|Publication number||US3862886 A|
|Publication date||Jan 28, 1975|
|Filing date||Sep 20, 1973|
|Priority date||Sep 20, 1973|
|Publication number||US 3862886 A, US 3862886A, US-A-3862886, US3862886 A, US3862886A|
|Original Assignee||Limbro Chemical Co Inc|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (7), Referenced by (6), Classifications (16), Legal Events (5)|
|External Links: USPTO, USPTO Assignment, Espacenet|
United States Patent [1 1 Liner Jan. 28, 1975 1 1 STERILE PLATE COMPONENT PACKAGE FOR CULTURE GROWING APPARATUS  Inventor: John Liner, Woodbridge, Conn.
 Assignee: Limbro Chemical Co., Inc., New Haven, Conn.
 Filed: Sept. 20, 1973  Appl. No.: 398,983
 US. Cl 195/127, 206/303, 206/438,
206/456, 229/66  Int. Cl. Cl2b 1/04, Cl2k 1/10  Field of Search 195/142, 143, 127;
 References Cited UNITED STATES PATENTS 616,042 12/1898 Walsh 206/367 1,920,719 8/1933 Stich 195/142 1,930,300 10/1933 Ball 206/303 2,505,360 4/1950 Jel'l'reys 195/142 3,407,120 10/1968 Weiss et a1 195/142 3,594,277 7/1971 Muko i 195/143 3,680,953 8/1972 Ruhe 206/456 Primary Examt'rwr-William 1. Price Assistant E.\'aminer-Stephen P. Garbo Attorney, Agent, or FirmWulter Spruegel  ABSTRACT A sterile plate package providing a temporary plate unit in a disposable sealed wrapper, of which the unit provides a column of spaced plates slidahly received on a disposable arbor and releasahly held thereon hy resilient rings on the'arbor at the opposite ends of the column.
12 Claims, 7 Drawing Figures PATENIEDmaaxszs 3 862 886 Ill -1 j/ u ia'nIIIIIIIIIIIIiI I llllllllllllllll l V I 44' I W I i STERILE PLATE COMPONENT PACKAGE FOR CULTURE GROWING APPARATUS This invention relates to apparatus for growing tissue cultures in general, and to apparatus with replaceable sterile culture-adhering surfaces in particular.
The invention is concerned with growing cultures es pecially, though not exclusively, on a larger scale as re' quired for practical production of vaccines or to obtain the large quantities of virus required in research, for example. Prior culture-growing apparatus designed to that end provide culture-growing surfaces of large areas in the form of a column of spaced plates in an enclosing processing container, with the column of plates being assembled as a unit outside the container and as a unit placed in the container. This type of apparatus has proved to be highly practical for growing cultures on a large scale, but its performance in growing the intended pure cultures hinges on the imperative requirement of sterility of the plates which does involve the human element. Thus, assembly of the plates into a self-contained unit outside the container involves an attendants handling of the plates and, hence, requires subsequent sterilization of the entire unit for sterility of the plates, and the sterilized unit requires further manipulation by an attendant for its placement into the container, all of which may give rise to undetectable local contamination of the sterilized unit in the course of its handling even despite the average attendants devoted care to avoid any contamination.
It is a primary object of the present invention to provide apparatus of this type which has all the advantages of the aforementioned prior apparatus and, like the latter, features an insertable column of spaced culturegrowing plates in a processing container, but all handling of the plates, from their sterilization to their transfer into the container, which might conceivably give rise to their inadvertent contamination, is entirely eliminated.
It is another object of the present invention to provide apparatus of this type for which the culturegrowing plates are available in a sealed package in which they are enclosed and already preassembled in a sterile columnar unit, with this unit being transferred into a sterilized processing container by an attendant who simply breaks the package open and grasps the enclosed unit at the outside package for sliding the unit into the container all without the attendant touching any part of the unit or the interior of the container. With this arrangement, the attendant, who is preferably the one entrusted with the careful use of the apparatus for growing cultures, will certainly avoid any possible contamination of the plates and, moreover, need not at all be concerned with the task of sterilizing the plates, with this latter task being more appropriately undertaken by the supplier of the sealed packages whose operating methods and controls are necessarily geared for the ultimate in keeping the sterilized plates sterile in their packaging and in the shipment and storage of the sealed packages. Further, in having the sealed packages available when needed, apparatus of this type will lend themselves to virtually uninterrupted operation, for it takes very little time to replace the used plates in a processing container with a new column of sterile plates. Last, but not least, the above and also other advantages ensuing from the availability of the sealed packages speak strongly for reliance on these packed plates as disposable items after their one-time use, rather than go the time-consuming task of cleaning and sterilizing the column of used plates for their reuse.
it is a further object of the present invention to provide for apparatus of this type the aforementioned sealed package of sterile plates that are held in a temporary unit on a disposable center arbor from which they are releasable for slide-off in their columnar coordination after the outer package :is broken open, and the processing container has a center shaft with which the arbor is readily aligned and butted for slide of the plates in their columnar formation onto the shaft and into the container on their slide-off from the arbor, with the outer package and the arbor being then discarded. In arranging the sealed package in this fashion, the plates require merely simple center apertures for their hold on the arbor in the temporary unit and on the shaft in the processing container, and the plates may, by readily removable slip-on rubber bands or rings for example, be temporarily held in their columnar formation on the arbor, so that adequate endlengths of the latter beyond the plates serve particularly well for easy and contamination-free handling of the sterile plates in the process of their being packed and also for their transfer from the package into a processing container. Further, with the temporary columnar plate unit providing, in addition to the plates, only a minimum of the simplest and cheapest parts in the form of a disposable arbor and two rubber bands or rings, and the plates themselves being preferably molded plastic mass items of correspondingly very low cost, and with the outer package or wrapper being preferably and advantageously extruded plastic tubing, such as flexible polyethylene, for example, which is of exceedingly low cost and readily lends itself to quick and inexpensive heatsealing of its ends, the ensuing low cost of the sealed package to the user is all the more inducement to discard the plates after their one-time use.
Another object of the present invention is to provide apparatus of this type of which the processing container is of usual cylindrical form and is normally closed at both ends of which at least one end is formed by a removable end cover, and the aforementioned shaft is mounted in the other end of the container and extends axially to the opposite end thereof where it has a diametrically reduced end fittedly received in the closed end cover, and the arbor of the packaged temporary plate unit has at least one hollow end which, after breaking the outer package open, is telescoped with the reduced shaft end for transfer of the sterile plate column from the arbor onto the shaft. With this arrangement, the transfer of the sterile plate column from the package into the container is even further facilitated. Also, the plate column is preferably arranged, heightwise, to be clamped to the container ends on closure of the end cover so that there will be no possibility for disturbing endshake of the plates in a culturegrowing process, but equally important, the plates will turn with the container if the apparatus is in its operation turned horizontally for periodically dipping the plates and growing cultures thereon into nutrient media in the container.
A further object of the present invention is to provide the aforementioned outer wrapper of the sealed package of sterile plates in the preferred form of flexible tubing of which the sealed ends are prescored for simple tear-off of either one of the end seals to open the package, and the outer wrapper is sufficiently larger in circumference than the plates therein that the opened end of the wrapper may easily be slipped over the temporarily open container end. With this arrangement, the outer wrapper may conveniently be slipped over the container while the package is held in readiness or near-readiness for plate transfer into the container but in a disposition other than upright to delay plate transfer, whereupon the container and package are stood upright for gravity slide of the plates from the package into the container. In so doing, actual transfer of the plates from the package into the container takes place in virtually sealed-off fashion, and the outer wrapper will naturally spread or droop over the container and not bunch up to interfere with free sliding transfer of the plates from the package into the container.
Further objects and advantages will appear to those skilled in the art from the following, considered in conjunction with the accompanying drawings.
In the accompanying drawings, in which certain modes of carrying out the present invention are shown for illustrative purposes:
FIG. 1 is a side view of apparatus involving the invention;
FIG. 2 is an end view of the apparatus as seen in the direction of the arrow 2 in FIG. 1;
FIG. 3 is a side view of a prominent packaged apparatus component according to the invention;
FIG. 4 is an end view of the packaged apparatus component as seen in the direction of the arrow 4 in FIG. 3;
FIG. 5 is a view of the apparatus, including its packaged component, in the process of their assembly;
FIG. 6 is a fragmentary section through the apparatus taken substantially on the line 66 of FIG. 1; and
FIG. 7 is a side view at a reduced scale of a packaged apparatus component embodying the invention in a modified manner.
Referring to the drawings, and more particularly to FIGS. 1 and 2 thereof, the reference numeral 10 designates culture-growing apparatus having as its major operating components a container 12 and a column 14 of spaced plates 16 with opposite faces 18.
The container 12 is in this instance formed of an open-ended cylinder 20, and end covers 22 which close the cylinder 20 and of which at least one is removable for opening the container at one end. The cylinder 20 is of any suitable transparent material, such as plastic or glass, for example, and the end covers 22 are preferably identical and conveniently molded of any suitable plastic, with both end covers 22 being in this instance removable from the cylinder 20. As shown in FIG. 6, the end covers 22 are provided with center recesses 24 and continuing reduced bores 26 for the mount of a shaft 28 which in this instance forms part of the container 12. The end covers 22 are further provided with annular grooves 30 in which the ends of the cylinder 20 are received and seated against sealing rings 32 therein. The shaft 28 is with its opposite ends received in the center recesses 24 in the end covers 22 and seated against sealing rings 34 therein, and reduced threaded ends 36 of the shaft 28 extend through the bores 26 in the end covers 22 into threaded engagement with knobs 38 which are manually tightened to clamp'the parts 20, 22 and 28 together into the container 12.
The container shaft 28 serves in this instance also as the mount for the plate column 14. The plate column 14 is formed ofa plurality of center-apertured plates 16 of preferred disc form, and a plurality of apertured spacers 40 which are interposed between the plates, with these plates and-spacers being with their apertures slidably received on the shaft 28 to form the column 14 of spaced plates. The plates 16 may be of any material suitable or treatable for culture adherence to their opposite faces 18. In their preferred form, the plates 16 are of molded plastic with the spacers 40 formed integrally therewith (FIG. 6'). The plate column 14, while slidably received on the shaft 28, bears with its opposite ends against the end covers 22, and in this instance against center bosses 42 thereon, and is clamped against the latter by the tightened knobs 38 so that the plate column 14 is as a unit turnable with the container 12 when the latter is turned in an exemplary mode of operation described hereinafter.
The interior of the container 12 and the plate column 14 therein must be sterile for an operation of the apparatus. With the interior of the container and the plate column therein being sterile, the apparatus is prepared for a culture-growing cycle of operation by introducing into the container 12, through the then open filler hole 44 in one of the end covers 22 (FIG. 6), nutrient medium in liquid form with therein suspended live cells of desired concentration for planting, with the medium thus introduced filling the container only partly for a particular exemplary operation, whereupon the filler hole 44 is closed and sealed by a plug 46. For this particular operation, the container 12 is placed horizontally on driven rollers 48 (FIG. 2) which slowly turn the container and the plate column 14 therein, with the live cells in the liquid medium settling on the faces 18 of the plates 16 for tissue culture growth thereon, and these tissue cultures on the plates being by the turning container periodically dipped into the liquid medium for their proliferation on the plates. This is continued until a confluent layer of cells is attained on the faces 18 of the plates 16, with these cells being then available for various purposes such as vaccine production, biochemical production or nutritional observations. If these cells are used for vaccine production, for example, the nutrient medium is removed from the container 12 and replaced with a maintenance medium with which the particular virus is introduced for vaccine production in known manner.
After a concluded operation of the apparatus, the container 12, at least, must be cleaned and sterilized for the next operation of the apparatus, and the plates 16 must also be cleaned and sterilized if they are to be reused. While cleaning and sterilizing of the container 12 is a relatively simple task, the invention contemplates the elimination of the more involved and not always entirely reliable task of cleaning and especially sterilizing the plates 16 for their reuse, by making available packaged sterile plates which are disposable after their one-time use.
FIGS. 3 and 4 show a package 50 of sterile plates according to the invention. The package 50 has as its major components a temporary sterile plate unit 52 and an outer sealed wrapper 54. The plate unit 52 provides a plurality of plates 16 which may be identical with those of FIG. 6, and which are slidably received on an arbor 56 in the form of a plate column 14 in which the plates 16 are equally spaced by their exemplary integral spacers 40. The plate column 14 is held on the arbor 56 by retainers 60 of which at least one is removable for endwise slide-off of the plate column from the arher. Preferably and'conveniently, the retainers 60 are simple resilient rings which are stretched around the arbor 56, wherefore either one of them is removable from the arbor. The arbor 56 is of a length appreciably in excess of the height of the plate column 14, and the latter is located on the arbor 56 so that substantial endlengths 62 of the latter extend beyond the plate column 14. The arbor 56 is of any suitable material, preferably inexpensive plastic, and at least one endlength 62 thereof is hollow as at 64 (FIG. 4), with the arbor being preferably extruded in sleeve form so that both endlengths 62 thereof are hollow.
The outer wrapper 54 is preferably flexible, and in its preferred form is a tube of any suitable, preferably plastic material, such as extruded polyethylene, for example, having its opposite ends 66 flattened and suitably sealed, as by heat-sealing, for example, to form end seals 68. Conveniently, the ends of the tube are prescored as at 70 for ready tear-off of either end seal 68 to break the wrapper 54 open, i.e., open its end thereat. The tubular wrapper 54 is of a diameter larger than that of the plates 16, and preferably even larger than the diameter of the container 12 for a reason mentioned hereinafter, and the wrapper is also considerably longer than the arbor 56, so that the enclosed plate unit 52 is rather loose in the sealed wrapper 54.
In preparing the sterile plate package 50, plates 16 of the required number are assembled on an arbor 56, and resilient rings 60 applied to the arbor. The temporary plate unit 52 thus assembled is then sterilized conveniently as a unit, whereupon the sterilized unit 52 is placed into an open tubular wrapper 54 preferably by an attendants gloved hand on one of the exposed endlengths 62 of the arbor 56. The tubular wrapper 54 may also be pre-sterilized, though this is not absolutely necessary in proper handling of the wrapper in a clean environment. Once the sterilized plate unit 52 is introduced in the open tubular wrapper 54, the ends 66 of the latter are flattened and scored and sealed to form the tear-off end seals 68. This concludes the formation of the sterile plate package 50, and the same may be shipped and stored for use when needed, with the temporary plate unit 52 being kept sterile while the pack age remains sealed.
Assuming that an operation of the apparatus has been concluded, one of the end covers 22 of the container 12 is removed and the used plate column 14 stripped from the container shaft 28. The empty container 12 is then cleaned and sterilized preparatory for the next operation. An attendant will then resort to an available sterile plate package 50, and first tear off one of the end seals 68 of the wrapper 54 to open one end of the latter, and then remove the nearby resilient ring 60 from the arbor 56 and through the open wrapper end, preferably with the aid of a suitable sterile tool to avoid any touch by the attendant of any of the sterile plates. In then holding the torn end of the wrapper 54 open with one hand, and gripping the accessible endlength 62 of the arbor 56 at the other end of the wrapper with the thumb t and index finger i, for example, of the other hand, not directly but through the surrounding wrapper end (FIG. 5), the attendant will have adequate support of the package to lead the open end of the wrapper over the open end of the container 12 and align the exposed end of the arbor 56 with, and butt it against, the adjacent end of the container shaft 28, all while the container and package are held in a disposition other than upright to prevent slide-off of the plate column 14 from the arbor 56 onto the container shaft 28. Alignment of the exposed arbor end with the adjacent end of the container shaft 28 for subsequent transfer of the plate column 14 from the arbor 56 onto the shaft 28 is greatly facilitated by the hollow condition of this exposed arbor end which permits ready telescoping of the latter with the adjacent reduced end 36 of the shaft 28 to thus temporarily lock the exposed arbor end in accurate alignment with the adjacent shaft end. Having once led the open wrapper end over the open container end and telescoping the exposed arbor end with the adjacent end of the container shaft 28, the attendant simply manipulates the container and package into an upright disposition (FIG. 5) in which the sterile plate column 14 will freely slide from the arbor 56 onto the shaft 28 in the container 12, whereupon the arbor 56 and wrapper 54 are discarded. Transfer of the plate column 14 from the arbor 56 onto the container shaft 28 will take place in virtually sealed-off fashion due to the droop of the open wrapper end over the open end of the container (FIG. 5), and the entire transfer of the sterile plate column 14, from opening the package to slide-off of the plate column from the arbor onto the container shaft, takes place without human touch of any of the sterile plates or other exposure of the latter to any possible contamination. Once the new sterile plate column 14 is transferred into the container 12 in this or a similar fashion, the latter is closed by reapplying the end cover 22, and the apparatus is then ready for a next operation.
While the package 50 with a plurality of sterile plates is highly advantageous for growing cultures on a larger scale, it is fully within the purview of the invention to provide such a package with fewer plates and even with a single plate. Thus, FIG. 7 shows a modified package 50a of which the sealed wrapper 54a contains a temporary sterile plate unit 52a with but one plate 16a. The package 50a may in all other respects be like the package 50 of FIGS. 3 and 4, with the tubular wrapper 54a having the tear-off end seals 68a, and the plate 16a with the integral spacers 40a being retained on an arbor 56:: by removable resilient rings 60a. The package 50a may be for use with a container which may be similar to the container 12 except that it is preferably much shorter to accommodate the single plate l6a.
What is claimed is:
1. A plate component package for a processing container of culture-growing apparatus, comprising a temporary sterile plate unit having a plurality of plates with center apertures and opposite faces for culture adherence, a plurality of apertured spacers, an arbor on which said plates and spacers are slidably received with their apertures and with the spacers interposed between the plates to form a column of spaced plates, and retainers on said arbor at the opposite ends of said plate column for holding the latter on said arbor, with at least one of said retainers being removable from said arbor for slide-off of said plate column from said arbor, and said arbor having an endlength extending beyond the other of said retainers; and a sealed wrapper enclosing said plate unit, and being breakable for removal of said one retainer and plate column from said arbor and wrapper.
2. A plate component package as in claim 1, in which said plates are identical discs, and said spacers are integral parts of said discs.
3. A plate component package as in claim 2, in which said retainers are resilient rings stretched around said arbor.
4. A plate component package as in claim 2, in which said wrapper is flexible and of sufficient volume to permit shake of the enclosed plate unit therein in all directions.
5. A plate component package as in claim 4, in which said arbor endlength is sufficiently long to be manually grippable for holding said plate unit thereat, and said wrapper is distortable against said arbor endlength for manually gripping the latter through said wrapper.
6. A plate component package as in claim 2, in which said wrapper is a flexible tube in which said plate unit extends axially, with said tube being of uniform diameter larger than that of said discs, and of a length greater than that of said arbor, and the ends of said tube being flattened and sealed thereat for sealing the wrapper, with either sealed end being breakable to open the tube thereat.
7. A plate component package as in claim 6, in which said tube is of plastic, and said sealed ends thereof are prescored for tear-off of either sealed end from the tube.
8. A plate component package as in claim 6, in which the diameter of said tube is sufficiently large to pass the opened end thereof over a processing container.
9. A plate component package for a culture processing container having a plate support shaft with a reduced end, comprising a temporary sterile plate unit having a plurality of plates in disc form with center apertures and opposite faces for culture adherence, a plurality of apertured spacers, an arbor on which said plates and spacers are slidably received with their apertures and with the spacers interposed between the plates to form a column of spaced plates, and retainers on said arbor at the opposite ends of said plate column for holding the latter on said arbor, with at least one of said retainers being removable from said arbor for slide-off of said plate column from said arbor; and a sealed wrapper enclosing said plate unit and being breakable to open said wrapper for removal of said one retainer, and'plate column from said arbor and wrapper, with the end of said arbor adjacent said one retainer being hollow and adapted, when accessible through the opened wrapper, to telescope with the reduced shaft end in a processing container for transfer of the plate column onto the shaft.
10. A plate component package as in claim 9, in which said arbor has-opposite endlengths beyond the respective retainers thereon and sufficiently long that either endlength is manually grippable for holding said plate unit thereat, and said wrapper is a flexible tube in which said plate unit extends axially, with said tube being of uniform diameter larger than that of said plates, and of a length greater than that of said arbor, and the ends of said tube being flattened and sealed thereat for sealing the wrapper, with either sealed end being breakable to open the tube thereat, and said wrapper being distortable against either of said arbor endlengths for manually gripping the latter through said wrapper.
11. A plate component package as in claim 10, in which each of said retainers is removable from said arbor, and each arbor end is hollow.
12. A plate component package for a processing container of culture-growing apparatus, comprising a temporary sterile plate unit having at least one plate in disc form with a center aperture and opposite faces for culture adherence, at least two apertured spacers, an arbor on which said plate and spacers are slidably received with their apertures, and with the spacers on opposite sides of the plate and formingwith the latter a transfer pack, and retainers on said arbor at the opposite ends of said transfer pack for holding the latter on said arbor, with at least one of said retainers being removable from said arbor for slide-off of said transfer pack from said arbor, and said arbor having an endlength extending beyond the other of said retainers; and a sealed wrapper enclosing said plate unit, and being breakable for removal of said one retainer and transfer pack from said arbor and wrapper.
|Cited Patent||Filing date||Publication date||Applicant||Title|
|US616042 *||Jul 11, 1898||Dec 13, 1898||Ralph walsh|
|US1920719 *||Jan 9, 1932||Aug 1, 1933||Stich Eugen||Aerating device|
|US1930300 *||Nov 11, 1931||Oct 10, 1933||Chicago Belting Company||Display container|
|US2505360 *||Jul 8, 1943||Apr 25, 1950||Isabel H Jeffreys||Fungus enzyme production|
|US3407120 *||Dec 23, 1965||Oct 22, 1968||Abbott Lab||Tissue culture propagator and method|
|US3594277 *||Apr 23, 1968||Jul 20, 1971||Atlantic Richfield Co||Process for fermenting hydrocarbons|
|US3680953 *||Nov 26, 1969||Aug 1, 1972||Bosch Photokino Gmbh||Slide projector and tray therefor|
|Citing Patent||Filing date||Publication date||Applicant||Title|
|US4061134 *||Oct 28, 1975||Dec 6, 1977||Samuels Peter B||Arterial graft device|
|US4734373 *||Jun 24, 1986||Mar 29, 1988||Bartal Arie H||Apparatus for enhancing cell growth, preservation and transport|
|US6415921 *||Sep 30, 1999||Jul 9, 2002||Advanced Cardiovascular Systems, Inc.||Apparatus to prevent radiation source delivery device from being contaminated during brachytherapy procedure|
|DE3413707A1 *||Apr 12, 1984||Oct 17, 1985||Skoda Rastislav Dr Med Vet||Process for the mass cultivation of cells in lamellar chambers|
|EP0569753A2 *||Apr 23, 1993||Nov 18, 1993||Doverton Ltd.||Device for receiving, storing and dispensing plates with bound biologically active substances|
|EP1304370A1 *||Oct 22, 2001||Apr 23, 2003||Integra Biosciences Holding AG||Insert for rotatable bottle|
|U.S. Classification||435/299.1, 206/438, 206/456, 383/209, 435/810, 206/303|
|Cooperative Classification||C12M23/32, C12M23/28, Y10S435/81, C12M25/06, C12M23/14|
|European Classification||C12M23/28, C12M23/14, C12M23/32, C12M25/06|
|Dec 11, 1990||AS||Assignment|
Owner name: FIRST CITY, TEXAS-HOUSTON, N.A., 1001 MAIN STREET,
Free format text: SECURITY INTEREST;ASSIGNOR:FLOW LABORATORIES, INC., A MD CORP.;REEL/FRAME:005554/0153
Effective date: 19901130
|Nov 15, 1989||AS||Assignment|
Owner name: FLOW LABORATORIES, INC., CONNECTICUT
Free format text: MERGER;ASSIGNOR:LINBRO SCIENTIFIC, INC., (MERGED INTO);REEL/FRAME:005182/0826
Effective date: 19801120
|Nov 15, 1989||AS03||Merger|
Owner name: FLOW LABORATORIES, INC., NEW HAVEN, CT A CORP. OF
Owner name: LINBRO SCIENTIFIC, INC., (MERGED INTO)
Effective date: 19801120
|Nov 13, 1989||AS06||Security interest|
Owner name: FIRST CITY, TEXAS-HOUSTON, N.A., 1001 MAIN, HOUSTO
Owner name: FLOW LABORATORIES, INC.
Effective date: 19891108
|Nov 13, 1989||AS||Assignment|
Owner name: FIRST CITY, A NATIONAL BANKING ASSOCIATION, TEXAS
Free format text: SECURITY INTEREST;ASSIGNOR:FLOW LABORATORIES, INC.;REEL/FRAME:005194/0930
Effective date: 19891108