirculation rate. The high pressure is required to help drive the liquid through certain filters (such as membrane or cross-flow ultra-filters) that resist or limit the passage of fluid. Thus, as in chromatography, the fluid flow rate in filtration must often be accurately controlled, while maintaining several bars/atmospheres or more of pressure. 
         [0004]    Peristaltic pumps are commonly used in biotechnological applications because they do not contact the liquid stream but only the outside of the process tubing, only the inner diameter of the process tubing comes in contact with the liquid stream. They operate by means of a constriction that moves along the tubing, thus its parts avoid contact, and thus contamination, of the handled liquid. However, such tubing pumps are limited to lower pressure applications. A high pressure environment, such as several bars/atmospheres requires heavier gauge or reinforced tubing, which is no longer flexible enough to be pinched or squeezed. Thus, the peristaltic pumps are not suited for high pressure environments. 
         [0005]    Sanitary rotary lobe pumps are commonly used in biotechnology processes. These pumps can operate at relatively high pressures but they contain numerous components, such as the pump rotors, that contact the liquid stream. The contaminated components must be cleaned and sanitized after each use and possibly disassembled. Such a process can have added costs and delays that are not desirable. Also, this process requires high quality components that can withstand the added wear, which can also increase costs. Additionally, the type of precision components generally used as well as the relatively large number that get contaminated with each use, makes those parts too valuable to throw away after a single or small number of uses. 
         [0006]    It is therefore desirable to provide a fluid pumping system that is suitable for relatively high pressure environments, while preferably maintaining a constant and accurate fluid flow rate. Also, the system must be easily sterilized or uncontaminated between uses. 
       SUMMARY OF THE INVENTION 
       [0007]    The present invention relates to an apparatus for pumping fluids that is easily cleaned and/or sterilized after each use. Preferably, any parts contaminated by fluid contact can be easily removed and replaced. Also, those contaminated parts should be easily sterilized or designed to be disposable and thus replaced with inexpensive replacements. Using the preferred diaphragm pump of the present invention, few elements ever come in contact with the handled fluid, while providing a low shear, efficient, low cost method and system of pumping biological fluids. Additionally, the invention provides an apparatus and system that provides a constant and accurate fluid flow rate, while able to operate in relatively high fluid pressure environments. 
         [0008]    In one aspect of the present invention, a fluid pumping apparatus is provided that includes a first pump housing including a first inner chamber. The first pump housing includes a fluid access port adapted to provide fluid communication between an outside of the first pump housing and the first inner chamber. Also, included is a second pump housing having a first coupling flange securedly mated to the first pump housing. The second pump housing includes a second coupling flange adapted to be removeably and securedly mated to a third coupling flange on a piston housing. Additionally, a flexible diaphragm is provided disposed between the first and second pump housings. The diaphragm is in fluid communication with the first inner chamber. Also, the diaphragm is adapted to be displaced by a driven piston for expelling fluid from the first inner chamber. 
         [0009]    In another aspect of the present invention a fluid pumping apparatus is provided that includes a first pump housing with a first inner chamber. The first pump housing includes a fluid access port adapted to provide fluid communication between an outside of the first pump housing and the first inner chamber. A second pump housing is provided that includes a second inner chamber. The second pump housing is secured to the first pump housing. Further provided is a flexible diaphragm disposed between the first and second pump housings. The diaphragm is in fluid communication with the first inner chamber. Yet further, a third pump housing is provided that is removeably secured to the second pump housing. The third pump housing includes a piston access port. Also, the first, second and third pump housings are adapted to form a continuous unitary outer pump shell. Additionally a driven piston is adapted to move the flexible diaphragm toward the fluid access port. 
         [0010]    In yet another aspect of the current invention a chromatography pump assembly is provided that is adapted to deliver fluid at a constant flow rate. The pump assembly comprising a first conduit for receiving fluid, a second conduit for expelling fluid, a first and second diaphragm pump in fluid communication with the first and second conduits and a valve system. Each pump includes an inner fluid chamber, an inner flexible diaphragm, and a rigid drive mechanism adapted to push the diaphragm thereby expelling fluid from the inner fluid chamber. The valve system is adapted to block fluid flow from the first conduit to one of the first and second pumps, while simultaneously blocking fluid flow to the second conduit from the other of the first and second pumps. 
         [0011]    In yet another aspect of the current invention a method for pumping a fluid is described comprising providing conduit adapted to communicate fluid from at least one source to at least one destination. Then, coupling a first disposable and/or sterilized diaphragm pump to an intermediate position of the conduit. The first diaphragm pump is adapted to expel fluid by activation of a driven piston. Additionally, securing a piston housing for the driven piston to the first pump. Thus, the piston housing and the first pump forming a unitary continuous outer pump shell. Then, initiating the driven piston thereby pumping fluid out of the diaphragm pump. Thereafter, removing and discarding the first diaphragm pump after a single use, and replacing the first diaphragm pump with a second diaphragm pump. The second diaphragm pump being disposable and/or sterilized prior to use as part of the assembly. 
         [0012]    These and other objectives, features, and advantages of this invention will become apparent from the following detailed description of illustrative embodiments thereof, which is to be read in connection with the accompanying drawings. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0013]      FIG. 1  is a cross-sectional view of an embodiment of a fluid pumping apparatus in accordance with the subject invention. 
           [0014]      FIG. 2  is an exploded cross-sectional view of an upper pump housing, fluid conduit and valve assembly, in accordance with the subject invention. 
           [0015]      FIG. 3  is a cross-sectional view of an alternate embodiment of the upper pump housing shown in  FIG. 2 , in accordance with the subject invention. 
           [0016]      FIG. 4  is an exploded cross-sectional view of the upper pump housing shown in  FIG. 2  with an alternate embodiment fluid conduit, in accordance with the subject invention 
           [0017]      FIG. 5  is a cross-sectional view of a further embodiment of a fluid pumping apparatus in accordance with the subject invention. 
           [0018]      FIG. 6  is a partial schematic and cross-sectional view of a fluid pumping system using two of the fluid pumping apparatus shown in  FIG. 5 . 
           [0019]      FIGS. 7   a - c  are top, front and right-side views, respectively, of a fluid handling assembly, using two fluid pumping apparatus in accordance with the subject invention. 
           [0020]      FIG. 8  is a cross-sectional view of an alternate embodiment of the upper pump housing shown in  FIG. 2 , in accordance with the subject invention. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0021]    With reference to the drawings,  FIG. 1  shows a fluid pump head  100  adapted to be mounted and sealed with a piston assembly, in accordance with an embodiment of the invention. The diaphragm pump  100  is preferably formed by an upper pump housing  120  and a lower pump housing  160 , that when sealed together form an outer pump casing. Both the upper and low pump housings  120 ,  160  include radially protruding flanges  128 ,  162  that when mated together secure the diaphragm  140  there between. This configuration forms a fluid chamber  125  between the upper pump housing  120  and the diaphragm  140 . In this way, the inner surface of the upper pump housing  120  and the upper surface of the diaphragm  140  are the only portions of the pump  100  that should come in contact with the fluid. In contrast, a secondary chamber  165  is also formed between the lower pump housing  160  and the diaphragm  140 . Preferably, the secondary chamber  165  does not ever come in contact with the fluid. Additionally, the lower pump housing  160  preferably is adapted to be secured to a piston and vacuum assembly. The lower housing  160  preferably includes a coupling flange  168  that is designed to removeably seal with a piston housing. Thus, lower chamber  165  contains piston and vacuum forces capable of driving the diaphragm, which in turn moves fluid. 
         [0022]      FIG. 2  shows how the upper pump housing  120  is preferably installed as part of a fluid flow path in an intermediate location. A select fluid is input from a feed side  10  and pumped toward an outlet side  90 . Between those two ends  10 ,  90  are the pump  100 , valves  70  and other conduits and connectors, such as the T-connector  50  shown.  FIG. 3  shows an alternate embodiment of upper pump housing  121 , which provides more than one fluid port. Preferably, an inlet port  123  is coupled to the feed side and an outlet port  124  is coupled to the fluid destination.  FIG. 4  shows an embodiment similar to that shown in  FIG. 2 , but with a Y-connector  51 .  FIG. 8  shows an alternate embodiment of the upper pump housing  122 , with a variation of the coupling nozzle  116 . The nozzle  116  includes a hose barb connector  117  with a stop  119  to assist in hose or tubing installation and a notch  118  for placement of a compression component to secure the hose/tubing (not shown) in place during pump operation at high pressures. 
         [0023]    The diaphragm pump  100  cycles between drawing-in liquid and expelling liquid from its fluid chamber  125 . The diaphragm  140  is adapted to extend back and forth between the upper and lower chambers  125 ,  165 . As shown in  FIG. 5 , when secured to a piston assembly  200  that preferably includes a piston housing  220  with its own coupling flange  222 , a driven piston rod  210  and piston  205 , and one or more vacuum ports  164 ,  224 , the diaphragm  140  can be forced to deflect toward or away from the fluid port  110 . Preferably, at least one vacuum port  164 ,  224  is provided for depressurizing the lower chamber  165 . The piston housing  220 , along with the packed or sealed piston rod opening  225 , closes-off the lower chamber  165  and helps maintain an appropriate reduced pressure therein. The reduced pressure biases the diaphragm  140  to deflect toward that lower chamber  165 . The vacuum pressure, which is applied on the non-liquid side  165  of the pump, is preferably sufficient negative pressure to fill the upper housing chamber  125  with liquid fast enough to maintain the desired flow rate into the pump. 
         [0024]    Preferably, the piston  205  is designed to mechanically push the diaphragm  140  toward the fluid port  110 . When the pump assembly is coupled to fluid input and output lines through the upper coupling nozzle  115 , as the piston  205  retracts, diaphragm  140  moves from the upper chamber  125  toward the lower chamber  165 , biased by the vacuum forces, and preferably draws fluid into the upper chamber  125 .  FIGS. 1 and 5  shows the diaphragm  140  drawn toward the lower pump housing  160 . After the upper chamber  125  is filled with a fluid, as the diaphragm  140  is caused to move upward, preferably by the piston  205 , toward the fluid port  110 , the fluid is expelled through the fluid port  110 . For both drawing-in liquid to and expelling liquid from the pump  100 , the rate of the liquid flow can be controlled to achieve the desired conditions. 
         [0025]    In a preferred embodiment, the diaphragm pump  100  shown in  FIG. 1  is designed as a disposable unit for single or very limited use. The pump  100  preferably only has two elements (the upper housing  120  and the diaphragm  140 ) that ever come in contact with the handled fluid. Thus, by providing an easily removable pump housing  120 ,  160  along with its diaphragm  140  as a single unit, the contaminated parts can be changed-out after a single use. This prevents having to disassemble the pump, with the associated potential human or environmental exposure to process constituents, which in some cases may be hazardous. Even further, before use, as a single unit the pump housing  120 ,  160  along with its diaphragm  140  can be delivered assembled and sterilized (by gamma, chemical or moist heat processing) ready for use without the need to expose the fluid path to environment where it can be subject to microbial contamination. Both the upper pump housing  120  and the lower pump housing  160  can be made from inexpensive plastic, ceramic or metal materials designed for single or limited use, such as those discussed in 1997 Association of the Advancement of Medical Instrumentation Technical Information Report designated—TIR17-1997 (hereinafter referred to as “AAMI 1997”). In this way, the pump  100  is preferably disposed or discarded after it has been contaminated during use as a fluid handling element. It should be noted that references herein to the term “disposable” are to elements that are designed to be thrown away or discarded after a very limited number of uses and preferably a single use. The housings  120 ,  160  can be made formed by machining, stamping, molding or other known techniques for forming such items. 
         [0026]    Alternatively, only the upper housing  120  and the diaphragm  140  can be designed or intended for replacement, being the only contaminated parts in the pump  100 . Replacing them provides a quick and easy way to replace the pump assembly without taking time for cleaning in critical applications. Also, more of the assembly is re-usable by discarding only the contaminated portions. The upper pump housing  120  and the diaphragm  140  could either be separate or provided in a preassembled state. Either these two disposable elements can be bonded together or temporarily secured using tape or a clamp to hold them together. In this way, these two disposable elements  120 ,  140  can be added to the rest of the assembly and then secured using a sturdy, reuse-able clamp. As in the embodiments discussed earlier, the clamp is preferably suited to hold the pump together under normal operating pressures and vibrations. 
         [0027]    As mentioned above, the motion of the flexible diaphragm  140  draws-in and then expels the liquid in the upper pump chamber  125 . The diaphragm  140  is sealed between the upper and lower housings  120 ,  160  at the diaphragm coupling  130 . The flexible diaphragm  140  allows the pump to intake and expels liquid while maintaining a seal between two pump housings  120 ,  160 . The diaphragm is preferably made of a durable, flexible material such as silicone or thermoplastic elastomers, such as those given in AAMI 1997. Preferably, the diaphragm  140  is provided with a bulbous radial flange  142  that acts as a sealing ring when sandwiched between the upper and lower housings  120 ,  160 . Also, the diaphragm  140  can have a reinforced portion at its center  148 , as well as other portions (not shown) as desired. In a further preferred alternative embodiment, the diaphragm  140  can be reinforced with fabric or other materials, either embedded or joined to one side (such as the non-fluid-contact side), as might be suited to a particular application. 
         [0028]    The upper and lower coupling flanges  128 ,  162  can be secured using a contemporary sanitary clamp, tri-clamp or a locking collar (not shown). A clamp or collar can provide a simple mechanical means of securing and sealing the pump  100 . Preferably, the clamp or collar is made from similar durable but inexpensive materials to those of the upper and lower pump housings  120 ,  160 . Compatibility of materials for these different elements can ensure that all the parts of the pump  100  expand or contract in unison, as a result of temperature or pressure changes. 
         [0029]    In a further alternative embodiment, the pump  100  can be made integral with the flexible diaphragm  140 , providing a unitary element that is self-contained and easily added to or removed from a fluid handling assembly. To form such a unitary embodiment, the upper and lower sections of a pump housing  120 ,  160  could be ultrasonically bonded with the diaphragm  140  in place. Alternatively or additionally, the two flanges  128 ,  162  could be chemically bonded. 
         [0030]    The use of inexpensive clamps, collars or bonding techniques is particularly suited for a disposable or single use pump in accordance with the present invention. Because inexpensive materials and assembly techniques can be used to manufacture these elements, economies of scale can make it more cost effective and time efficient to use a new diaphragm pump  100 , than to clean and/or re-sterilize those parts for reuse. Cleaning, sanitizing or re-sterilizing a pump between uses involves significant down-time or delays between applications. In accordance with the present invention, the pump  100  is preferably pre-sterilized and delivered to the end user sterile and ready to use. Techniques such as gamma sterilization require large capital investments, and are not generally located on premises to the end-user. Thus, it is advantageous to perform the sterilization techniques during the assembly process and provide a relatively inexpensive product that can be disposed after a single or very small number of uses. With other pumps used in these processes such as rotary lobe pumps, product contact parts cannot be reasonably disposed of after used and some cannot be sterilized where sterilization creates a better quality process by eliminating microbial contamination from a fluid stream versus sanitization that only reduces microbial contamination. 
         [0031]    As will be recognized by one of skill in the art, many variations are possible and within the scope of this invention. For example, the pump  100  can be made to any convenient size, from relatively small bench top type systems to large, industrial scale pumping systems. The valve systems, conduit, and vessels described herein throughout can likewise be increased in size and/or capacity to provide pumping systems of various sizes and performance capabilities. 
         [0032]    When ready for use, the pump head  100  is preferably secured to the piston housing  200 . As with the coupling  130  of pump housings  120 ,  160 , the lower housing flange  168  can be secured to the piston housing flange  222  using a contemporary sanitary clamp, tri-clamp or a locking collar (not shown). Preferably, the piston housing securing mechanism is easily removable, so that pump  100  can be replaced when needed. Alternatively, in certain applications, it may be desired to sterilize the “piston” side of the diaphragm pump compartment. This could be done by autoclave, steam-in-place or other known techniques. This may be desirable if the pump used in a sterile process, such as a filtration process connected to a cell culture bioreactor, where an extra level of sterility assurance was desired. 
         [0033]    As shown in  FIGS. 6 and 7   a - c , a fluid flow path is generally provided from a feed side  10  and pumped toward an outlet side  90 . Between those two ends  10 ,  90  are one or more sets of fluid conduit  20 ,  80 , valves  70  and possibly other connectors. In one alternative embodiment of the current invention, the pump  100  is integrated into a single use flow path, including select conduit, connectors and/or valves. This fully integrated flow path configuration would preferably be sold to customers, assembled and even gamma-irradiated or ready to be sterilized by steam. The flow path could contain a large variety of components such as single use process containers (plastic/polymeric containers/bags), conduit, sensors, filters, and connectors. Thus, as described above, even when assembled in a complete integrated flow path, the connection of the lower pump housing  160  can be made to the piston housing  200  and vacuum system when ready for use. Similarly, the pump head  100  and corresponding flow path conduits could be removed at the end of the process and disposed of without exposing users to the process fluid. 
         [0034]    Numerous different valves  70  are available to suit particular applications. Automated valves, tubing pinch valves, or check valves (such as duck bill, ball, spring or flapper valves) can be used to allow liquid to flow into the pump head  100  from the feed side  10  during an intake cycle and prevent liquid from being drawn from the pump outlet  90 . Also, the valves  70  preferably prevent liquid, during a pump  100  expelling cycle, from being pumped from the pump head  100  back to the feed side  10  of the pump and only allow it to go toward the pump outlet  90 . The valves  70  could be integral to the pump head (not shown) or as shown in  FIGS. 2 and 6 , integrated into the conduit leading into  20  and out of  80  the pump head  100 . Alternatively, separate intake and outlet valves could be integrated into a special upper pump housing (not shown). In the case of automated valves, timing can be controlled by the pump control system  300 . 
         [0035]    When drawing fluid into the pump  100 , a feed side  10  valve is preferably open and an outlet side  90  valve is preferably closed. When expelling fluid from the pump, a feed side  10  valve is preferably closed and an outlet side  90  valve is preferably open. When such valves  70  are automated, in order to synchronize their timing, control equipment is generally employed. Preferably, the same control equipment  300  operating the pump process synchronizes the valves  70 . 
         [0036]    It should be noted that the upstream fluid conduit  20  (on the feed side of the pump  100 ) preferably does not need to withstand high pressures. In fact, it is preferred that the fluid flowing through the upstream conduit  20  only be at ambient pressure. While upstream pressure can be supplied to fill the pump head  100 , such is not necessary when using a vacuum on the non-liquid contact side of the pump assembly. In other words, the vacuum draws the diaphragm and correspondingly the fluid at the rate set by the piston. However, in contrast, the downstream fluid conduit  80  is preferably designed to withstand higher pump outlet pressures necessary for select filtration and chromatography applications. Thus, the downstream conduit  80  is preferably either reinforced or heavy gauge tubing, hose or pipe. It should be noted that references herein to the term “fluid conduit” or simply “conduit” are generally to elements capable of communicating fluid, such as tubing, hoses, pipes, or channels. It is understood that particular choices of conduit size, materials and design can be made to suit the application. 
         [0037]    As discussed above with regard to the materials used for the pump, container and connectors, it should be understood it is preferred that the couplings between the pump  100  should be inexpensive, reliable and easy to manipulate and secure. 
         [0038]    As shown in  FIGS. 6 and 7   a - c , a preferred embodiment uses a pump system with at least two “heads”  100  to deliver continuous flow. A combination of the two synchronized pumps avoids the intermittent flow rate generated by a single pump process. Each pump head  100  preferably cycles from a phase drawing liquid into its pump head, to a cycle expelling liquid from the pump head. Synchronizing the cycles of the two pump heads, generates a liquid flow rate that is relatively constant. The speed of the pistons would control the flow rate of liquid. Also, optimized pump head  100  and piston  205  sizes can achieve a wide range of flow rates and flow rate accuracies. A single head version of the pump described could also be made but it would deliver intermittent flow. 
         [0039]    As shown in  FIGS. 7   a - c , the pump requires a control system  300  to control the piston speed (flow rate) and to make sure the pump  100  is safe to use. The control system  300  may be a stand-alone, as part of the pump  100 , or may be integrated as part of a larger control system. A pressure sensor placed downstream of the pump (not shown) may be used to shut down the pump if pressure builds above a user defined set-point. Preferably, valves  75 , in combination with the control system  300 , direct the choice of one or more liquid input lines  10  from which the pump will draw. Also, the valves  75  can be automated on/off valves, such as automated diaphragm valves, controlling the selection of input liquid. Additionally, because the conduit assembly upstream of the pump  100  is preferably not pressurized, disposable hoses or tubing can be used in combination with automated pinch valves. Pinch valves are preferred for the upstream control system valves because disposable hoses or tubing can be quickly and easily loaded and unloaded. However, it is understood that the valves  75  could alternatively be manually actuated valves. 
         [0040]    It should be noted that the fluid can be a homogenous liquid, a composition of disparate fluids or one or more fluids combined with other solid matter. As mentioned above, the fluid is preferably drawn from one or more select feed/supply lines  10  into the diaphragm pump  100  and then expelled to one or more outlet lines  90  toward an intended destination. 
         [0041]    While various embodiments of the present invention are specifically illustrated and/or described herein, it will be appreciated that modifications and variations of the present invention may be effected by those skilled in the art without departing from the spirit and intended scope of the invention.