WO2014016607A1 - Dispositif de culture cellulaire autoclavable - Google Patents

Dispositif de culture cellulaire autoclavable Download PDF

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Publication number
WO2014016607A1
WO2014016607A1 PCT/GB2013/052000 GB2013052000W WO2014016607A1 WO 2014016607 A1 WO2014016607 A1 WO 2014016607A1 GB 2013052000 W GB2013052000 W GB 2013052000W WO 2014016607 A1 WO2014016607 A1 WO 2014016607A1
Authority
WO
WIPO (PCT)
Prior art keywords
lid
base
side wall
stacked configuration
lids
Prior art date
Application number
PCT/GB2013/052000
Other languages
English (en)
Inventor
David LYDALL
Original Assignee
University Of Newcastle Upon Tyne
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 University Of Newcastle Upon Tyne filed Critical University Of Newcastle Upon Tyne
Publication of WO2014016607A1 publication Critical patent/WO2014016607A1/fr

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Classifications

    • 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
    • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • B01L3/50853—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates with covers or lids
    • 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
    • C12M23/04—Flat or tray type, drawers
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/0005—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
    • A61L2/0011—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using physical methods
    • A61L2/0023—Heat
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/02—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using physical phenomena
    • A61L2/04—Heat
    • A61L2/06—Hot gas
    • A61L2/07—Steam
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/025—Align devices or objects to ensure defined positions relative to each other
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0829—Multi-well plates; Microtitration plates

Definitions

  • This invention relates to a device for culturing at least one cell, the device comprising a lid and a base, wherein at least one of the lid and/or base consists of (i) an autoclavable material and (ii) is configured to be autoclavable in a stacked configuration.
  • the invention also provides a lid with the equivalent properties and advantages.
  • Typical apparatus used for such research includes microtitre plates (e.g. 96 well plates), Petri-dishes or tissue culture flasks.
  • Such conventional apparatus typically includes a base container into which a cell sample is deposited and some form of lid or seal to prevent or minimize, inter alia, loss of liquid from the sample through evaporation, sample degradation, and/or contamination from external sources.
  • the base container and lid or seal are
  • the present invention provides an improved device for culturing at least one cell that overcomes a number of the disadvantages of the prior art.
  • the invention relates to a modified device for culturing at least one cell.
  • the device is designed such that it is suitable for re-use and can be stored and/or autoclaved in a number of different stacked configurations.
  • the invention provides a device for culturing at least one cell comprising: (a) a base having an upper surface and a lower surface, the upper surface having at least one base side wall projecting therefrom, wherein the upper surface of the base and the at least one base side wall define at least one sample receiving area; and (b) a lid having an upper face and a lower face, the lower face having at least one lid side wall projecting therefrom, the lid side wall being for mounting against the base side wall to enclose the at least one sample receiving area; wherein the base and/or lid (i) consists of an autoclavable material; and (ii) is configured to be autoclavable in a stacked configuration.
  • the lid consists of an autoclavable material.
  • the base consists of an autoclavable material.
  • the at least one base side wall projects orthogonally out from the upper surface of the base.
  • the at least one lid side wall projects orthogonally out from the lower face of the lid.
  • the autoclavable material is selected from the group consisting of polycarbonate, polyurethane, polypropylene, high temperature SAN, high temperature grade ABS, polymethylpentene and mixtures thereof.
  • the lid and base consist of an autoclavable material and the lid is configured for autoclaving when the lid side wall is mounted against the base side wall in a stacked configuration.
  • the lower face of the lid is configured to enable air flow between the lid and the base when the lid side wall is mounted against the base side wall in a stacked configuration.
  • the lower face of the lid includes a plurality of spacing elements to spatially separate the lower face of the lid from the base side wall when the lid side wall is mounted against the base side wall in a stacked configuration.
  • the lid consists of an autoclavable material and is configured for autoclaving in a stacked configuration with one or more identical lids.
  • the upper face of the lid is configured to enable air flow between the lid and one or more identical lids when a plurality of identical lids is placed in a stacked configuration.
  • the upper face of the lid includes a plurality of spacing elements to spatially separate the upper face of the lid from a lid side wall of an adjacent identical lid when a plurality of identical lids is placed in a stacked configuration.
  • the upper face of the lid further comprises a plurality of ridges configured to prevent or minimise lateral movement of an adjacent identical lid relative to the lid when a plurality of identical lids is placed in a stacked configuration.
  • the base consists of an autoclavable material and is configured for autoclaving in a stacked configuration with one or more identical bases.
  • the lower surface of the base is configured to enable air flow between the base and one or more identical bases when a plurality of identical bases is placed in a stacked configuration.
  • the lower surface of the base includes a plurality of spacing elements to spatially separate the lower surface of the base from a base side wall of an adjacent identical base when a plurality of identical bases is placed in a stacked configuration.
  • the base further comprises an outer ridge on the lower surface of the base configured to prevent or minimise lateral movement of an adjacent identical base relative to the base when a plurality of identical bases are placed in a stacked configuration.
  • the lid and the base consist of an autoclavable material and the lid is configured such that the device is for autoclaving in a stacked configuration with one or more identical devices.
  • the upper face of the lid is configured to enable air flow between the device and one or more identical devices when a plurality of identical devices is placed in a stacked configuration.
  • the upper face of the lid includes a plurality of spacing elements to spatially separate the upper face of the lid from a lower surface of a base in an adjacent identical device when a plurality of identical devices is placed in a stacked configuration.
  • the upper face of the lid further comprises a plurality of ridges configured to prevent or minimise lateral movement of an adjacent identical device relative to the device when a plurality of identical devices is placed in a stacked configuration.
  • the lid and the base each comprise at least one orientation indicator for indicating a specified orientation of the lid relative to the base. More preferably, the lid and base each comprise two orientation indicators.
  • the orientation indicator comprises a chamfered corner.
  • the device of the invention is substantially circular, substantially square or substantially rectangular in shape.
  • the base comprises one sample receiving area.
  • the base comprises a plurality of sample receiving areas.
  • the base comprises 6, 12, 24, 48, or 96 sample receiving areas.
  • the base side wall consists of a single wall layer.
  • the invention provides a lid for a device for culturing at least one cell, the lid comprising an upper and a lower face, the lower face having at least one lid side wall projecting therefrom, the lid side wall being for mounting against a base side wall of a base to enclose at least one sample receiving area, the base having an upper surface and a lower surface, the upper surface of the base having at least one base side wall projecting therefrom, the upper surface of the base and the at least one base side wall defining the at least one sample receiving area, wherein the lid consists of an autoclavable material and is configured for autoclaving in a stacked configuration.
  • the at least one lid side wall projects orthogonally out from the lower face of the lid.
  • the autoclavable material is selected from the group consisting of polycarbonate, polyurethane, polypropylene, high temperature SAN, high temperature grade ABS, polymethylpentene and mixtures thereof.
  • the lid is configured for autoclaving when the lid side wall is mounted against a base side wall of a base in a stacked configuration.
  • the lower face of the lid is configured to enable air flow between the lid and a base when the lid side wall is mounted against a base side wall of a base in a stacked configuration.
  • the lower face of the lid is configured to include a plurality of spacing elements to spatially separate the lower face of the lid from a base side wall of a base when the lid side wall is mounted against a base side wall of a base in a stacked configuration.
  • the lid is configured for autoclaving in a stacked configuration with one or more identical lids.
  • the upper face of the lid is configured to enable air flow between the lid and one or more identical lids when a plurality of identical lids is placed in a stacked configuration.
  • the upper face of the lid includes a plurality of spacing elements to spatially separate the upper face of the lid from a lid side wall of an adjacent identical lid when a plurality of identical lids is placed in a stacked configuration.
  • the upper face of the lid further comprises a plurality of ridges configured to prevent or minimise lateral movement of an adjacent identical lid relative to the lid when a plurality of identical lids is placed in a stacked configuration.
  • the lid is configured such that the lid is for autoclaving as part of a device further comprising a base, the base having an upper surface and a lower surface, the upper surface of the base having at least one base side wall projecting therefrom, the upper surface of the base and the at least one base side wall defining the at least one sample receiving area, the lid side wall being for mounting against the base side wall, wherein the device is in a stacked configuration with one or more identical devices.
  • the upper face of the lid is configured to enable air flow between the device and one or more identical devices when a plurality of identical devices is placed in a stacked configuration.
  • the upper face of the lid includes a plurality of spacing elements to spatially separate the upper face of the lid from a lower surface of a base in an adjacent identical device when a plurality of identical devices is placed in a stacked configuration. Also preferably, the upper face of the lid further comprises a plurality of ridges configured to prevent or minimise lateral movement of an adjacent identical device relative to the device when a plurality of identical devices is placed in a stacked configuration.
  • the lid comprises at least one orientation indicator. More preferably, the lid comprises two orientation indicators.
  • the orientation indicator comprises a chamfered corner.
  • the lid is substantially circular, substantially square or substantially rectangular in shape.
  • the invention provides a device substantially as described herein with reference to the accompanying drawings.
  • the invention provides a lid substantially as described herein with reference to the accompanying drawings.
  • the invention provides a method of generating a stacked
  • the invention provides a method of generating a stacked
  • the invention provides a method of generating a stacked
  • the invention provides a method of autoclaving a plurality of lids, and/or bases as described herein with reference to the accompanying drawings.
  • Figure 1A shows a plan view of an upper surface of a base.
  • Figure 1 B shows a side view of the base shown in Figure 1A.
  • Figure 1 C shows a plan view of a lower surface of a base.
  • Figure 2A shows a plan view of an upper face of a lid.
  • Figure 2B shows a side view of the lid shown in Figure 2A.
  • Figure 3A shows a plan view of a lower face of a lid.
  • Figure 3B shows a side view of the lid shown in Figure 3A.
  • Figure 4 shows a set of drawings of the lid.
  • Figure 5 shows a set of drawings of the base.
  • Figure 6 shows two devices in a stacked configuration.
  • a device for culturing at least one cell may be composed of an autoclavable material that is sufficiently resilient to undergo repeated washing and autoclaving.
  • the inventors also provide a new mechanism for enabling the lids and/or bases of the device to be autoclaved in a stacked configuration.
  • the term “device” refers to a combination of a base and a lid.
  • the base and the lid may be provided in a stacked configuration (e.g. with the lid mounted against the base or the base mounted against the lid) or they may be provided independently.
  • the terms “device”, “vessel” and “apparatus” are used interchangeably herein.
  • the inventors have developed a modified device which advantageously enables any of (i) a plurality of bases, (ii) a plurality of lids, (iii) a plurality of devices, and/or (iv) a lid and a base to be autoclaved in a stacked configuration.
  • stacked configuration refers to a plurality of individual parts (e.g. a plurality of bases, a plurality of lids, a plurality of devices or a lid and a base) that are stacked together in a stable configuration.
  • two or more bases form a stacked configuration when the two or more bases are placed one on top of the other (i.e. layered) in a stable manner such that the bases are more likely to remain stacked than they are likely to topple over.
  • two or more lids form a stacked configuration when the two or more lids are placed one on top of the other (i.e. layered) in a stable manner such that the lids are more likely to remain stacked than they are likely to topple over.
  • two or more devices form a stacked configuration when the two or more devices are placed one on top of the other (i.e. layered) in a stable manner such that the devices are more likely to remain stacked than they are likely to topple over.
  • a lid and a base form a stacked configuration when the lid and the base are placed one on top of the other (i.e. layered; e.g. the lid is mounted against the base or the base is mounted against the lid) in a stable manner such that the lid and base are more likely to remain stacked than they are likely to topple over.
  • the phrases “mounted against” and “for mounting against” refer to the relationship between the base and the lid when the base and the lid are in a stacked configuration (i.e. when the lid is placed against the base). These phrases are intended to encompass temporary (i.e. removable) placement of the lid against the base and permanent (i.e. non-removable) placement of the lid against the base. Further detail relating to the relationship between a base and a lid is provided below.
  • a stacked configuration may be useful during storage, use (e.g. for stacking devices in a cell culture incubator) or autoclaving of the stacked items (e.g. a plurality of bases, a plurality of lids, a plurality of devices or a lid and a base).
  • autoclave refers to a device that is used to sterilize apparatus and supplies using high pressure saturated steam.
  • Autoclaving refers to the process carried out by an autoclave. Typically, apparatus and supplies are subjected to high pressure saturated steam at about 121 °C for approximately 12 to 20 minutes depending on the specific apparatus and supplies being autoclaved (and the size of the load). Autoclaving is a standard technique that is well known to the skilled worker.
  • autoclaving may comprise subjecting the desired apparatus and/or supplies to about 121 °C (e.g. 120°C, 121 °C, or 122 °C) for at least 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19 or 20 minutes or more.
  • 121 °C e.g. 120°C, 121 °C, or 122 °C
  • a base, a lid, or a device is "autoclavable” if it does not significantly warp, deform or discolour when subjected to autoclaving.
  • an autoclavable base, lid, or device displays only insignificant warping, deformation or discoloration when subjected to autoclaving, most preferably displaying no visible warping, deformation or discolouration.
  • a base, a lid, or a device in accordance with the invention is "autoclavable" for repeated cycles of: autoclaving, drying, washing (e.g. in a dish washer), then drying.
  • a base, a lid or a device of the invention can preferably withstand (without significant warping, deformation, or discolouration) multiple rounds of autoclaving, drying, washing (e.g. in a dish washer), then drying.
  • a base, a lid or a device of the invention can withstand at least 5 repeated cycles of autoclaving, drying, washing (e.g. in a dish washer), then drying.
  • a base, a lid or a device of the invention can withstand 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, or more repeated cycles of: autoclaving, drying, washing (e.g. in a dish washer), then drying.
  • the lid, base and/or device of the invention is configured to enable air flow between adjacent components (e.g. two or more lids; two or more bases; a lid and a base; or two or more devices) when they are in a stacked configuration.
  • air flow also encompasses the flow of steam (i.e. the vapor phase of water), for example, during the autoclaving process.
  • steam reaches most, or all of the internal and external (surfaces of the lid, base, and/or device.
  • the configuration of the lid, base and/or device of the invention therefore preferably enables steam penetration of all areas and (surfaces in a stacked
  • a base, a lid, or a device of the invention is composed of (i.e. consists of) an autoclavable material, and hence is autoclavable per se.
  • the autoclavable material is compatible with culturing at least one cell.
  • the autoclavable material is of medical grade.
  • Examples of autoclavable materials that are suitable for the invention include, but are not limited to the following polymers and their derivatives: Polysulfone (e.g. Udel®), Polymethylpentene, PTFE resin, polymethyl methacrylate, polyurethane, polypropylene, high temperature SAN (styrene acrylonitrile copolymerised with e.g.
  • alpha methylstyrene or N phenylmaleinide e.g. Luran®, HH-120 (BASF)
  • styrene maelic anhydride e.g. XIRAN®
  • high temperature grade ABS cycloolefin
  • Trivex® a quasi-thermoset thermoplastic from PPG Industries
  • ZEONEX ® /ZEONOR ® a type of cyclolefin
  • TPX® Polymethylpentene or mixtures thereof.
  • Each material may have different tolerances to autoclaving and/or washing (e.g. using a dishwasher with or without detergent). Optimisation of the autoclaving and washing procedures falls within routine experimentation of a skilled worker.
  • the autoclavable material is selected from the group consisting of polycarbonate, polyurethane, polypropylene, high temperature SAN, high temperature ABS, polymethylpentene or mixtures thereof.
  • the autoclavable material comprises polycarbonate.
  • the autoclavable material consists of polycarbonate (e.g. makrolon®; other brands also exist and are known to the skilled worker).
  • the polycarbonate is of medical grade.
  • the autoclavable material is a mouldable material, preferably a mouldable plastic that, once moulded, tolerates standard autoclave conditions.
  • the material tolerates about 121 °C for about 15 minutes, about 121 °C for about 20 minutes or about 121 °C for about 30 minutes.
  • the lid, base and/or device of the invention is composed of an optically transparent material.
  • Optically transparent materials are suitable for use with conventional optical detection equipment, and therefore may be useful for assays that operate via transmitted light (e.g. absorption, nephelometric and chromogenic spectrophotometric assays etc).
  • the lid, base and/or device may be entirely transparent or portions may be translucent or opaque.
  • the lid, base and/or device of the invention is composed of a translucent or an opaque (e.g. black or white) material.
  • the optical properties of each material provide distinct advantages, for example visualisation of different wavelength emissions, facilitating distinction between white or blue colonies on agar located in the sample receiving area of the base, or measuring fluorescent signals emanating from a cell or organism growing in the sample receiving area of the base.
  • a lid, a base and/or a device in accordance with the invention may be manufactured by various moulding processes known in the art, such as, but not limited to, injection moulding processes.
  • a lid, base and/or device in accordance with the invention can be used with (i.e. is compatible with) all commonly used robots.
  • robots that use standard sized lids/bases/devices for example the S&P Robotics, Beckman, Tecan, Eppendorf, and Caliper Robots
  • robots that use lids/bases/devices with dimensions unique to the robot for example the Singer Robot, which uses the PlusPlate®.
  • Recommended microplate dimensions also known as SBS dimensions
  • the lid, base and/or device of the invention comply with the recommended standard microplate dimensions (also known as SBS dimensions) specified by the Society for Laboratory Automation and Screening.
  • SBS dimensions also known as SBS dimensions
  • the invention provides a base having an upper surface and a lower surface, the upper surface having at least one base side wall projecting therefrom, wherein the upper surface of the base and the at least one base side wall define at least one sample receiving area.
  • the upper surface and lower surface of the base form the two opposing surfaces of a substantially flat bottom of the base.
  • the bottom of the base i.e. the upper surface and the lower surface in combination, and anything in between
  • Factors influencing the strength of the bottom of the base include the material used and the thickness used. Those of ordinary skill in the art will recognise how to select suitable materials and/or thicknesses to provide the desired strength and rigidity.
  • the base may be configured in a wide range of shapes and sizes.
  • the base may be, but is not limited to being, substantially (i.e. generally) square, substantially (i.e. generally) rectangular, substantially (i.e. generally) triangular, substantially (i.e. generally) pentagonal, substantially (i.e. generally) circular or substantially (i.e. generally) oval in shape.
  • the upper surface of the base has at least one base side wall projecting therefrom.
  • base side wall refers to a wall that projects (i.e. sticks out) from the upper surface of the base at an angle, such that the base side wall is in a different plane to the upper surface of the base.
  • the at least one base side wall projects orthogonally out from the upper surface of the base.
  • the at least one base side wall may originate/ project from the edge of the upper surface of the base, or may originate/ project from any part of the upper surface of the base.
  • the at least one base side wall is continuous, but it may also be
  • a base side wall may project out from the edge of the upper surface of the base in a continuous manner to form a sample receiving area (e.g. a well).
  • the upper surface of the base may have one or more base side walls.
  • Examples of a conventional upper surface of a base having one or more base side walls include Petri- dishes (one base side wall), and 2, 4, 6, 12, 24, 48, or 96, etc well plates (multiple base side walls), all of which are intended to be encompassed herein.
  • the base side wall consists of a single wall layer.
  • the presence of a single wall layer increases the overall size of the sample receiving area(s) of the base compared to a base with a base side wall consisting of two wall layers.
  • the base side wall may also include a plurality of (i.e. two or more) areas in which the diameter of the side wall is thickened relative to the diameter of the rest of the side wall. Such areas may provide additional localized base side wall strength, and may be included in areas of the base side wall which are likely to be subjected to additional forces (e.g. areas which may be grasped by robotics).
  • the base of the present invention is configured such that the upper surface of the base and the at least one base side wall define at least one sample area.
  • the at least one sample receiving area is suitable for receiving a sample comprising at least one cell.
  • sample receiving area refers to any surface area or receptacle capable of receiving (e.g. containing) a sample containing at least one cell.
  • the sample receiving area is thus an interior cavity of the base.
  • An example of a conventional sample receiving area is a well e.g. a microtitre well.
  • the base may comprise a single (i.e. one) sample receiving area, or may comprise a plurality of sample receiving areas.
  • a base may comprise 1 , 2, 4, 6, 12, 24, 48, 96, 384, 1536 etc sample receiving areas.
  • Each sample receiving area acts as an individualized receptacle for a particular sample (e.g. a sample comprising at least one cell).
  • the shape, size and number of sample receiving areas in the base of the device can be varied depending on user preference, the desired application, and other factors.
  • the phrase "culturing at least one cell” refers to growing and/or maintaining one or more cells.
  • the phrase “culturing at least one cell” is intended to encompass culturing of tissues and whole organisms, as tissues and organisms are a higher organisation of cells.
  • the cell may be any cell and includes but is not limited to a plant cell, a fungal cell (e.g. a yeast cell), a microbial cell, a bacterial cell and a mammalian cell. Cells can be grown or cultured in the manner with which the skilled worker is familiar, depending on the cell type.
  • the culturing of mammalian cells has become a routine procedure and cell culture conditions which allow cells to proliferate are well defined.
  • cell culture of mammalian cells requires a sterile vessel (such as the device of the invention), defined growth medium and, in some examples, feeder cells and serum, typically calf serum.
  • FIG. 1 A preferred embodiment of a base in accordance with the invention is illustrated in Figure 1 (not to scale).
  • FIG. 1A a plan view of the upper surface (1) of a base is shown.
  • a continuous outer ridge (2) around the periphery of the lower surface of the base is shown, which has a larger footprint than the surface area of the upper surface (1) (or lower surface) of the base.
  • Two orientation indicators (3) are also shown as chamfered corners.
  • the base side wall (4) includes thickened areas (5) to facilitate handling by a robot.
  • FIG. 1 B a side view of the base of Figure 1A is shown, together with the relative positions of the upper surface (1) of the base and the lower surface (6) of the base.
  • the thickened area (5) is seen from the side.
  • the base side wall (4) is shown, with the top of the base side wall (4a) marked.
  • One orientation indicator (3) is also depicted.
  • FIG. 1C a plan view of the lower surface (6) of the base of Figure 1 A is shown.
  • the footprint provided by the continuous outer ridge (2) is shown.
  • a plurality of spacing elements (7) are also shown. Autoclaving two or more bases in a stacked configuration
  • the base of the invention consists of an autoclavable material and is configured for autoclaving in a stacked configuration with one or more identical bases.
  • the lower surface (e.g. Figure 1 B, (6)) of the base is configured to enable air flow (and more specifically, the flow of steam) between the base and the one or more identical bases when a plurality of identical bases is placed in a stacked configuration.
  • any configuration of the base that enables air flow between the base and one or more identical bases when a plurality of identical bases is placed in a stacked configuration is encompassed by the present invention.
  • the top of the base side wall e.g. Figure 1 B, (4a)
  • the part of the base side wall furthest away from the upper surface of the base; or in other words, the surface of the base side wall that comes into contact with an adjacent base in a stacked configuration) may also be configured to enable air flow between the base and the one or more identical bases when a plurality of identical bases is placed in a stacked configuration.
  • Various different modifications to the base may be made to enable sufficient air flow between the stacked bases, all of which are intended to be
  • air flow (and more specifically, the flow of steam) between identical bases in a stacked configuration ensures that the bases do not become damaged (e.g. explode or develop fractures) and that efficient sterilization is achieved during autoclaving.
  • the base of the invention is therefore structured to enable sufficient air flow between the stacked bases to prevent or minimize damage to the base during autoclaving in a stacked configuration.
  • the plurality of identical bases is placed in a container in a stacked configuration.
  • the container is suitable for autoclaving.
  • a plurality of bases may be placed in a stacked configuration in a container, autoclaved in the container and optionally stored after autoclaving in the container without
  • sufficient air flow between identical bases in a stacked configuration is provided by the lower surface (e.g. Figure 1 B, (6)) of the base having (or including) a plurality of spacing elements (e.g. Figure 1 C, (7)) to spatially separate the lower surface of the base from a base side wall (e.g. Figure 1 B, (4)) of an adjacent identical base when a plurality of identical bases are placed in a stacked configuration.
  • a plurality of spacing elements e.g. Figure 1 C, (7)
  • spacing element refers to any element that is capable of separating two parts or surfaces from each other (i.e. such that they are no longer in direct contact with each other).
  • a spacing element includes, but is not limited to a protrusion, an abutment, a ridge etc.
  • the spacing elements are positioned at the periphery of the lower surface of the base and project from the lower surface of the base (see e.g. Figure 1 C).
  • the spacing elements are located in a manner that facilitates stacking of a plurality of identical bases (e.g. the spacing elements are located at regular intervals around the periphery of the lower surface of the base to increase the stability of a stacked configuration).
  • the spacing elements on the lower surface of the base engage or come into contact with the top of the base side wall of the adjacent base (i.e. the surface of the base side wall that is furthest away from the upper surface of the base).
  • the base further comprises an outer ridge (e.g.
  • Figure 1 A (2) (or a plurality of outer ridges) on the lower surface of the base configured to prevent or minimize lateral movement of adjacent identical bases relative to each other when a plurality of identical bases are placed in a stacked configuration.
  • the outer ridge increases the stability of the stacked bases such that when two or more identical bases are placed one on top of the other the bases are more likely to remain stacked than they are likely to topple over.
  • the outer ridge projects from the edge of the lower surface of the base, for example as a continuous (or discontinuous) ridge around the periphery of the lower surface of the base.
  • the ridge may extend, for example, around the entire periphery of the base.
  • the ridge may generate a footprint that is slightly larger in surface area than the footprint provided by the base side wall.
  • the outer ridge projecting from the lower surface of the base provides a sufficiently large footprint to ensure that when the base is in a stacked configuration with an adjacent identical base, the outer ridge on the lower surface of a base encloses (e.g.
  • the spacing elements located on the lower surface of the base are located adjacent the outer ridge on the lower surface of the base.
  • a base (and/or a lid) of the invention may further comprise at least one orientation indicator for orienting the lid relative to the base (see e.g. Figure 1A, (3)). This facilitates placement of the lid on the base, when or if, for example, the lid is removed and replaced on the base one or more times during use (for example, when culture media is added or removed).
  • An orientation indicator may be located at any position on the base and/or lid provided that it is readily visible in use.
  • An example of a conventional orientation indicator is a chamfered corner.
  • other orientation indicators may also be used within the invention, for example one or more letters, numbers, symbols, and/or combinations thereof.
  • a base (and /or a lid) of the invention may further comprise a barcode.
  • Barcodes provide a mechanism for uniquely identifying a specific lid and/or base, and are especially useful when lids, bases and/or devices are used in conjunction with a robot.
  • manual addition of a barcode to a sterile lid, base and/or device may compromise sterility.
  • barcodes may be added to the lid/base and/or device of the invention prior to autoclaving.
  • any known barcode compatible with the autoclaving process e.g. pens, stickers with barcodes
  • the invention provides a lid comprising an upper face and a lower face, the lower face having at least one lid side wall projecting therefrom, the lid side wall being for mounting against a base side wall of a base of the invention to enclose at least one sample receiving area.
  • a “lid” refers to any device that encloses, covers or seals the mouth of at least one sample receiving area in a base.
  • the upper face and lower face of the lid form the two opposing surfaces of a
  • top of the lid i.e. the upper face and the lower face in combination, and anything in between
  • the top of the lid must be sufficiently strong for the intended purpose without significant bending, warping, or flexing.
  • Factors influencing the strength of the top of the lid include the material used and the thickness used. Those of ordinary skill in the art will recognise how to select suitable materials and/or thicknesses to provide the desired strength and rigidity.
  • the lid may be configured in a wide range of shapes and sizes.
  • the lid may be, but is not limited to being, substantially (i.e. generally) square, substantially (i.e. generally) rectangular, substantially (i.e. generally) triangular, substantially (i.e.
  • the base and lid are substantially (i.e. generally) the same shape or a complementary shape such that the lid is suitable for mounting against the base.
  • the lid may generally correspond in shape i.e. may also be substantially rectangular. It is standard in the industry for a lid to fit (e.g. be mounted against) a base using a substantially close fit.
  • the lower face of the lid has at least one lid side wall projecting therefrom.
  • lid side wall refers to a wall that projects (i.e. sticks out) from the lower face of the lid at an angle, such that the lid side wall is in a different plane to the lower face of the lid.
  • the at least one lid side wall projects orthogonally out from the lower face of the lid.
  • the at least one lid side wall may originate/ project from the edge of the lower face of the lid, or may originate/ project from any part of the lower face of the lid.
  • the at least one lid side wall is continuous, but it may also be discontinuous.
  • a lid side wall may project out from the edge of the lower face of the lid in a continuous manner such that when the lid side wall is mounted against a base side wall of a base, the at least one sample area of the base is enclosed.
  • the lower face of the lid may have one or more lid side walls.
  • the lower face of the lid may have (but is not required to have) a plurality of lid side walls when the corresponding base has a plurality of sample receiving areas.
  • the lid side wall consists of a single wall layer.
  • the phrases "mounted against” and “for mounting against” refer to the relationship between the base and the lid when the base and the lid are in a stacked configuration (i.e. when the lid is placed against the base).
  • the lid encloses the at least one sample receiving area of the base.
  • the phrase "encloses” refers to the lid as a whole obstructing or covering the mouth of the sample receiving area in the base.
  • the mouth of the at least one sample receiving area is considered enclosed (or covered etc) when contamination of the sample receiving area from external sources is minimized or prevented, and/or evaporation from the sample receiving area is minimized or prevented.
  • air/gas exchange between a sample receiving area and the external environment surrounding a device may be used to maintain e.g. the pH of culture medium or other reagents present in the sample receiving area.
  • the lid side wall sufficiently surrounds the periphery of the base side wall to enclose the at least one sample receiving area of the base.
  • FIG. 2 A preferred embodiment of a lid in accordance with the invention is illustrated in Figure 2 (not to scale).
  • Figure 2A a plan view of the upper face (8) of a lid is shown.
  • a plurality of ridges (9) is shown.
  • a plurality of spacing elements (10) are also shown at the periphery of the upper face of the lid.
  • a spacing element (10) and a ridge (9) together form a "T" shape member at the periphery of the upper face of the lid.
  • Two orientation indicators (3) are also shown.
  • FIG. 2B a side view of the lid of Figure 2A is shown, together with the relative positions of the upper face (8) of the lid and the lower face (12) of the lid.
  • the spacing elements (10) and ridges (9) are shown in profile.
  • One orientation indicator (3) is depicted.
  • FIG 3A a plan view of the lower face (12) of the lid of Figure 2A is shown. A plurality of spacing elements (13) is shown. Two orientation indicators (3) are also depicted.
  • FIG. 3B a side view of the lid of Figure 3A is shown.
  • the relative positions of the upper face (8) of the lid and the lower face (12) of the lid are illustrated.
  • the spacing elements (13) are shown in profile.
  • the ridges (9) and spacing elements (10) of Figure 2A are also shown on the upper face of the lid.
  • the lid of the invention consists of an autoclavable material and is configured for autoclaving when the lid side wall is mounted against a base side wall of a base (i.e. the lid and base are in a stacked configuration).
  • the lower face of the lid is configured to enable air flow between the lid and the base when the lid side wall is mounted against the base side wall in a stacked configuration.
  • any configuration of the lid or base that enables air flow between the lid and the base when the lid side wall is mounted against the base side wall in a stacked configuration is encompassed by the present invention.
  • the top of the base side wall i.e.
  • the part of the base side wall furthest away from the upper surface of the base; or in other words, the surface of the base side wall that comes into contact with the lower face of the lid when the lid is mounted against the base) may also be configured to enable air flow between the lid and the base when they are placed in a stacked configuration.
  • Various different modifications may be made to the base or the lid to enable sufficient air flow between the lid and base when in stacked configuration, all of which are intended to be encompassed herein.
  • air flow (and more specifically the flow of steam) between a lid and base in a stacked configuration ensures that the device does not become damaged (e.g. explode or develop fractures) and that efficient sterilization is achieved during autoclaving.
  • the lid of the invention is therefore structured to enable sufficient air/steam to flow between the lid and base in the device (when the lid is mounted against the base) to prevent or minimize damage to the lid and base during autoclaving in a stacked configuration.
  • the lid and base is placed in a container in a stacked configuration.
  • the container is suitable for autoclaving.
  • a lid and base may be placed in a stacked configuration in a container, autoclaved in the container and optionally stored after autoclaving in the container without compromising sterility. This may also minimize the space used in the autoclave by the stacked configuration.
  • sufficient air flow between the lid and base in a stacked configuration is provided by the lower face (e.g. Figure 3A, (12)) of the lid having (or including) a plurality of spacing elements (e.g. Figure 3A, (13)) to spatially separate the lower face of the lid from the base side wall (see e.g. Figure 1 B, (4)) when the lid side wall is mounted against the base side wall in a stacked configuration.
  • a spacing element is defined above.
  • the spacing elements are positioned adjacent the lid side wall and project from the lower face of the lid (see e.g. Figure 3A or 3B, (13)).
  • the spacing elements also partially extend down the lid side wall (i.e. they project from the lower face of the lid and also project from the lid side wall at the juxtaposition between the lid side wall and the lower face of the lid). Also preferably, the spacing elements are located in a manner that facilitates stacking of a plurality of identical lids (e.g. the spacing elements are located at regular intervals around the periphery of the upper face of the lid to increase the stability of a stacked configuration).
  • the spacing elements on the lower face of the lid engage or come into contact with the top of the base side wall (see e.g. Figure 1 B, (4a)) (i.e. the surface of the base side wall that is furthest away from the upper surface of the base).
  • the lower face of the lid being spatially separated from the top of the base side wall, generating a plurality of gaps between adjacent spacing elements to permit air or steam exchange between the sample receiving area(s) and the surrounding environment.
  • the lid of the invention consists of an autoclavable material and is configured for autoclaving in a stacked configuration with one or more identical lids.
  • the upper face of the lid is configured to enable air flow between the lid and one or more identical lids when a plurality of identical lids is placed in a stacked configuration.
  • any configuration of the lid that enables air flow between the lid and one or more identical lids when a plurality of identical lids is placed in a stacked configuration is encompassed by the present invention.
  • the bottom of the lid side wall i.e.
  • the part of the lid side wall furthest away from the lower face of the lid; or in other words, the surface of the lid side wall that comes into contact with an adjacent lid in a stacked configuration) may also be configured to enable air flow between the lid and the one or more identical lids when a plurality of lids is placed in a stacked configuration.
  • Various different modifications to the lid may be made to enable sufficient air flow between the stacked lids, all of which are intended to be encompassed herein.
  • air flow (and more specifically, the flow of steam) between identical lids in a stacked configuration ensures that the lids do not become damaged (e.g. explode or develop fractures) and that efficient sterilization is achieved during autoclaving.
  • the lid of the invention is therefore structured to enable sufficient air (or steam) to flow between the stacked lids to prevent or minimize damage to the lid during autoclaving in a stacked configuration.
  • the plurality of identical lids is placed in a container in a stacked configuration.
  • the container is suitable for autoclaving.
  • a plurality of lids may be placed in a stacked configuration in a container, autoclaved in the container and optionally stored after autoclaving in the container without compromising sterility. This may also minimize the space used in the autoclave by the stacked configuration.
  • sufficient air flow between identical lids in a stacked configuration is provided by the upper face of the lid (see e.g. Figure 2A, (8)) having (or including) a plurality of spacing elements (see Figure 2A, (10)) to spatially separate the upper face of the lid from the lid side wall of an adjacent identical lid when a plurality of identical lids is placed in a stacked configuration.
  • a spacing element as used herein is defined above.
  • the spacing elements are located (or positioned; the terms “located” and “positioned” are used interchangeably herein) at the periphery of the upper face of the lid (see e.g. Figure 2A). Also preferably, the spacing elements are located in a manner that facilitates stacking of a plurality of identical lids (e.g. the spacing elements are located at regular intervals around the periphery of the upper face of the lid to increase the stability of a stacked configuration).
  • the spacing elements on the upper face of the lid engage or come into contact with the bottom of the lid side wall of the adjacent lid (i.e. the surface of the lid side wall that is furthest away from the lower face of the lid).
  • the upper face of the lid being spatially separated from the bottom of the lid side wall of the adjacent lid, generating a plurality of gaps between adjacent spacing elements to permit air or steam to penetrate between the stacked lids.
  • the lid further comprises a plurality (i.e. two or more) of ridges (see e.g. Figure 2A, (9)) on the upper face of the lid configured to prevent or minimize lateral movement of two adjacent identical lids relative to each other when a plurality of identical lids is placed in a stacked configuration.
  • the ridges increase the stability of the stacked lids such that when two or more identical lids are placed one on top of the other, the lids are more likely to remain stacked than they are likely to topple over.
  • the plurality of ridges project from near the edge of the upper face of the lid, but do not abut the edge of the upper face of the lid itself (see e.g. Figure 2A).
  • the ridges form a discontinuous ridge near to (but not abutting) the periphery of the upper face of the lid.
  • the ridges together may generate a footprint that is slightly smaller in surface area than the footprint provided by the lid side wall.
  • the ridges on the upper face of the lid provide a sufficiently small footprint to ensure that when the lid is in a stacked configuration with an adjacent identical lid, the ridges on the upper face of the lid are encompassed within a lid side wall of the adjacent lid, thereby preventing or minimizing lateral movement of the adjacent identical lids relative to each other.
  • the spacing elements e.g.
  • Figure 2A, (10)) located on the upper face of the lid abut the periphery of the upper face of the lid.
  • the ridges (e.g. Figure 2A (9)) on the upper face of the lid are located adjacent the spacing elements (relatively inward of the periphery).
  • a spacing element and an outer ridge are aligned to form a T-shape member at the periphery of the upper face of the lid (see for example Figure 2A).
  • a device wherein the lid and the base consist of an autoclavable material and the lid is configured such that the device is for autoclaving in a stacked configuration with one or more devices.
  • spacing elements e.g. Figure 2A, (10) located on the upper face of a lid (as described in detail above) may also be used to enable air flow between a plurality of devices when placed in a stacked configuration (e.g. to spatially separate the upper face of the lid from a lower surface of a base in an adjacent identical device when a plurality of identical devices is placed in a stacked configuration).
  • a plurality of ridges e.g.
  • Figure 2A (9) located on the upper face of a lid may also be used to prevent or minimize lateral movement between a plurality of devices when placed in a stacked configuration (e.g. to prevent or minimize lateral movement of adjacent identical devices relative to each other when a plurality of identical devices is placed in a stacked configuration).
  • the plurality of devices is placed in a container in a stacked configuration.
  • the container is suitable for autoclaving.
  • a plurality of devices may be placed in a stacked configuration in a container, autoclaved in the container and optionally stored after autoclaving in the container without compromising sterility. This may also minimize the space used in the autoclave by the stacked configuration.
  • the invention thus provides a method of generating a stacked configuration of two or more devices of the invention.
  • the method comprises the steps of:
  • the invention provides a method of generating a stacked configuration of two or more lids of the invention, the method comprising the steps of:
  • the invention provides a method of generating a stacked configuration of two or more bases of the invention, the method comprising the steps of:
  • the invention also provides a method of autoclaving a plurality of lids, and/or bases of the invention, the method comprising:
  • Protocol 1 New plates
  • Protocol 2 Used plates (No detergent method)
  • agar medium is removed from the plate using a plastic spatula or eppendorf tip.
  • the bases are soaked in Virkon for a minimum of 20 min.
  • Protocol 3 Used Plates (Detergent method)

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Abstract

Cette invention concerne un dispositif permettant de cultiver au moins une cellule comprenant : a) une base comportant une face supérieure et une face inférieure, la face supérieure étant constituée d'au moins une paroi latérale de base qui en dépasse, la face supérieure de la base et ladite paroi latérale de base définissant au moins une zone recevant un échantillon, b) un couvercle comportant une face supérieure et une face inférieure, la face inférieure étant constituée d'au moins une paroi latérale qui en dépasse, ladite paroi latérale du couvercle servant à toucher la paroi latérale de base de manière à fermer ladite zone recevant l'échantillon, ladite base et/ou ledit couvercle (i) étant constitué(e) d'un matériau autoclavable ; et (ii) étant conçu(e) pour être autoclavable selon une configuration empilée.
PCT/GB2013/052000 2012-07-27 2013-07-26 Dispositif de culture cellulaire autoclavable WO2014016607A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB1213450.8 2012-07-27
GB201213450A GB201213450D0 (en) 2012-07-27 2012-07-27 Cell culture devices

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WO2014016607A1 true WO2014016607A1 (fr) 2014-01-30

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4406614A1 (de) * 1994-03-01 1994-10-13 Antoni Roland Dipl Ing Fh Wiederverwendbares analytisches Untersuchungssystem
US5952191A (en) * 1997-10-01 1999-09-14 Morozov; Alexei M. Method of growing several samples of microorganisms on a single flat surface of solid growth medium
FR2820432A1 (fr) * 2001-02-06 2002-08-09 Thierry Roger Garcia Dispositifs de securite pour le prelevement de micro-organismes dans l'air
US20060281172A1 (en) * 2005-05-30 2006-12-14 Kosuke Kuwabara Cell culturel vessel, production process thereof and cultured cell
US20120125936A1 (en) * 2010-11-22 2012-05-24 Byers Industries, Inc., Culturing container with filter vents

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4406614A1 (de) * 1994-03-01 1994-10-13 Antoni Roland Dipl Ing Fh Wiederverwendbares analytisches Untersuchungssystem
US5952191A (en) * 1997-10-01 1999-09-14 Morozov; Alexei M. Method of growing several samples of microorganisms on a single flat surface of solid growth medium
FR2820432A1 (fr) * 2001-02-06 2002-08-09 Thierry Roger Garcia Dispositifs de securite pour le prelevement de micro-organismes dans l'air
US20060281172A1 (en) * 2005-05-30 2006-12-14 Kosuke Kuwabara Cell culturel vessel, production process thereof and cultured cell
US20120125936A1 (en) * 2010-11-22 2012-05-24 Byers Industries, Inc., Culturing container with filter vents

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