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WO1988001605A1 - Contamination-proof stopper, in particular screw cap, for cell culture bottles - Google Patents

Contamination-proof stopper, in particular screw cap, for cell culture bottles Download PDF

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Publication number
WO1988001605A1
WO1988001605A1 PCT/EP1987/000468 EP8700468W WO8801605A1 WO 1988001605 A1 WO1988001605 A1 WO 1988001605A1 EP 8700468 W EP8700468 W EP 8700468W WO 8801605 A1 WO8801605 A1 WO 8801605A1
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WO
WIPO (PCT)
Prior art keywords
closure
bottle
opening
contamination
outside
Prior art date
Application number
PCT/EP1987/000468
Other languages
German (de)
French (fr)
Inventor
Johann Hinrich Peters
Original Assignee
C.A. Greiner Und Söhne Gmbh & Co. Kg
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by C.A. Greiner Und Söhne Gmbh & Co. Kg filed Critical C.A. Greiner Und Söhne Gmbh & Co. Kg
Publication of WO1988001605A1 publication Critical patent/WO1988001605A1/en
Priority to GB8903273A priority Critical patent/GB2214498A/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/02—Form or structure of the vessel
    • C12M23/08—Flask, bottle or test tube
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5082—Test tubes per se
    • B01L3/50825—Closing or opening means, corks, bungs
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
    • B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
    • B65D51/00—Closures not otherwise provided for
    • B65D51/16—Closures not otherwise provided for with means for venting air or gas
    • B65D51/1605—Closures not otherwise provided for with means for venting air or gas whereby the interior of the container is maintained in permanent gaseous communication with the exterior
    • B65D51/1616—Closures not otherwise provided for with means for venting air or gas whereby the interior of the container is maintained in permanent gaseous communication with the exterior by means of a filter
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/38—Caps; Covers; Plugs; Pouring means
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M37/00—Means for sterilizing, maintaining sterile conditions or avoiding chemical or biological contamination
    • C12M37/02—Filters

Definitions

  • Contamination-safe closure in particular screw closure for cell culture bottles
  • the invention relates to a contamination-proof closure, in particular screw closure for sterilized cell culture bottles, which are used for the cultivation and maintenance of tissue cultures for biological, virological, immunological and cytological analysis and diagnostics.
  • Such bottles are offered by a wide variety of manufacturers as sterilized, disposable plastic bottles, mostly polystyrene or polycarbonate, PP.
  • the bottles have either a cuboid shape and can be used both horizontally and vertically and are made of crystal-clear plastic for microscopic examinations.
  • such bottles are offered in cylindrical form with a narrow or wide neck or in the form of Erlenmeyer flasks.
  • To close the bottle necks, which are usually equipped with an external thread they are equipped with a screw cap made of plastic, with which the bottles can be hermetically sealed.
  • the bottles are used, for example, for the cultivation and maintenance of cell cultures from cells of freshly trypsinized tissue, permanent and permanent cell cultures of human and animal and vegetable origin, for the biochemical, immunological, cell biological research and diagnostics used.
  • the invention is therefore based on the object with simple means to improve a closure, in particular screw cap or a cell culture bottle of the type mentioned in such a way that sterile ventilation of the bottles is ensured under poor environmental conditions and generally the ventilation of the contamination-proof closure state of the Bottles can be maintained and is guaranteed without deteriorating the handling.
  • This object is achieved according to the invention by the means specified in the main claim or in claim 12.
  • Advantageous Wei developments are specified in the subclaims.
  • the advantages can be seen in the fact that with the cell and microbiological contamination-proof permanent closure of the bottle, a permanent, uniform gas exchange with the surrounding atmosphere is guaranteed, the filter element ensuring that only sterile gas can get into the bottle even in an impure ambient atmosphere. Handling has also become safer, and the filter element also preferably has a place within the closure body that is safe to touch and thus contamination-proof for the user.
  • Bottles used horizontally can also be filled up higher using a shaking mechanism, so that a higher breeding yield can be achieved.
  • FIG. 1 shows a cross section through the closure body with a rectangular bottle
  • Figure 2 shows an enlarged detail cross section of the
  • FIG. 3 shows a perspective view of another commercially available bottle
  • FIG. 4 shows a perspective view of a bottle in the form of an Erlenmeyer flask with a screw cap
  • FIG. 5 shows a modified closure
  • Figure 7 is a bottom view of the innermost part of the
  • Figure 8 is a plan view of the screw closure of Figure
  • Figure 9 shows a detail cross section through another
  • Figure 10 is a plan view of the screw cap of Figure 9 as a cutout.
  • the bottle F is partially filled with a liquid cell culture Z and is closed in a contamination-proof manner by the screw cap 1.
  • the screw cap 1 after Figures 1 and 2 usually have an internal thread 7, which corresponds to the Quss thread of the bottle neck F 'and with its inner shoulder 6 presses tightly onto or against the upper edge of the bottle neck F'.
  • the part 2 of the closure body 1 made of plastic covering the bottle opening F 1 is equipped with at least one or more openings 3.
  • a draining filter support 5 for example in the form of conical support bodies, is integrated on the inside of the closure body 1.
  • a hydrophobic, microporous flat filter cut 4 is attached with its edge in a leak-tight manner, preferably by welding or ultrasound 1 welding.
  • the openings 3 can be covered by a self-adhesive protective film 8, so that the Fi 1 terelemer.t 4 additionally mechanically protected before use or, if necessary, the gas exchange can be allowed or prevented.
  • contamination by touching the flat filter blank 4 and also undesired mechanical damage to the flat filter blank by the user is prevented despite the continuous openings 3.
  • Figures 9 and 10 show an embodiment in which also Damage to the flat filter blank 4 by the user through the openings 3 is practically impossible, since the opening 3 each has an axial and radial offset 3 'within the wall thickness of the plastic body.
  • a silicone stopper 9 is arranged in the screw cap, which is outside the limited filter area, but within the area of the bottle neck opening F ', the Si 1 i konstopfe ⁇ 9 is dimensioned in diameter and thickness so that it is again hermetically automatic seals when the pierced hollow needle is removed again after sampling.
  • the filter element consists of a cartridge-shaped filter body, approximately in the shape of the silicone plug 9.
  • the cover of the screw closure itself is designed in the form of a porous sintered plastic section, which enables gas exchange and prevents liquid leakage .
  • the filter material is also made of a plastic that is inert with respect to the cell cultures, e.g. Polypropylene, PTFE, silicone, hydrophobic cell ul osederivat formed and has a pore size or a cut off, which allows a gas exchange under sterile conditions, is non-toxic or cytotoxic for the liquid and cell cultures and otherwise prevents cell and microorganisms from growing through .
  • a plastic that is inert with respect to the cell cultures, e.g. Polypropylene, PTFE, silicone, hydrophobic cell ul osederivat formed and has a pore size or a cut off, which allows a gas exchange under sterile conditions, is non-toxic or cytotoxic for the liquid and cell cultures and otherwise prevents cell and microorganisms from growing through .

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Clinical Laboratory Science (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Genetics & Genomics (AREA)
  • Sustainable Development (AREA)
  • Molecular Biology (AREA)
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  • Hematology (AREA)
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  • Devices For Use In Laboratory Experiments (AREA)

Abstract

A contamination-proof stopper, in particular a plastic screw cap for sterilised cell culture bottles (F) for cultivating and storing tissue cultures used for biological, virological, immunological and cytological analyses and diagnoses. The part (2) of the plastic stopper (1) that covers the bottle opening (F') incorporates a hydrophobic filtering element (4) made of a filtering material innocuous for the cell cultures (Z) and having a pore size or cut-off that allows a sterile gaseous exchange between the bottle content and the ambient atmosphere to take place and prevents any cellular or microbiological contamination from inside to the outside or vice-versa.

Description

Kontami nati onssicherer Verschluß, insbesondere Schraubverschluß für Zellkulturflaschen Contamination-safe closure, in particular screw closure for cell culture bottles
B E S C H R E I B U N GDESCRIPTION
Die Erfindung betrifft einen kontaminationssicheren Verschluß, insbesondere Schraubverschluß für sterilisierte Zellkulturflaschen, die zur Züchtung und Erhaltung von Gewebekulturen für die biologische, virologi sehe, i munologische und zytologische Analytik und Diagnostik dienen. Derartige Flaschen werden von den verschiedensten Herstellern als sterilisierte Einwegflaschen aus Kunststoff, zumeist Polystyrol oder Polycarbonat, PP, angeboten. Die Flaschen haben dabei entweder quaderförmi ge Gestalt und können sowohl liegend als auch stehend benutzt werden und sind für mikroskoptechnische Untersuchungen aus glasklarem Kunststoff gebildet. In gleicher Weise werden derartige Flaschen in Zylinderform mit engem oder weitem Hals oder in der Form von Erlenmeyer-Kolben angeboten. Zum Verschließen der meist mit Außengewinde ausgestatteten Flaschenhälse sind diese mit einem kappenförmi gen Schraubverschluß aus Kunststoff ausgestattet, mit dem die Flaschen hermetisch dicht verschließbar sind.The invention relates to a contamination-proof closure, in particular screw closure for sterilized cell culture bottles, which are used for the cultivation and maintenance of tissue cultures for biological, virological, immunological and cytological analysis and diagnostics. Such bottles are offered by a wide variety of manufacturers as sterilized, disposable plastic bottles, mostly polystyrene or polycarbonate, PP. The bottles have either a cuboid shape and can be used both horizontally and vertically and are made of crystal-clear plastic for microscopic examinations. In the same way, such bottles are offered in cylindrical form with a narrow or wide neck or in the form of Erlenmeyer flasks. To close the bottle necks, which are usually equipped with an external thread, they are equipped with a screw cap made of plastic, with which the bottles can be hermetically sealed.
Die Flaschen werden z.B. zur Züchtung und Erhaltung von Zellkulturen aus Zellen von frisch trypsini ertem Gewebe, permanenten und se i permanenten Zellkulturen humanen und tierischen und pflanzlichen Ursprungs, für die biochemische, immunologische, zellbiologische Forschung und Diagnostik verwendet.The bottles are used, for example, for the cultivation and maintenance of cell cultures from cells of freshly trypsinized tissue, permanent and permanent cell cultures of human and animal and vegetable origin, for the biochemical, immunological, cell biological research and diagnostics used.
Derartige Flaschen dienen, wie erwähnt, zur Züchtung und Aufbewahrung von Zellkulturen und Mi kroorganis en (Pilze,As mentioned, such bottles are used for the cultivation and storage of cell cultures and microorganisms (fungi,
Bakterien, Hefe, Viren). Diese benötigen jedoch zumeist die Anwesenheit von Gasen (CO , O , p, Hp) bzw. ein Gasaustausch zwischen innen und außen muß möglich sein. Bezüglich der Züchtungstechnik und der sich daraus ergebenden biologischen (Viren, Bakterien, Pilze) Maßnahmen wird auf das Buch von _.H. Peters at al "Monoklonale Antikörper" 1985, verwiesen.Bacteria, yeast, viruses). However, these usually require the presence of gases (CO, O, p, Hp) or a gas exchange between inside and outside must be possible. Regarding breeding technology and the resulting biological (viruses, bacteria, fungi) measures, reference is made to the book by _.H. Peters at al "Monoclonal Antibodies" 1985.
Die bisherige Praxis für die Anwesenheit von bestimmten Gasgemischen bzw. für die Durchführung eines Gasaustausches zwischen dem Fl ascheni nnern und der umgebenden Atmosphäre und umgekehrt erfolgte dadurch, daß der hermetische Flaschenverschluß dadurch beseitigt wurde, daß der Schraubverschluß geringfügig gelöst wurde und der Gasaustausch über die Labyrinthwege der ineinandergreifenden Gewinde von Flaschenhals und Verschluß erfolgte.The previous practice for the presence of certain gas mixtures or for carrying out a gas exchange between the flasscheni men and the surrounding atmosphere and vice versa was that the hermetic bottle cap was removed by slightly loosening the screw cap and gas exchange via the labyrinth paths the interlocking thread of the bottle neck and closure was done.
Eine solche Maßnahme hat mehrere Nachteile, die darin zu sehen sind, daß der Austausch zu langwierig ist, da häufig eine spontane Gaszufuhr bzw. Austausch erwünscht ist. Der Gasaustausch in dieser Form ist nur vertretbar, wenn der Gasaustausch unter Reinraumbedingungen erfolgt, d.h. die umgebende Atmosphäre weitgehend steril und partikelfrei ist. Durch das Lösen des Schraubverschlusses wird die an sich erwünschte hermetische Abdichtung der Flasche aufgehoben. Da der Flascheninhalt häufig trotz eines niedrigen Füllstandes bis in den Bereich der Flaschenöffnung treten kann, z.B. durch eine Schüttelmechanik oder beim Bewegen und Transport, ist nicht auszuschließen, daß bei gelockertem Gewindeverschluß biologisch z.B. virologisch bedenkliche oder toxische Flüssigkeiten sich den Weg durch das Gewinde nach außen suchen und somit die Gefahr besteht, daß Benutzer bei der Handhabung infiziert werden. In gleicher Weise besteht natürlich die Gefahr, daß die Benutzer bei der Handhabung die Zellkulturen von außen her mit Keimen kontaminieren. Desgleichen kann sich der Spalt im Gewinde durch Kondenswasser oder durch das Schütteln mit Flüssigkeit füllen und den Gasaustausch fast vollständig blockieren.Such a measure has several disadvantages, which can be seen in the fact that the exchange is too lengthy, since spontaneous gas supply or exchange is often desired. Gas exchange in this form is only justifiable if the gas exchange takes place under clean room conditions, ie the surrounding atmosphere is largely sterile and particle-free. By loosening the screw cap, the desired hermetic seal of the bottle is released. Since the contents of the bottle can often reach the area of the bottle opening despite a low level, e.g. by means of a shaking mechanism or when moving and transporting, it cannot be ruled out that with a loosened screw cap, biologically virulent or toxic liquids, for example, will find their way out through the thread search and thus there is a risk that users are infected during handling. In the same way, there is of course the risk that the users will contaminate the cell cultures from the outside with germs during handling. Likewise, the gap in the thread can fill with condensation or by shaking with liquid and block the gas exchange almost completely.
Dies gilt insbesondere auch für die in der Praxis immer noch übliche Methode, z.B. Erlenmeyer-Kolben mit einem sterilen Wattestopfen zu verschließen.This applies in particular to the method that is still common in practice, e.g. Seal the Erlenmeyer flask with a sterile cotton plug.
Der Erfindung l iegt daher die Aufgabe zugrunde, mit einfachen Mitteln einen Verschluß, insbesondere Schraubverschluß bzw. eine Zellkulturflasche der eingangs genannten Art so zu verbessern, daß auch eine sterile Belüftung der Flaschen unter schlechten Umgebungsbedingungen gewährleistet ist und generell bei der Belüftung der kontaminationssichere Verschlußzustand der Flaschen beibehalten werden kann und gewährleistet ist, ohne die Handhabung dadurch zu verschlechtern. Diese Aufgabe wird erfindungsgemäß durch die im Hauptanspruch bzw. im Anspruch 12 angegebenen Mittel gelöst. Vorteilhafte Wei erbildungen sind in den Unteransprüchen angegeben.The invention is therefore based on the object with simple means to improve a closure, in particular screw cap or a cell culture bottle of the type mentioned in such a way that sterile ventilation of the bottles is ensured under poor environmental conditions and generally the ventilation of the contamination-proof closure state of the Bottles can be maintained and is guaranteed without deteriorating the handling. This object is achieved according to the invention by the means specified in the main claim or in claim 12. Advantageous Wei developments are specified in the subclaims.
Die Vorteile sind darin zu sehen, daß bei dem zell- und mikrobiologisch kontaminationssicheren permanenten Verschluß der Flasche ein permanenter gleichmäßiger Gasaustausch mit der umgebenden Atmosphäre gewährleistet ist, wobei das Filterelement gewährleistet, daß auch bei unreiner Umgebungsatmosphäre nur steriles Gas in die Flasche gelangen kann. Auch die Handhabung ist sicherer geworden, und auch das Fi1terel ement hat bevorzugt innerhalb des Verschlußkörpers einen für den Benutzer berührungssicheren und damit einen kontaminationssicheren Platz inne.The advantages can be seen in the fact that with the cell and microbiological contamination-proof permanent closure of the bottle, a permanent, uniform gas exchange with the surrounding atmosphere is guaranteed, the filter element ensuring that only sterile gas can get into the bottle even in an impure ambient atmosphere. Handling has also become safer, and the filter element also preferably has a place within the closure body that is safe to touch and thus contamination-proof for the user.
Liegend benutzte Flaschen können auch bei Anwendung einer Schüttelmechanik höher aufgefüllt werden, so daß eine größere Zuchtausbeute erreicht werden kann.Bottles used horizontally can also be filled up higher using a shaking mechanism, so that a higher breeding yield can be achieved.
Der Erfindungsgedanke ist in mehreren Ausführungsbeispielen anhand der beiliegenden Zeichnung näher erläutert. Dabei zeigt:The inventive concept is explained in more detail in several exemplary embodiments with reference to the accompanying drawing. It shows:
Figur 1 einen Querschnitt durch den Verschlußkörper mit einer quaderförmigen Flaschen,FIG. 1 shows a cross section through the closure body with a rectangular bottle,
Figur 2 einen vergrößerten Detailquerschnitt desFigure 2 shows an enlarged detail cross section of the
Flaschenhalses mit abgewandeltem Verschluß, Figur 3 eine perspektivische Ansicht einer anderen handelsüblichen Flasche,Bottle neck with modified closure, FIG. 3 shows a perspective view of another commercially available bottle,
Figur 4 eine perspektivische Ansicht einer Flasche in Form eines Erlenmeyer-Kolben mit Schraubverschluß,FIG. 4 shows a perspective view of a bottle in the form of an Erlenmeyer flask with a screw cap,
Figur 5 einen abgewandelten Verschluß,FIG. 5 shows a modified closure,
Figur 6 den Schraubverschluß in einer weiteren Variante als Schnitt,6 shows the screw cap in a further variant as a section,
Figur 7 eine Untersicht in das Innerste desFigure 7 is a bottom view of the innermost part of the
Schraubverschlusses nach Figur 4 ohne Filterelement.Screw cap according to Figure 4 without filter element.
Figur 8 eine Draufsicht auf den Schraubverschluß nach FigurFigure 8 is a plan view of the screw closure of Figure
6 ohne Schutzfol i e,6 without protective film,
Figur 9 einen Detailquerschnitt durch eine andereFigure 9 shows a detail cross section through another
Ausführungsform eines Schraubverschlusses mit versetzt angeordneten Durchbrechungen undEmbodiment of a screw cap with openings and offset
Figur 10 eine Draufsi cht auf den Schraubverschluß nach Figur 9 als Ausschni tt .Figure 10 is a plan view of the screw cap of Figure 9 as a cutout.
Gemäß Figur 1 ist die Flasche F mit einer flüssigen Zellkultur Z teilweise gefüllt und durch den Schraubverschluß 1 kontaminationssicher verschlossen. Der Schraubverschluß 1 nach Figur 1 und 2 hat üblicherweise ein Innengewinde 7, welches mit dem Qußengewinde des Flaschenhalses F' korrespondiert und sich mit seiner inneren Schulter 6 dicht auf oder an den Oberrand des Flaschenhalses F' anpreßt.According to FIG. 1, the bottle F is partially filled with a liquid cell culture Z and is closed in a contamination-proof manner by the screw cap 1. The screw cap 1 after Figures 1 and 2 usually have an internal thread 7, which corresponds to the Quss thread of the bottle neck F 'and with its inner shoulder 6 presses tightly onto or against the upper edge of the bottle neck F'.
Erfindungsgemäß ist der die Flaschenöffnung F1 abdeckende Teil 2 des Verschlußkörpers 1 aus Kunststoff mit mindestens einer oder mehreren Durchbrechungen 3 ausgestattet. In der Ausführungsform nach Figur 6 ist auf der Innenseite des Verschlußkörpers 1 eine drainierende Fil terabstützung 5, z.B. in Form konischer Stützkörper integriert. Auf einem kreisförmigen Kragen 2' ist ein hydrophober, mikroporöser Flachfilterzuschni t 4 mit seinem Rand leckdicht befestigt, vorzugsweise durch Siegelung oder Ultraschal 1 verschweißung.According to the invention, the part 2 of the closure body 1 made of plastic covering the bottle opening F 1 is equipped with at least one or more openings 3. In the embodiment according to FIG. 6, a draining filter support 5, for example in the form of conical support bodies, is integrated on the inside of the closure body 1. On a circular collar 2 ', a hydrophobic, microporous flat filter cut 4 is attached with its edge in a leak-tight manner, preferably by welding or ultrasound 1 welding.
Gemäß Figur 6, 9 können die Durchbrechungen 3 insgesamt durch eine selbstklebende Schutzfolie 8 abgedeckt sein, so daß das Fi 1 terelemer.t 4 vor Benutzung zusätzlich mechanisch geschützt st bzw. bedarfsweise der Gasaustausch erlaubt oder verhindert werden kann. Bei der Ausfühnngsform des Schraubverschlusses nach Figur 5 bis 10 wird trotz der durchgehenden Durchbrechungen 3 eine Kontamination durch Berührung des Flachfilterzuschnittes 4 und auch eine ungewollte mechanische Beschädigung des Flachfilterzuschnitts durch den Benutzer verhindert.According to Figures 6, 9, the openings 3 can be covered by a self-adhesive protective film 8, so that the Fi 1 terelemer.t 4 additionally mechanically protected before use or, if necessary, the gas exchange can be allowed or prevented. In the embodiment of the screw cap according to FIGS. 5 to 10, contamination by touching the flat filter blank 4 and also undesired mechanical damage to the flat filter blank by the user is prevented despite the continuous openings 3.
Figur 9 und 10 zeigt eine Ausführungsform, bei der auch eine Beschädigung des Flachfilterzuschnittes 4 durch den Benutzer durch die Durchbrechungen 3 hindurch praktisch ausgeschlossen ist, da die Durchbrechung 3 jeweils einen axialen und radialen Versatz 3' innerhalb der Wandstärke des Kunststoffkörpers aufweist.Figures 9 and 10 show an embodiment in which also Damage to the flat filter blank 4 by the user through the openings 3 is practically impossible, since the opening 3 each has an axial and radial offset 3 'within the wall thickness of the plastic body.
Um dem Benutzer unter den vorbeschriebenen biologisch kontaminationssicheren Arbeitsbedingungen auch eine Probeentnahme des Flascheninhaltes zu ermöglichen, ohne den Schraubverschluß ganz zu entfernen, ist gemäß derIn order to enable the user to take a sample of the bottle contents under the previously described, biologically contamination-proof working conditions, without completely removing the screw cap, according to the
Ausführungsform nach Figur 9 und 10 im Schraubverschluß ein Silikonstopfen 9 angeordnet, der außerhalb des eingegrenzten Filterbereiches, jedoch innerhalb des Bereiches der Flaschenhalsöffnung F' liegt, der Si 1 i konstopfeπ 9 ist dabei in Durchmesser und Stärke so bemessen, daß sich dieser wieder hermetisch selbsttätig abdichtet, wenn die eingestochene Hohlnadel nach der Probeentnahme wieder entfernt wird.Embodiment according to Figures 9 and 10, a silicone stopper 9 is arranged in the screw cap, which is outside the limited filter area, but within the area of the bottle neck opening F ', the Si 1 i konstopfeπ 9 is dimensioned in diameter and thickness so that it is again hermetically automatic seals when the pierced hollow needle is removed again after sampling.
In einer nicht dargestellten Ausführungsform besteht das Filterelement aus einem patronenförmi gen Filterkörper, etwa in der Gestalt des Silikonstopfens 9. In einer weiteren nicht dargestellten Ausführungsform ist die Decke des Schraubverschlusses selbst in Form eines porösen gesinterten Kunststoffabschnittes ausgebildet, der einen Gasaustausch ermöglicht und einen Flüssigkeitsaustritt unterbindet.In one embodiment, not shown, the filter element consists of a cartridge-shaped filter body, approximately in the shape of the silicone plug 9. In a further embodiment, not shown, the cover of the screw closure itself is designed in the form of a porous sintered plastic section, which enables gas exchange and prevents liquid leakage .
In der Ausführung nach Figur 3 ist an der Flaschenwand bzw. Flaschenschulter ein Fenster angeordnet, das mit dem Filterelement 4 und Schutzfolie 8 verschlossen ist. Der Schraubverschluß ist dabei ohne Filterelement ausgebildet.In the embodiment according to FIG. 3, on the bottle wall or Bottle shoulder arranged a window, which is closed with the filter element 4 and protective film 8. The screw cap is designed without a filter element.
In allen Fällen ist auch das Filtermaterial aus einem bezüglich der Zellkulturen inerten Kunststoff, z.B. Polypropylen, PTFE, Silikon, hydrophobem Zeil ul osederivat gebildet und hat eine Porengröße bzw. ein cut off, die einersetis einen Gasaustausch unter Sterilbedingungen zuläßt, nicht toxisch oder zytotoxi sehen für die Flüssigkeit und Zellkulturen ist und anderersetis auch ein Durchwachsen von Zellen und Mikroorganismen verhindert. In all cases, the filter material is also made of a plastic that is inert with respect to the cell cultures, e.g. Polypropylene, PTFE, silicone, hydrophobic cell ul osederivat formed and has a pore size or a cut off, which allows a gas exchange under sterile conditions, is non-toxic or cytotoxic for the liquid and cell cultures and otherwise prevents cell and microorganisms from growing through .

Claims

A N S P R Ü C H EEXPECTATIONS
Kontaminationssicherer Verschluß, insbesondere Schraubverschluß aus Kunststoff für sterilisierte Zellkulturflaschen, die zur Züchtung und Erhaltung von Zeil- und Gewebekulturen und für die biologische, vi rol ogi sehe, immunologische und cytologische Analytik und Diagnostik dienen, dadurch gekennzeichnet, daß der die Flaschenöffnung (F1 ) abdeckende Teil Contamination-proof closure, in particular screw cap made of plastic for sterilized cell culture bottles, which are used for the cultivation and maintenance of cell and tissue cultures and for biological, viral, immunological and cytological analysis and diagnostics, characterized in that the bottle opening (F 1 ) covering part
(2) des Verschlußkörpers (1) aus Kunststoff ein damit integriertes hydrophobes Filterelement (4) aufweist, das aus einem für die Zellkulturen (Z) inerten Filtermaterial gebildet ist und eine den sterilen Gasaustausch zwischen dem Flascheninhalt und der Umgebungsatmosphäre erlaubende und eine zelluläre und mikrobiologische Kontamination von innen nach außen und umgekehrt verhindernde Porengröße bzw. cut off aufweist.(2) of the closure body (1) made of plastic has a hydrophobic filter element (4) integrated therewith, which is formed from a filter material that is inert to the cell cultures (Z) and which allows sterile gas exchange between the bottle contents and the ambient atmosphere and is cellular and microbiological Contamination from the inside to the outside and vice versa has a preventing pore size or cut off.
Verschluß nach Anspruch 1 , dadurch gekennzeichnet, daß das Filterelement (4) berührungssicher von außen hinter mindestens einer Durchbrechung Closure according to claim 1, characterized in that the filter element (4) is safe to touch from the outside behind at least one opening
(3) des die Flaschenöffnung (F1 ) abdeckenden Teiles (2) des Verschlußkörpers (1 ) liegt.(3) of the part (2) of the closure body (1) covering the bottle opening (F 1 ).
Verschluß nach Anspruch 1 und 2, dadurch gekennzeichnet, daß das Filterelement durch einen gesinterten porösen Abschnitt des Verschlußkörpers (1) aus Kunststoff gebildet i st. Closure according to claims 1 and 2, characterized in that the filter element is formed by a sintered porous section of the closure body (1) made of plastic.
4. Verschluß nach Anspruch 1 und 2, dadurch gekennzeichnet, daß das Filterelement aus einem im Verschlußkörper (1 ) eingebetteten Patronenfil er gebildet ist.4. Closure according to claim 1 and 2, characterized in that the filter element is formed from a cartridge filter embedded in the closure body (1).
5. Verschluß nach Ansprich 1 und 2, dadurch gekennzeichnet, daß das Filterelement (4) aus einem mikroporösen Flachfilterzuschnitt gebildet ist, der auf der Innenseite bzw. Außenseite des mit mindestens einer Durchbrechung (3), vorzugsweise mehreren Durchbrechungen (3) versehenen Verschlußkörpers (1) im Bereich der abzudeckenden Flaschenöffnung (F1) aufgesiegelt, aufgeschweißt oder aufgeklebt ist.5. Closure according to claims 1 and 2, characterized in that the filter element (4) is formed from a microporous flat filter blank which is provided on the inside or outside of the closure body (3) which is provided with at least one opening (3), preferably several openings (3). 1) is sealed, welded or glued on in the area of the bottle opening (F 1 ) to be covered.
6. Verschluß nach Anspruch 1 und 5, dadurch gekennzeichnet, daß der vom festgelegten Rand (21) des6. Closure according to claim 1 and 5, characterized in that the defined edge (2 1 ) of the
Flachfilterzuschnittes (4) eingegrenzte innere Bereich des Verschlußkörpers (1) eine drainierende Fi 1 terabstützung (5) aufweist.The inner region of the closure body (1) delimited by the flat filter blank (4) has a draining filter support (5).
7. Verschluß nach Anspruch 1 , 5 und 6, dadurch gekennzeichnet, daß im Verschlußkörper (1) innerhalb der Wandungsdicke die Durchbrechungen (3) einen den direkten axialen Durchlaß verdeckenden axialen und radialen Querschnittsversatz (3') aufweisen, der die mikroporöse Membran (4) gegen Berührung von außen und gegen mechanische Beschädigung von außen schützt. 7. Closure according to claim 1, 5 and 6, characterized in that in the closure body (1) within the wall thickness, the openings (3) have an axial and radial cross-sectional offset (3 ') which covers the direct axial passage and which covers the microporous membrane (4 ) protects against contact from outside and against mechanical damage from outside.
8. Verschluß nach Anspruch 1 bis 7, dadurch gekennzeichnet, daß die Oberseite des die Flaschenöffnung (F1) abdeckenden und die Durchbrechungen aufweisende Bereich des Verschlußkörpers (1) eben ausgebildet ist und eine die Durchbrechungen (3) abdeckende und verschließende, entfernbare Schutzfolie (8) aufweist.8. Closure according to claims 1 to 7, characterized in that the top of the area of the closure body (1) covering the bottle opening (F 1 ) and having the openings is flat and a removable protective film (3) covering and closing the openings (3). 8).
9. Verschluß nach Anspruch 1 bis 7, dadurch gekennzeichnet, daß die mikroporöse Membran eine Porengröße zwischen 10 um und 0,0001 um aufweist.9. Closure according to claims 1 to 7, characterized in that the microporous membrane has a pore size between 10 μm and 0.0001 μm.
10. Verschluß nach Anspruch 1 bis 9, dadurch gekennzeichnet, daß außerhalb des von dem Filterelement (4) eingegrenzten Bereiches des Verschlußkörpers (1) und innerhalb des von der Flaschenöffnung (F1) eingegrenzten Bereiches im Verschlußkörper (1) in einem Abschnitt seiner Wandung (2) ein zur Probeentnahme mittels Nadel geeigneter Verschlußstopfen 89) aus Silikon oder dergleichen angeordnet ist, dessen Querschnitt so bemessen ist, daß sich die Öffnung für die Nadel selbsttätig wieder schließt.10. Closure according to claims 1 to 9, characterized in that outside the area of the closure body (1) delimited by the filter element (4) and within the area delimited by the bottle opening (F 1 ) in the closure body (1) in a section of its wall (2) a sealing plug 89) made of silicone or the like suitable for taking samples using a needle is arranged, the cross section of which is dimensioned such that the opening for the needle automatically closes again.
11. Kontaminationssicherer Verschluß mit sterilisierter11. Contamination-proof closure with sterilized
Zel 1kul turfl asche, gekennzeichnet nach einem der Ansprüche 1 bis 10.Zel 1kul turf ash, characterized according to one of claims 1 to 10.
12. Kontaminationssicherer Verschluß mit Zel 1 kul turfl asche aus Kunststoff zur Züchtung und Erhaltung von Gewebekulturen und für die biologische, vi rologi sehe, immunologische und cytologische Analytik und Diagnostik, dadurch gekennzeichnet, daß die Zeil kulturfl asche (F) unterhalb des Schraubverschlusses (1 ) im Bereich des Flaschenhalses bzw. Flaschenschulter eine Durchbrechung aufweist, die von einem randseitig mit der Durchbrechung dichtend verbunden hydrophoben Filterelement (4) verschlossen ist, das aus einem für die Zellkulturen (Z) inerten Filtermaterial gebildet ist und eine den sterilen Gasaustausch zwischen dem Fl ascheni nhal t und der Umgebungsatmosphäre erlaubende und eine zelluläre und mikrobiologische Kontamination von innen nach außen und umgekehrt verhindernde Porengröße bzw. cut off aufweist. 12. Contamination-proof closure with Zel 1 culture bottle made of plastic for growing and maintaining tissue cultures and for biological, viral, immunological and cytological analysis and diagnostics, characterized in that the cell culture bottle (F) has an opening below the screw cap (1) in the area of the bottle neck or bottle shoulder, which has an opening on the edge with the The opening is sealed with a hydrophobic filter element (4), which is formed from a filter material that is inert to the cell cultures (Z) and allows sterile gas exchange between the bottle contents and the ambient atmosphere and prevents cellular and microbiological contamination from the inside to the outside Conversely, preventing pore size or cut off.
PCT/EP1987/000468 1986-08-26 1987-08-20 Contamination-proof stopper, in particular screw cap, for cell culture bottles WO1988001605A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
GB8903273A GB2214498A (en) 1986-08-26 1989-02-14 Contamination-proof stopper,in particular screw cap,for cell culture bottles

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DEP3628930.2 1986-08-26
DE19863628930 DE3628930A1 (en) 1986-08-26 1986-08-26 CONTAMINATION-SAFE CAP, IN PARTICULAR SCREW CAP FOR CELL CULTURE BOTTLES

Publications (1)

Publication Number Publication Date
WO1988001605A1 true WO1988001605A1 (en) 1988-03-10

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Application Number Title Priority Date Filing Date
PCT/EP1987/000468 WO1988001605A1 (en) 1986-08-26 1987-08-20 Contamination-proof stopper, in particular screw cap, for cell culture bottles

Country Status (5)

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JP (1) JPH01503595A (en)
DE (1) DE3628930A1 (en)
FR (1) FR2603258B3 (en)
GB (1) GB2214498A (en)
WO (1) WO1988001605A1 (en)

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WO1989006272A3 (en) * 1987-12-30 1989-08-24 American Sterilizer Co Sterilizable gas permeable container for use in culturing living cells
EP0337677A2 (en) * 1988-04-11 1989-10-18 Costar Corporation Vent cap
EP0593840A1 (en) * 1992-10-23 1994-04-27 The Procter & Gamble Company Process for making thermoplastic materials comprising a network of microchannels
FR2698375A1 (en) * 1992-11-20 1994-05-27 Biopredic Sarl Container for transporting and storing liquids used in kits for in vitro tests - comprises series of holders with caps which have central outlets and sealing layers.
FR2699894A1 (en) * 1992-12-29 1994-07-01 De Buyer Herve Insulated container for liquid and solid food products
EP0641856A2 (en) * 1993-09-01 1995-03-08 Becton, Dickinson and Company Vessel and closure assembly
WO1996006018A1 (en) * 1994-08-19 1996-02-29 W. L. Gore & Associates, Inc. Vented vial for freeze-drying and method of minimizing contamination of freeze-dried products
EP0734769A1 (en) * 1995-03-31 1996-10-02 Roche Diagnostics GmbH Lid for closing containers
EP0791649A3 (en) * 1996-02-26 1998-05-20 Arbor Technologies, Inc. Flask vent and method of making same
US5801054A (en) * 1996-09-19 1998-09-01 The United States Of America As Represented By The Secretary Of The Air Force Cell culture vessel with self-maintained atmosphere
GB2327372A (en) * 1997-07-19 1999-01-27 Gore & Ass Sterilisable vent
US6095356A (en) * 1999-03-10 2000-08-01 Children's Medical Center Corp. Vented flask cap for absorbing radioactive gases
US6193088B1 (en) * 1996-02-26 2001-02-27 Monty E. Vincent Flask vent and method of making same
EP2085464A1 (en) 2008-02-01 2009-08-05 Eppendorf AG Laboratory vessel with shiftable vessel closure
WO2009128892A2 (en) * 2008-04-18 2009-10-22 Corning Incorporated Flexible membrane valve for cell culture vessel
FR2948646A1 (en) * 2009-07-29 2011-02-04 Pascal Boudjema Storage device for follicular units used to treat baldness, has transfer unit transferring biological units one by one towards storage reservoir in operation state, where reservoir is conformed for storing biological units behind each other
WO2012156682A1 (en) * 2011-05-16 2012-11-22 Parker Hannifin Manufacturing Limited Bioreactor chamber
WO2012156683A1 (en) * 2011-05-16 2012-11-22 Parker Hannifin Manufacturing Limited Bioreactor chamber
EP3034616A1 (en) * 2014-12-17 2016-06-22 Mohammad Salehi Device for producing and/or cleaning nanoparticle coupled biomaterials and method using the same
CN105691878A (en) * 2016-04-14 2016-06-22 李悦晨 Beverage container and sealing cap thereof
US20210087508A1 (en) * 2019-09-20 2021-03-25 Scientific Industries, Inc. Cell culture flasks, sensor inserts, and systems and methods comprising the same

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Cited By (30)

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Publication number Priority date Publication date Assignee Title
US4935371A (en) * 1986-12-31 1990-06-19 American Sterilizer Company Sterilizable gas permeable container for use in culturing living cells
WO1989006272A3 (en) * 1987-12-30 1989-08-24 American Sterilizer Co Sterilizable gas permeable container for use in culturing living cells
EP0337677A2 (en) * 1988-04-11 1989-10-18 Costar Corporation Vent cap
EP0337677A3 (en) * 1988-04-11 1990-04-04 Costar Corporation Vent cap
EP0593840A1 (en) * 1992-10-23 1994-04-27 The Procter & Gamble Company Process for making thermoplastic materials comprising a network of microchannels
FR2698375A1 (en) * 1992-11-20 1994-05-27 Biopredic Sarl Container for transporting and storing liquids used in kits for in vitro tests - comprises series of holders with caps which have central outlets and sealing layers.
FR2699894A1 (en) * 1992-12-29 1994-07-01 De Buyer Herve Insulated container for liquid and solid food products
EP0641856A3 (en) * 1993-09-01 1998-01-07 Becton, Dickinson and Company Vessel and closure assembly
EP0641856A2 (en) * 1993-09-01 1995-03-08 Becton, Dickinson and Company Vessel and closure assembly
WO1996006018A1 (en) * 1994-08-19 1996-02-29 W. L. Gore & Associates, Inc. Vented vial for freeze-drying and method of minimizing contamination of freeze-dried products
US5522155A (en) * 1994-08-19 1996-06-04 W. L. Gore & Associates, Inc. Vented vial method of minimizing contamination of freeze-dried products
US5732837A (en) * 1994-08-19 1998-03-31 W. L. Gore & Associates, Inc. Vented vial closure member for freeze-drying which minimizes contamination of freeze-dried products
EP0734769A1 (en) * 1995-03-31 1996-10-02 Roche Diagnostics GmbH Lid for closing containers
EP0791649A3 (en) * 1996-02-26 1998-05-20 Arbor Technologies, Inc. Flask vent and method of making same
US6170684B1 (en) 1996-02-26 2001-01-09 Monty E. Vincent Flask vent and method of making same
US6193088B1 (en) * 1996-02-26 2001-02-27 Monty E. Vincent Flask vent and method of making same
US5801054A (en) * 1996-09-19 1998-09-01 The United States Of America As Represented By The Secretary Of The Air Force Cell culture vessel with self-maintained atmosphere
GB2327372A (en) * 1997-07-19 1999-01-27 Gore & Ass Sterilisable vent
US6095356A (en) * 1999-03-10 2000-08-01 Children's Medical Center Corp. Vented flask cap for absorbing radioactive gases
EP2085464A1 (en) 2008-02-01 2009-08-05 Eppendorf AG Laboratory vessel with shiftable vessel closure
US8177082B2 (en) 2008-04-18 2012-05-15 Corning Incorporated Flexible membrane valve for cell culture vessel
WO2009128892A3 (en) * 2008-04-18 2011-12-29 Corning Incorporated Flexible membrane valve for cell culture vessel
WO2009128892A2 (en) * 2008-04-18 2009-10-22 Corning Incorporated Flexible membrane valve for cell culture vessel
FR2948646A1 (en) * 2009-07-29 2011-02-04 Pascal Boudjema Storage device for follicular units used to treat baldness, has transfer unit transferring biological units one by one towards storage reservoir in operation state, where reservoir is conformed for storing biological units behind each other
WO2012156682A1 (en) * 2011-05-16 2012-11-22 Parker Hannifin Manufacturing Limited Bioreactor chamber
WO2012156683A1 (en) * 2011-05-16 2012-11-22 Parker Hannifin Manufacturing Limited Bioreactor chamber
US9422516B2 (en) 2011-05-16 2016-08-23 Parker-Hannifin Manufacturing Limited Bioreactor chamber
EP3034616A1 (en) * 2014-12-17 2016-06-22 Mohammad Salehi Device for producing and/or cleaning nanoparticle coupled biomaterials and method using the same
CN105691878A (en) * 2016-04-14 2016-06-22 李悦晨 Beverage container and sealing cap thereof
US20210087508A1 (en) * 2019-09-20 2021-03-25 Scientific Industries, Inc. Cell culture flasks, sensor inserts, and systems and methods comprising the same

Also Published As

Publication number Publication date
GB8903273D0 (en) 1989-05-17
GB2214498A (en) 1989-09-06
JPH01503595A (en) 1989-12-07
DE3628930A1 (en) 1988-05-05
FR2603258B3 (en) 1988-11-25
FR2603258A1 (en) 1988-03-04

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