Abstract:
Disclosed is a system for dispensing and supplementing a large volume of liquid for use with cell and tissue cultures. The system disclosed comprises a large volume drum having liquid contained therein. The system disclosed further comprises a first assembly for dispensing the liquid from the large volume drum. The system disclosed further comprises a second assembly for supplementing the first liquid contained in the large volume drum with the second liquid. The system disclosed may also comprise a third mechanical arrangement for mixing the first and second liquids.

Description:
BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The present invention relates generally to liquid dispensing systems. More particularly, the present invention relates to a dispensing and supplementation system for large volumes of various liquids for use with cell and tissue cultures. 
     2. Related Art 
     Scientists and technicians working in the biotechnology sciences often require the use of liquid media for use with cell and tissue cultures. To obtain the most cost effective and efficient results with cell and tissue culture, it is often desirable to use large volumes of liquid media for a given experiment or process. 
     One such system is manufactured by JRH BioSciences, Inc. This system consists of a well bucket having a plastic bag mounted therein. The plastic bag has one port with one associated fluid line attached thereto. The liquid media contained within the bag can only be dispensed. 
     Another type of liquid dispensing system is that referred to as a &#34;STAK PACK&#34; design. The STAK PACK system comprises a plurality of individual liquid containers that can be serially attached to create a large multiple unit fluid system. The liquid media can be dispensed via a dispensing port and filled via a filling port. 
     Conventional systems of the type described above have several disadvantages. First, conventional systems can typically only provide small volumes of liquid media. Small volume liquid media systems become present significant problems when attempting to prepare or diagnose certain types of cell and tissue cultures. 
     Second, conventional systems can only dispense the liquid media and do not offer the user the ability to supplement the liquid media. In diagnostic testing and preparation, it is often advantageous to modify the working liquid media fluid so that variations can be experimented with. The ability to supplement as opposed to preparing a new solution is a significant advantage to people working in the biotechnology industry. 
     Third, conventional systems typically have only one dispensing port. In systems of this type, the user must adapt their internal distribution systems to that of the dispensing systems. This is a significant disadvantage. 
     SUMMARY OF THE INVENTION 
     The system of the present invention is particularly adapted to handle large volumes of various liquids for use with cell and tissue cultures. The system of the present invention generally comprises a large volume drum containing a first liquid, means for dispensing the first liquid from the large volume drum, and means for supplementing the first liquid contained in the large volume drum with a second liquid. Further provided in the system of the present invention is means for uniformly mixing the first and second liquids. 
     The dispensing means generally comprises a dispensing cap attached to the large volume drum. The dispensing cap comprises an internal dispensing port and an external dispensing port. The internal dispensing port and the external dispensing port are in communication with each other. The dispensing cap further comprises an internal sampling port and an external sampling port. The internal sampling port and the external sampling port are in communication with each other. 
     The dispensing means further comprises an internal dispensing line connected to the internal dispensing port and an external dispensing line connected to the external dispensing port. The internal dispensing line and the external dispensing line carry the liquid from the drum to the external source. Additionally, the external and internal dispensing line provides a means to initially fill the drum. 
     The dispensing means further comprises an internal sampling line connected to the internal sampling port and an external sampling line connected to the external sampling port. The internal sampling line and the external sampling line are provided such that the end user may sample small volumes of the liquid contained in the drum. 
     The supplementing means generally comprises a supplementation cap that is attached to the drum. The supplementation cap generally comprises an internal supplementation port and external supplementation port. The internal and external supplementation ports provide communication between the inside of the drum and the external environment. 
     The supplementing means further comprises an internal supplementation line connected to the internal supplementation port and an external supplementation line connected to the external supplementation port. The internal supplementation line and the external supplementation line provide the mechanism that carries the supplement liquid into the drum from the external source. 
     The mixing means generally comprises the dispensing means and supplementation means heretofore described. In the mixing mode, the external dispensing line is connected with the external supplementation line. Thereafter conventional pumping apparatus is applied to the system to generate a fluid circulation from the bottom of the drum to the top of the drum. This circulation results in the supplement liquid being mixed with the original liquid. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     Various objects, features and attendant advantages of the present invention will be more fully understood from the following detailed description of the present invention when considered in connection with the accompanying drawings, in which: 
     FIG. 1 is a partial cut-away, perspective view of the preferred of the present invention; 
     FIG. 2 is a detailed view of the drum; 
     FIG. 3 is a detailed view of the dispensing assembly; 
     FIG. 4 is a detailed view of the supplementation assembly; 
     FIG. 5 is shows the mixing embodiment of the present invention; and 
     FIG. 6 is a detailed view of the dispensing cap. 
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     The present invention is an integrated dispensing and supplementation system. The system and method of the present invention allows for the sterile dispensing and supplementation of large volumes of various liquids for cell and tissue cultures. As will be more fully understood from the following detailed description, the present invention has the ability to dispense and supplement through normal distribution environments and is manufactured using conventional components. The system of the present invention can provide scientists and technicians large scale volumes of various liquids heretofore unavailable in conventional dispensing systems. 
     Referring first to FIG. 1, the system of the present invention comprises a drum 110, a dispensing assembly 120, and a supplementation assembly 130. Drum 110, as will be more fully described herein, is generally provided to contain large scale volumes of various liquids for cell and tissue cultures. 
     Dispensing assembly 120, as will be more fully described herein, generally functions to dispense the liquid contained within drum 110 to an outside external source. Such outside external source may be that of cell testing apparatus. Dispensing assembly 120 is designed to offer several ways of dispensing the liquid contained in drum 110. In one dispensing mode, dispensing assembly 120 provides high volume dispensing. In another dispensing mode, dispensing assembly 120 provides low volume dispensing. Low volume dispensing, for example, may be required when the liquid media in drum 110 need only be sampled. 
     Supplementation assembly 130, as will be more fully described herein, generally functions to supplement the liquid contained in drum 110. Supplementation assembly 130 allows the user to add a variety of liquids to the original liquid contained in drum 110. The ability to supplement large scale volumes of the original liquid contained in drum 110 is a significant advantage in diagnostic testing and batch processing. 
     As will be described in more detail herein, the present invention also provides a feature wherein the supplement added via the supplementation assembly 130 can be uniformly mixed with the original liquid. This feature is generally achieved by connecting the dispensing assembly 120 to the supplementation assembly 130. 
     Referring next of FIG. 2, drum 110 generally comprises a body 205, a dispensing port 210 and a supplementation port 215. Dispensing port 210 is provided so that the dispensing assembly 130 may be securely and sealably attached thereto. Dispensing port 210 is sometimes referred to as a bung hole. In the preferred embodiment, dispensing port 210 is formed as part of body 205 and has buttress grooves 220. 
     Supplementation port 215 is provided so that supplementation assembly 130 may be securely and sealably attached thereto. Supplementation port 215 has standard National pipe thread (NPT) grooves 225. Like dispensing port 210, supplementation port 215 is formed as a part of body 205. 
     Drum 110 of the preferred embodiment is made from plastic. A plastic material is preferred so that the liquid is chemically compatible. Drum 110, however, can be other materials such as metal. If a metal material is used, drum 110 should be lined with a suitable material to ensure chemical compatibility. 
     Drum 110 of the preferred embodiment has a 55-gallon volume capacity. Drum 110, however, may be designed to contain a smaller or larger volume of liquid. Drum 110 may also be designed to contain liquids other than those used for cell and tissue culture applications. 
     As shown in FIG. 3, dispensing assembly 120 first comprises a dispensing cap 302. As will be more fully discussed herein, dispensing cap 302 is custom designed to have several ports (not shown) which provide various functions and features. In the preferred embodiment, these ports are for dispensing high volumes of liquid media, sampling small volumes of liquid media, and for venting the internal compartment of the drum 110. 
     Dispensing cap 302 is designed to attach via buttress threads 304 to dispensing port 210 of drum 110. Dispensing cap 302 further comprises a gasket 305. Gasket 305 is provided so that dispensing cap 302, when fastened, will be in sealable contact with dispensing port 210 of drum 110. Gasket 305 is of conventional design and readily available from a variety of manufacturers. 
     Dispensing assembly 120 further comprises an internal sampling line 306. Internal sampling line 306 has a first end 307 and a second end 311. Internal sampling line 306 is provided to carry liquid from the bottom of drum 110 through the dispensing cap 302 and to an external sampling line 322 (to be described). Sampling line 306 of the preferred embodiment is made of flexible 1/4 inch tubing. It should be readily apparent, however, that sampling line 306 can be made in a variety of sizes and from a variety of materials. Choice of size may depend on the quantity of material to be sampled and the sampling device to be used. Choice of material should be limited to materials that will not contaminate the liquid. 
     Internal sampling line 306 is connected to the sampling port (not shown and to be described) of dispensing cap 302 via a barbed bulkhead fitting 308. Bulkhead fitting 308 is formed with threads 309 that screwably connect with corresponding threads in the internal sampling port (not shown) of dispensing cap 302. To ensure that internal sampling line 306 is securely fastened to bulkhead fitting 308, a tie wrap 310 is attached around internal sampling line 306. 
     Bulkhead fitting 308 is of conventional barbed design. As should be readily apparent, however bulkhead fitting 308 may be chosen from a variety of interconnect configurations. 
     Internal sampling line 306 further has attached a glass rod 312. Glass rod 312 is frictionally fit into the second end 311 of sampling line 306. Glass rod 312 is provided to thereby maintain the position of sampling line 306 at the bottom of drum 110. Because internal sampling line 306 is made of a plastic material, internal sampling line 306 may tend to float within the liquid. 
     Glass rod 312 is of conventional design. Glass rod 312, however, may be made from material other than glass, such as metal. Care must be taken to ensure that the chosen material will not contaminate the liquid. 
     Dispensing assembly 120 further comprises an internal dispensing line 314. Internal dispensing 314 has a first end 315 and a second end 317. First end 315 of internal dispensing line 314 is connected to the barbed end of a bulkhead fitting 316. Bulkhead fitting 316 is securely attached to the internal dispensing port (not shown) of dispensing cap 302. Internal dispensing line 314 is provided to carry high volumes of liquid from drum 110. Internal dispensing line 314 is securely attached to the barbed end of bulkhead fitting 316 using a tie wrap 318. 
     Dispensing assembly 120 further comprises a glass rod 320. Glass rod 320 is frictionally fitted to the second end 317 of internal dispensing line 314. Glass rod 320, like glass rod 312, is provided to ensure that internal dispensing line 314 remains positioned substantially at the bottom of drum 110. 
     As can be seen from the above discussion, internal sampling line 306 and internal dispensing line 314 are positioned within drum 110. Furthermore, internal sampling line 306 and internal dispensing line 314 of the preferred embodiment are of the same length and the same type of flexible tubing. In addition, internal sampling line 306 and internal dispensing line 314 are designed to have a length such that the lower end of glass rods 312 and 320 will be substantially at the bottom of drum 110. 
     As also shown in FIG. 3, dispensing assembly 120 further comprises an external sampling line 322. First end 323 of external sampling line 322 has a first end 323 and a second end 325. First end 323 of external sampling line 322 is connected to dispensing cap 302 via a bulkhead fitting 324. External sampling line 322 is connected to the barbed end of bulkhead fitting 324 and securely fastened thereto using a tie wrap 329. 
     As also shown in FIG. 3, further attached to the second end 325 of sampling line 322 is a male luer adapter 326. Male luer adapter 326 is attached to the second end 325 of external sampling line 322 via a tie wrap 327. As will be shown herein, male luer adapter 326 is provided so that the user may have an optional method of sampling the liquid. As will also be discussed, it is possible for the user to supplement liquid media via male luer adaptor 326. Male luer adapter 326 is of conventional design and can be readily purchased from a variety of manufacturers. 
     Also shown attached to male luer adapter 326 is a septum 328. Septum 328 is removably connected to male luer adaptor 326. Septum 328 is of conventional design and is provided so that sampling of the liquid media contained in drum 110 may be performed using a syringe or the like. A cap 330 is provided on septum 328 so that septum 328 will not become contaminated. 
     As also shown by FIG. 3, dispensing assembly 120 further comprises an external dispensing line 332. External dispensing line 332 provides the primary method of dispensing high volumes of liquid from the drum 110. External dispensing line 332 has a first end 333 and a second end 335. The first end 333 of external dispensing line 332 is connected to dispensing port 302 via a bulkhead fitting 334. First end 333 of external sampling line 332 is securely fastened to the barbed end of bulkhead fitting 334 using a tie wrap 336. 
     Attached to the second end 335 of external dispensing line 332 is a female connector 338. Female connector 338 is provided so that the user may connect the primary dispensing system. Connector 338 is securely fastened to the second end 335 of external dispensing line 332 using a tie wrap 340. 
     Female connector 338 is of conventional interconnect design. Female connector 338, however, may embody other interconnect configurations as long as it is compatible with the mating connector to be used by the end user. 
     Further shown is an auxiliary external dispensing line 342. Auxiliary external dispensing line 342 is generally provided to allow the user to fill the drum 110. 
     Auxiliary external dispensing line 342 has a first end 343 and a second end 345. Auxiliary external dispensing line 342 has attached at the first end 343 a male connector 344. Male connector 344 is secured to first end 343 of auxiliary external dispensing line 342 using a tie wrap 346. 
     Male connector 344 of auxiliary external dispensing line 342 is removably connected with female connector 338 of external dispensing line 332. However, the female connector 338 and male connector 344 assembly is enclosed by heat-shrinkable wrap 348. Heat-shrinkable wrap 348 can be removed by the user such that male connector 344 and female connector 338 may be engaged and disengaged as required by the user. A flow clamp 352 is shown attached to external dispensing line 332. Flow clamp 352 is generally provided so that the flow of fluid through external dispensing line 332 can be stopped by a user. Flow clamp 352 operates by pinching external dispensing line 332. 
     Attached to the second end 345 of auxiliary external dispensing line 342 is a protective cap 350. Protective cap 350 ensures that no contaminants enter auxiliary external dispensing line 342. 
     When filling is desired, the end user removes the protective cap 350 and suitably fills the drum 110 with liquid media. After filling is complete, auxiliary external dispensing line 342 is closed off. Thereafter, auxiliary dispensing line 342 remains connected to the dispensing assembly 120 as a protective device only. 
     As also shown by FIG. 3, dispensing assembly 120 further comprises a venting line 354. Venting line 354 is provided so that the pressure within drum 110 will always remain at atmospheric conditions. Venting line 354 has a first end 355 and a second end 357. Venting line 354 is connected to dispensing port 302 via a bulkhead fitting 356. First end 355 of vent line 354 is securably attached to the barbed end of bulkhead fitting 356 using a tie wrap 358. 
     As also shown in FIG. 3, attached to the second end 357 of vent line 354 is an air filter 360. Air filter 360 is provided to ensure that no contaminants enter drum 110 via vent line 354. Air filter 360 is also used to maintain sterility of air venting in and out of the drum 110. 
     Air filter 360 is of conventional design and in the preferred embodiment has a porosity of 0.20 microns. Air filter 360 is a two-way hydrophobic filter and should be kept dry for optimum performance. 
     Air filter 360 has a barbed end 364 which is adapted to receive a protective cap 368. Protective cap 368 is provided so that no contaminants may unnecessarily enter air filter 360. 
     Air filter 360 further has a barb fitting 362. Barb fitting 362 is provided so as to receive one end of vent line 354. Vent line 354 is securably attached to barb fitting 362 of air filter 360 using a tie wrap 366. 
     As shown in FIG. 4, supplementation assembly 130 generally first comprises a supplementation cap 402. A flow clamp 351 is shown attached to vent line 354. Supplementation cap 402 securely mounts into supplementation port 215 of drum 110. Supplementation cap 402 is of conventional design and can be purchased from Rieke Corporation. 
     Supplementation cap 402 has an inlet port 432 and an outlet port 434 which are in communication with each other. Also provided is a gasket 403 which ensures good sealed contact between supplementation cap 402 and supplementation port 210 of drum 110. 
     Supplementation assembly 130 further comprises an internal supplementation line 404. Internal supplementation line 404 is generally provided to supplement (add) various liquids to the liquid of drum 110 as desired by the end user. Internal supplementation line 404 has a first end 405 and a second end 407. The first end 405 of internal supplementation line 404 is attached to supplementation cap 402 using a bulkhead fitting 406. Bulkhead fitting 406 of the preferred embodiment is of a one-piece design and, as shown in FIG. 4, has two ends 409 and 411. Ends 409 and 411 are barbed. Inlet port 432 is formed through end 411 of bulkhead fitting 406. Outlet port 434 is formed through end 409 of bulkhead fitting 406. 
     As shown, the first end 405 of internal supplementation line 404 is attached to barbed end 409 of bulkhead fitting 406 using a tie wrap 408. 
     Supplementation assembly 130 further comprises an external supplementation line 410. External supplementation line 410 has a first end 413 and a second end 415. Like internal supplement line 404, first end 413 of external line 410 is attached to the barbed end 411 of bulkhead fitting 406 using a tie wrap 414. 
     The second end 415 of external supplementation line 410 is attached to a male connector 416. The second end 415 of external supplementation line 410 is secured to male connector 416 using a tie wrap 418. Male connector 416 provides an interconnect area for the user to connect to so that they may supplement the liquid in the drum 110. 
     As also shown by FIG. 4, supplementation assembly 130 further comprises an auxiliary external supplementation line 420. Auxiliary external supplementation line 42D has a first end 425 and a second end 427. First end 425 of auxiliary external supplementation line 420 is connected to a female connector 422 and secured using a tie wrap 424. Female connector 422 is removably connected with male connector 416. 
     The female connector 422 and male connector 416 assembly is enclosed by heat-shrinkable wrap 426. Heat-shrinkable wrap 426 can be removed by the end user so that female connector 422 and male connector 416 can be disengaged, thereby allowing the end user access to supplement drum 110 via male connector 416. 
     As also shown by FIG. 4, the second end 427 of auxiliary external supplementation line 420 has connected thereto a protective cap 428. Protective cap 428 ensures that no contaminants from the environment enter the auxiliary external supplementation line 420 and thus drum 110. 
     Further shown in FIG. 4 is a flow clam 430. Flow clamp 430 is shown attached to external supplementation line 410. Flow clamp 430 is generally provided so that the flow of fluid can be stopped. Flow clamp 430 in operation pinches or shuts off external supplementation line 410. Flow clamp 430 should be clamped whenever supplementation assembly 130 is not in operation. 
     Heretofore, the present invention has been discussed in terms of either dispensing or supplementing. FIG. 3 shows an embodiment wherein the liquid media within drum 110 can be dispensed via dispensing line 332 or via sampling line 322. FIG. 4, as discussed, shows how the user may supplement the liquid media within drum 110 via supplementation assembly 130. 
     Another significant feature of the present invention is that of mixing. In other words, after supplementation, the user may mix the supplement liquid and the liquid originally contained in drum 110. Mixing of the supplement liquid with the original liquid is necessary so that a uniform composition can be achieved. 
     Referring now to FIG. 5, the mixing embodiment of the present invention is illustrated in more detail. As shown by FIG. 5, connector 416 has been disengaged from connector 422 of auxiliary supplementation line 420. Likewise, connector 338 of external dispensing line 332 has been disengaged from connector 344 of auxiliary dispensing line 342. 
     In the mixing embodiment, the user may connect male connector 416 with female connector 338. Upon engagement of male connector 416 and female connector 338, a communication loop between the bottom of drum 110 and the top of drum 110 is established. As can readily be seen, upon application of an external pumping action (not shown), the liquids contained within drum 110 will be caused to circulate from the bottom of the drum 110 to the top of the tank. This circulation action ensures that the supplemented liquid is fully mixed with the original liquid contained within drum 110. 
     As shown in FIG. 6, dispensing cap 302 comprises an internal sampling port 602, an internal dispensing port 604, an external sampling port 606, an external dispensing port 608, and a venting port 612. 
     Internal sampling port 602 is in communication with external sampling portion 606 to thereby provide access from the inside of drum 110 to the external environment. As discussed before, internal bulkhead fitting 309 connects to internal supply port 602, while bulkhead fitting 324 connects to external sampling port 606. 
     Dispensing cap 302 has also formed buttress threads 614. Buttress threads 614 are designed such as to mate with the corresponding buttress threads on the dispensing port 210 of drum 110. 
     The following will be a discussion of the preferred operation of the present invention. When filling the system of the present invention, protective cap 350 is removed. Thereafter, an external filling bell (not shown) is attached to second end 345 of auxiliary external dispensing line 342 to thereby insert the liquid to be filled. The filled liquid passes through the male connector 344/female connector 338 connection, down through external dispensing line 332, through dispensing cap 302, down internal dispensing line 314 and into drum 110. 
     Thereafter, the external dispensing line 332 is pinched or closed such that no other liquid can be added via auxiliary external dispensing line 342. Thereafter, the end user may either directly dispense the liquid that was filled into drum 110 or they may supplement with a second liquid. 
     If direct dispensing is desired, the end user will remove heat shrinkable wrap 348 and disengage male connector 344 from female connector 338. Thereafter, female connector 340 can be connected by the end user to an appropriate external device such as a reaction vessel. 
     If the user, however, desires to supplement the liquid contained in drum 110, they will remove heat shrinkable wrap 426 from supplementation assembly 130. Thereafter, the end user will disengage female connector 422 from male connector 416. This disengagement allows the end user to connect an appropriate supplementing means (not shown) to female connector 416. The supplemented liquid flows through female connector 416, down external supplementation line 410, through supplementation cap 402 and down internal supplementation line 404 into drum 110. 
     At this point, the original fluid in drum 110 has been supplemented with a second fluid. Thereafter, the end user may either dispense the first and second fluid as pending and as previously discussed in the prior dispensing discussion, or they may initiate the mixing mode of the present invention. 
     In the mixing operation, the end user connects female connector 338 of dispensing assembly 120 to male connector 416 of the supplementation assembly 130. Upon application of an external pumping action by a suitable pumping apparatus (not shown), the liquid at the bottom of tank 110 is caused to be recirculated to the top of tank 110. Finally, it should also be noted that whenever the system of the present invention is not in operation, flow clamps 430 and 352 should be tightened to thereby prevent contaminants from entering drum 110. 
     The foregoing description is intended primarily for purposes of illustration. The present invention may be embodied in other forms or carried out in other ways without departing from the spirit and scope of the invention. Modifications and variations still falling within the spirit and scope of the present invention will be readily obvious to those skilled in the art.