WO2017216237A1 - Interface d'alimentation en fluide équipée d'un dispositif de lavage à contre-courant, utilisation d'une telle interface d'alimentation en fluide - Google Patents

Interface d'alimentation en fluide équipée d'un dispositif de lavage à contre-courant, utilisation d'une telle interface d'alimentation en fluide Download PDF

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Publication number
WO2017216237A1
WO2017216237A1 PCT/EP2017/064568 EP2017064568W WO2017216237A1 WO 2017216237 A1 WO2017216237 A1 WO 2017216237A1 EP 2017064568 W EP2017064568 W EP 2017064568W WO 2017216237 A1 WO2017216237 A1 WO 2017216237A1
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WO
WIPO (PCT)
Prior art keywords
supply
fluid
valve
disposal
coupling
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Application number
PCT/EP2017/064568
Other languages
German (de)
English (en)
Inventor
Oliver Kühne
Original Assignee
Hamilton Bonaduz Ag
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Publication date
Application filed by Hamilton Bonaduz Ag filed Critical Hamilton Bonaduz Ag
Publication of WO2017216237A1 publication Critical patent/WO2017216237A1/fr

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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
    • C12M23/40—Manifolds; Distribution pieces
    • 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
    • C12M33/00—Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus
    • C12M33/04—Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus by injection or suction, e.g. using pipettes, syringes, needles
    • C12M33/07—Dosage or metering devices therefore
    • 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
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation

Definitions

  • the present invention relates to a fluid supply interface for a cell culture system, the fluid supply interface comprising:
  • At least one disposal coupling formation for coupling each one of the supply fluid line different disposal fluid to the
  • At least one supply valve through which depending on its position, a supply coupling formation of fluid can flow or is blocked for a flow
  • At least one disposal valve which differs from the supply valve, through which, depending on its position, a disposal coupling formation of fluid can flow through or is blocked for a throughflow.
  • Such a fluid supply interface is known from DE 10 2013 201 069 A1. It serves to manage a plurality of cell culture containers, ie to provide them with nutrient media, to dispose of used media, optionally to clean the cell culture containers and to harvest cells of a finished cultivated cell culture at the end of a cultivation cycle.
  • the fluid supply interface allows light the successive coupling of different cell culture container to the consumer coupling formation, so that with a single fluid supply interface a variety of cell culture containers can be managed. With the fluid supply interface mentioned above cell cultures can be managed extremely economically. Decisive for the success, however, is that there is no cross-contamination between the cell culture containers managed by a common fluid supply interface. Serve for this purpose, the said valves, which allow the separation of a fluid line from the fluid channel.
  • a generic fluid supply interface which is coupled to a backwash device through which one and the same fluid in the fluid channel to the flow in opposite directions can be driven.
  • the fluid channel may be filled with cleaning fluid, and then the cleaning fluid column present in the fluid channel may be moved in opposite directions to provide mechanical cleaning action through fluid movement in addition to the chemical cleaning action due to the fluid composition, avoiding any flow shadow areas into which a cleaning fluid would flow only insufficiently in flow in only one direction of movement.
  • the cleaning fluid is only a particularly preferred example.
  • the use of the backwash device should not be limited thereto.
  • the backwashing device comprises a direction reversible pump.
  • This may be a reversible, continuously operating pump, or it may be - and this is preferred because of the achievable precise fluid movement - a piston-cylinder arrangement.
  • the piston can, for example, be driven by a rotating eccentric drive for reciprocating movement in the cylinder, wherein it moves the liquid column present in the fluid channel depending on the respectively prevailing piston movement in one or in the opposite other direction.
  • a backwash fluid line which connects the direction-reversible pump to the fluid channel to be provided upstream of the supply valve in the supply flow direction from the supply coupling formation to the consumer coupling formation.
  • the at least one supply valve is preferably pre-loaded into a blocking position preventing the flow through the supply coupling arrangement assigned to it in order to avoid undesired access to the fluid channel.
  • the supply valve is preferably pre-loaded by magnetic force into the blocking position. This also serves the hygiene of the device, because with less component count also decreases the risk of contamination in the fluid supply interface.
  • the at least one supply valve is preferably designed such that, due to sufficiently high pressure difference on both sides of the supply valve against the, preferably magnetic, biasing force for flow in the direction of the Versor- coupling connection formation opens to the fluid channel.
  • This can be realized with a magnetic preload in the blocking position structurally particularly simple.
  • the disposal valve can be biased in a closed flow preventing its closed position.
  • the disposal valve is biased by a magnetic or mechanical biasing device, by an elastomeric or metallic spring means in the closed position, it is for targeted non-contact and therefore high-purity operation of the disposal valve advantageous if it by changing an external magnetic field between its operating positions: Closed position and flow position, can be switched.
  • the externally applied to the disposal valve magnetic field and the biasing device of the disposal valve must therefore be coordinated so that the force exerted by the external magnetic field on the at least one disposal valve force can overcome the biasing force in the closed position.
  • the use of helical compression springs as a mechanical biasing device of the disposal valve is advantageous.
  • the disposal valve may comprise a displaceable actuator, which is displaced by the external magnetic field and in turn moves in its displacement a valve body of the disposal valve from the closed position to the flow position.
  • a displaceable actuator which is displaced by the external magnetic field and in turn moves in its displacement a valve body of the disposal valve from the closed position to the flow position.
  • the supply valve Regardless of the design of the disposal valve, this is also preferably by changing an external magnetic field between its operating positions: blocking position and passage position, switchable to set from the outside targeted a desired operating position can. Also, the supply valve therefore has the above Reasons preferred a valve body with or made of ferromagnetic and / or permanent magnetized material.
  • the change of an external magnetic field can be effected by changing an energization state of an electromagnet sufficiently close to the respective valve or by approaching and removing a permanent magnet to the valve.
  • the use of an approachable and removable permanent magnet is preferred over the use of an electromagnet because the electromagnet can generate a heat source when energized, which is undesirable in the case of using thermally sensitive fluids or thermally sensitive cells.
  • two sides of a valve are one side in the flow direction in front of a valve body and one side in the flow direction behind the valve body.
  • the presently presented fluid supply interface preferably serves for the management of cell culture containers of a cell culture system
  • a corresponding at least partially complementary consumer negative feedback formation of a cell culture container is temporarily coupled to the consumer coupling formation.
  • the consumer negative feedback formation is connected to the cell culture vessel via a consumer fluid line.
  • the fluid channel interconnecting the fluid supply interface coupling formations referred to in the present application may thus serve as a reference for describing flows through the supply interface. If the fluid channel has a spatially excessive extent in order to serve as a suitable reference location in an individual case, the at least one consumer coupling formation can serve as the reference location. If several consumer coupling formations are provided, for example because more than one consumer cell is present at each cell culture container. is formed against coupling formation, one of the plurality of consumer coupling information can be arbitrarily selected, wherein only care must be taken that is then used for within a Judgmentstat suitss always the same consumer coupling formation of the fluid supply point.
  • the at least one consumer coupling formation is configured for the purpose of merely temporary coupling of a consumer negative feedback formation
  • the at least one supply coupling formation and the at least one disposal coupling formation are preferably designed for the permanent coupling of a supply or disposal fluid line.
  • the training for "permanent” coupling is not to be understood that the respective fluid line can only be separated destructive of their coupling formation.
  • “Permanent” in the sense of the present application the coupling of a fluid line to the coupling formation already when it can be solved for repair and maintenance purposes of the coupling formation, but remains permanently connected to the supply point during normal operation of the supply interface, while the Consumer coupling formation is repeatedly coupled with Stereonochplungsformationen different cell culture container.
  • the supply or / and the Entsorgungskopplungsformation can be formed, for example, by pipe sockets on which a hose or a pipe end can be pushed and secured by a suitable securing means, such as hose clamps and the like, against peeling.
  • said coupling formations can also be formed by hose or pipe coupling components, one of which is provided on the supply or the disposal coupling formation and the other on the associated fluid line, so that they can be connected together to form a continuous fluid line.
  • the fluid channel can be formed in a simple but flexible construction of the fluid supply interface by a hose into which the lines coupled to the at least one supply and the at least one disposal coupling formation open.
  • the fluid supply interface for coupling to different cell culture containers preferably by a handling device, such as a multi-axis robot, is movable to different coupling locations, it is preferred if the fluid channel and thus the fluid supply interface is formed as stiff as possible.
  • the fluid supply interface therefore preferably has a substantially rigid housing in which the fluid channel is formed.
  • the consumer coupling formation may preferably be integrally formed on the housing.
  • the at least one supply coupling formation and / or the at least one disposal coupling formation can be formed integrally with the housing or mounted as formation assemblies in corresponding receptacles on the housing. The latter is preferred for reasons of simpler manufacture of the fluid supply interface.
  • At least one part, preferably all supply and / or disposal valves, are preferably located in the housing.
  • the housing may be designed in several parts to realize, for example, complex housing designs. Preferably, however, the housing is integrally formed.
  • the fluid channel can basically have any profile in the fluid supply interface and in particular in its housing, a fluid channel with a straight course is advantageous for the fluid supply interface according to the invention, at least with a rectilinear profile between the supply coupling formation furthest from the at least one consumer coupling formation furthest from the same at least one consumer coupling formation provided Entsorgungskopplungsformation.
  • the fluid channel is preferably formed either as a rectilinear blind hole in the housing of the fluid supply interface, which is preferably closed at its opening side by a plug or the like or closed by a valve, or is formed by a through hole passing through the housing, on one or both Closed longitudinal ends in the housing or can be closed by a valve.
  • the blind hole as well the passage opening can be made simple in terms of manufacturing technology and therefore advantageously as bores.
  • the at least one supply coupling formation and the at least one disposal coupling formation are preferably provided on different sides of the at least one consumer coupling formation in order to prevent a flow-mechanical conclusion between a supply coupling formation and a disposal coupling formation in which the fluid flowing between these coupling formations does not reach the consumer coupling formation.
  • the at least one supply coupling formation and the at least one disposal coupling formation are therefore preferably arranged in the fluid supply interface such that a fluid flow existing or arising between them in the fluid channel always flows past the consumer coupling formation.
  • the at least one disposal valve - as well as the at least one supply valve - have a magnetic biasing device.
  • the at least one disposal valve and the at least one supply valve have the same valve bodies.
  • the valve bodies are preferably spherical, that is to say spherical, so that their relative orientation to their surroundings in the fluid supply interface does not matter.
  • a holding formation is formed at the fluid supply interface, which holds a valve body of the supply valve in its passage position with the valve body lifted off a valve seat in the area of influence of the, preferably magnetic, prestressing force.
  • the retaining formation is in Fluid channel formed so that the valve body of the supply valve preferably lifts from its valve seat into the fluid channel into it.
  • the retaining formation is formed as a wall formation, in particular a concave, approximately negative-dome-shaped, wall formation, of the fluid channel, so that no separate components are required for this purpose.
  • the wall formation can be produced, for example, by machining a section of the housing forming the fluid channel in the region of the respectively affected valve.
  • the holding formation may extend in sections orthogonal to the direction of travel of the fluid channel in the region of the respective valve into the material defining the fluid channel.
  • machining a wall formation in the fluid channel as a holding formation for the valve body of a supply valve it is possible to use, for example, a face cutter and / or roll milling cutter, in particular ball milling cutters, shaped according to the desired wall formation.
  • the valve body of the at least one supply valve preferably already extends into the fluid channel in the blocking position of the at least one supply valve, but preferably not more than half its extent in the direction orthogonal to the fluid channel course. Thus, it can be achieved that the valve body, although flushed by a flow in the valve channel, but is not carried away by this.
  • valve body of a supply valve covers less than its greatest extent in the lifting direction, more preferably less than two thirds of its extent in the lifting direction, on its lifting position between its blocking position and its position lifted off at maximum from the valve seat. Particularly preferably, between its blocking position, in which it rests against a valve seat, and its maximum lifted position, the valve body does not rest more than half of its greatest extent in the lifting direction.
  • the maximum dimension of the valve body in any direction is always the diameter thereof.
  • the fluid channel at the discharge points of fluid lines, which open into the fluid channel, according to its design to one or both sides of the Mouth point over the confluence point away thought be continued to determine the Einragtiefe of the usually in the blocking position still in the merging fluid line valve body in the fluid channel.
  • undesirable tearing of a valve body from its valve can be prevented by making the flow cross-section of the fluid channel smaller than a cross-sectional dimension of the valve body orthogonal to the trajectory of the fluid channel in the adjoining section so that penetration of the valve body into the fluid channel is prevented.
  • the fluid channel with the lifting direction of the valve body at least one supply valve and / or at least one disposal valve an angle, preferably includes a right angle.
  • a wall portion of the fluid channel, in particular a previously described designed as a holding formation wall portion of the fluid channel, together with the valve seat to limit the movement stroke of the valve body between its operating positions serve.
  • the management of cell culture containers requires the targeted delivery of more than one fluid to a respectively coupled cell culture container and thus to the fluid supply interface, which is why it is provided that the fluid supply interface has a plurality of supply coupling formations which:
  • each are interconnected by the fluid channel and each have a supply valve which is biased into a flow-preventing blocking position, preferably by magnetic force.
  • the fluid supply interface preferably has a switching device with at least one magnet, also referred to below as a "switching magnet", through which an external magnetic field generated by the at least one magnet can be changed at a supply switching location to a supply valve provided at the supply switching location in a targeted manner between its operating positions to be able to switch.
  • a switching device By the switching device, at least a portion of the provided supply valves can be switched between their respective operating positions without contact, which minimizes or even precludes the risk of deterioration of the quality of the passed through the supply valves fluids through the switching device.
  • the present invention also includes a fluid supply interface with a plurality of supply coupling formations interconnected by the fluid channel, each having a supply valve configured as described above without any switching device.
  • a fluid supply interface with a plurality of supply coupling formations interconnected by the fluid channel, each having a supply valve configured as described above without any switching device.
  • this is not preferred since it is advantageous if a part of the supply valves can be selectively switched between their operating positions independently of the respective fluid pressure and fluid pressure difference prevailing at the valve location.
  • not all existing supply valves can be switched by the switching device. It may be sufficient to provide only those supply valves for supply fluid lines switchable by the switching device which conducts particularly sensitive fluids. Therefore, can the number of supply switching locations is less than the number of supply valves. It is all about the simultaneous switchability of supply valves. Thus, it may theoretically be conceivable for a magnet to be displaceable in such a way that it interacts with a first supply switching location for switching a first supply valve at a first time and for switching at a later second time with a second supply switching location different therefrom a second supply valve cooperates. Consequently, the first and second supply valves are not switchable simultaneously. This case also falls under the above definition that the number of supply switching points is less than the number of supply valves.
  • a supply switching location is assigned to a supply valve and therefore usually is stationary relative to the fluid channel and / or a housing of the fluid supply interface.
  • the at least one disposal valve can also be switched between its operating positions by the switching device independently of the fluid pressure prevailing at the at least one disposal valve.
  • the switching device may be necessary to manage a plurality of cell culture containers, to divert different fluids from the fluid channel or from the respectively coupled cell culture container.
  • a plurality of Entsorgungskopoppungsungsonne be provided, which are interconnected by the fluid channel and each have a disposal valve, wherein by the switching device at a disposal switching location an external magnetic field generated by the at least one magnet is variable to a disposal at the disposal Switching provided disposal valve between its operating positions to switch.
  • the number of disposal switching locations is the same as or less than the number of disposal valves.
  • a plurality of disposal valves constructively constructed as the supply valves to the supply coupling formations and has only one of these deviating function, namely at least predominantly the discharge of fluids from the fluid channel serving function.
  • the valve body preferably lifts off to the fluid channel out to switch the disposal valve in the flow position. Therefore, for such a disposal valve, what has been said above for the at least one supply valve mutatis mutandis mutatis mutandis, and in particular in connection with the holding formation to secure the remaining of the valve body at the respective valve.
  • a retaining formation designed as described above is preferably provided at the fluid supply interface.
  • the at least one disposal valve as well as the at least one supply valve on a magnetic biasing means to bias the valve body in the closed position.
  • the distance between a disposal valve and a supply valve in the longitudinal direction of the fluid channel is greater than the distance in the same direction between two disposal valves and / or between two supply valves.
  • the consumer coupling formation can be arranged between a disposal valve and a supply valve and be influenced by an external magnetic field without the risk that the magnetic field acting at the location of the consumer coupling formation, that is to say at a consumer switching location, may also be undesirably affected by a supply or a disposal valve acts and unintentionally causes a changeover of the operating position there.
  • the switching device at a consumer switching location which is located in the consumer coupling formation and on which a consumer fluid line with a consumer valve is temporarily arranged, generated by a magnet outer Magnetic field is changeable to that provided at the consumer switching point Consumer valve between its operating positions: locking position and flow position to switch.
  • a plurality of consumer coupling formations are provided, as many consumer switching locations are provided as consumer coupling formations to ensure that each consumer valve temporarily arranged on a consumer coupling formation is switchable independently of the other consumer valve.
  • the present invention further relates to the use of a fluid supply interface as described above and further developed for the management of cell culture containers, to each of which at least one consumer negative feedback formation is provided for temporary coupling to the at least one consumer coupling formation. Furthermore, the present invention relates to a cell culture management system with a fluid reservoir, with a disposal sink and with a fluid supply interface, as described above and further developed.
  • the fluid reservoir is coupled to the supply coupling formation via a supply fluid line
  • the disposal sink is coupled to the disposal coupling formation via a disposal fluid line
  • a cell culture container can be detachably connected to the at least one consumer coupling formation.
  • a cell culture container or a plurality of cell culture containers need not be part of the cell culture management system, but is preferably part of the same.
  • a fluid reservoir may comprise a container with a fluid reservoir or, for example in the case of tap water, may comprise a fluid-carrying supply line.
  • the disposal sink may comprise a container in which discarded fluid is collected from a cell culture container. This is especially the case when the fluid discharged from the cell culture container is the desired result of the cell culture.
  • it may sink to act a piping system, such as a wastewater or waste management system of a local authority, in which the cell culture management plant is operated.
  • the backwash fluid line In order to also effect a fluid movement with the backwashing device on the valve to be flushed or blocked, it is advantageous for the backwash fluid line to open in the supply or supply flow direction from the supply coupling formation to the consumer coupling formation upstream of the supply valve into the supply fluid line.
  • the backwashing device when it performs a backwashing operation, has no effect on the fluid supply, which is coupled to the same supply coupling formation as the backwash device and in which high-purity fluid is usually provided. Therefore, according to a further preferred development of the present invention, provision is made in the supply flow direction from the supply coupling formation to the consumer coupling formation upstream of the mouth of the backwash fluid line into the supply fluid line, by means of which a section of the supply fluid line located upstream of the mouth can be separated from the backwash fluid line ,
  • the indication of a direction of flow from one point to another point in a fluid line not only relates to the flow state between said points, but indicates a direction of flow which applies to each point of a fluid line fluidically connected to said points in fluid conveying connection ,
  • the cell culture management plant has a cleaning fluid reservoir as the previously mentioned fluid reservoir and additionally has at least one nutrient media reservoir as a further fluid reservoir. Furthermore, the cell culture management plant prefers In addition, a harvest sink as a further sink, is promoted in the fluid from a coupled to the fluid supply interface cell culture container to harvest finished cultured cell cultures and processed as intended can.
  • the cleaning fluid supply is then coupled to a first supply coupling formation via a first supply fluid line, wherein the first supply fluid line is preferably the supply fluid line into which the backwash fluid line opens, as described above.
  • the at least one nutrient media supply is coupled to a second supply coupling formation via a second supply fluid line.
  • Cell culture management equipment may further include one or more functional fluid supplies, such as to provide a rinse fluid to cleanse adherent cells in the cell culture container of nutrient medium, and / or to provide a release fluid to dislodge adherent cells in the cell culture container from their substrate surfaces.
  • functional fluid supplies can be coupled by third and even further supply fluid lines with third and even further supply coupling formations.
  • the disposal sink is coupled via a first disposal fluid line to a first disposal coupling formation.
  • the disposal sink serves as a so-called "waste" sink of the final disposal of a coupled to the supply interface cell culture container and / or discharged from the supply interface itself fluid.
  • the harvest sink is preferably coupled to a second disposal coupling formation via a second disposal fluid line.
  • the harvested coupling formation is preferably designed as a disposal formation for discharging fluid from a cell culture container or from the fluid supply interface, it is constructive like a supply coupling formation designed.
  • each of the existing disposal valves can be switched by the switching device between its operating positions in order to specifically discharge fluid through exactly the desired of several disposal fluid lines.
  • the supply valves preferably only that of the first supply fluid line coupled to the cleaning fluid supply can be switched by the switching device.
  • the second and each further supply fluid line it may be sufficient if they are to be opened by overpressure in the respective supply fluid line in relation to a fluid pressure prevailing in the fluid channel.
  • a third supply coupling formation may be provided which is coupled via a third supply fluid line to a wash fluid supply for purifying cultured cells of nutrient medium.
  • a fourth supply coupling formation may be provided, which is coupled to a supply of trypsin-EDTA via a fourth supply fluid line to effect detachment of adherent cells from an inner wall of a cell culture container coupled to the fluid supply interface.
  • the at least one supply coupling formation and the at least one disposal coupling formation on the one hand and the consumer coupling formation with respect to the fluid channel lie on different sides of the fluid supply interface.
  • the cell culture management system may comprise at least one pump in order to generate a positive pressure in a fluid line (usually in a supply fluid line) or a negative pressure (usually in a disposal fluid line).
  • the overpressure prevailing in a respective reservoir or the negative pressure prevailing in a respective depression can then be coupled into the connected fluid line.
  • at least one fluid reservoir opposite the fluid supply interface and the cell culture container coupled thereto against the direction of gravity can be arranged increased, so that a hydrostatic pressure difference between fluid reservoir and fluid channel is established due to the height difference between the fluid reservoir and the fluid channel.
  • the generated hydrostatic overpressure in a supply fluid line to a fluid supply can be exercised by suitable control valves on the respective connected supply valve or not exercised.
  • FIG. 1 shows a schematic and partly rough schematic sectional view through a fluid supply interface according to the invention of a likewise cell culture management system according to the invention
  • FIG. 2 shows the view of FIG. 1 with an open supply valve and likewise open consumer valve
  • FIG. 3 shows the view of FIG. 2, wherein instead of a faulty non-opened consumer valve, a disposal valve is opened by overpressure in the fluid channel,
  • Figure 4 shows the view of Figure 3, in which the disposal valve is connected by the magnet of a switching device in a flow-through position and
  • FIGS. 1 to 4 shows the view of FIGS. 1 to 4 with an opened further supply valve and the opened disposal valve, each of which is represented by a switching device are adjusted in the passage or flow-through position, for cleaning operation using a backwash device.
  • a fluid interface according to the invention is designated generally by 10. It is part of a cell culture management plant 12.
  • the fluid supply interface 10 has a preferably one-piece housing 14, which is penetrated in its longitudinal direction by a fluid channel 16, which preferably extends along a rectilinear fluid channel axis FK.
  • the fluid channel 16, which is preferably produced as a through-bore, is closed at its two longitudinal ends by a respective plug 18 at its end.
  • the fluid supply interface 10 has five supply coupling formations, which are designated below as first to fifth supply coupling formation 20, 22, 24, 26 and 28.
  • the supply coupling formations 20 to 28 are preferably of identical design, for which reason only the first supply coupling formation 20 will be described below as representative of all supply coupling formations 20 to 28.
  • the supply coupling formations 20 to 28 may, for example, have a pipe socket 30 onto which a hose 32 of a supply fluid line 34 can be pushed and secured, for example, by a hose clamp 35 against unwanted removal from the pipe socket 30.
  • the pipe socket 30 may also have a peeling aggravating the teeth.
  • Each supply coupling formation 20 to 28 is associated with a supply fluid line 34 to 42, each of which comprises a tube and can be coupled via the latter in the manner described above with the respective supply coupling formation permanently within the meaning of the present application for fluid transfer.
  • the supply fluid lines are subsequently named with the same ordinal number as the supply coupling formation to which it is connected, so that in the present example there is a first to fifth supply fluid line 34, 36, 38, 40 and 42.
  • each supply fluid line 34 to 42 is associated with a respective supply pump 44 to 52 which can increase the fluid pressure in its respective associated supply fluid line to deliver the fluid flowing through the respective supply fluid line into the fluid channel 16.
  • the supply pumps 44 to 52 are subsequently named with the same ordinal number as the supply fluid lines assigned to them, so that there is a first to fifth supply pump 44, 46, 48, 50 and 52.
  • the supply coupling formations 20 to 28 are intended to flow through fluid in the direction of supply to the fluid channel 16.
  • each supply fluid line 34 to 42 is connected to a respective fluid reservoir 54 to 62, from which via the supply pumps 44 to 52 fluids to the fluid channel 16 can be promoted.
  • the first fluid reservoir 54 may be a cleaning fluid reservoir in which water or a cleaning agent or air specifically matched to the particular cultivation case may be stored.
  • a nutrient medium with nutrients for the cells to be cultivated can be stored in the cell culture container 63.
  • a cleaning fluid such as phosphate buffered saline ("PBS"), may be stored in the third fluid reservoir 58 to clean cells of a cell culture of nutrient medium adhering thereto.
  • PBS phosphate buffered saline
  • a medium for detaching adherent cells from its surface substrate to which they adhere may be stored.
  • a medium is, for example, trypsin-EDTA.
  • the fifth fluid reservoir 62 can store a reserve nutrient medium in order to ensure an uninterrupted supply of cell cultures with nutrient medium.
  • the allocation of the fluid reservoirs 54 to 62 may of course also be different from the above-mentioned example.
  • the supply coupling formation 20, which may be formed in one or more pieces, has a supply valve 64 at its longitudinal end closer to the fluid channel 16.
  • the fluid supply interface 10 has a first to a fifth supply valve 64, 66, 68, 70 and 72 ,
  • the first supply valve 64 will be described below for all further identically constructed supply valves 66 to 72.
  • the first supply valve 64 has a spherical valve body 74, which is made of ferromagnetic, but not magnetized material. This spherical valve body 74 rests in the blocking position of the supply valve 64 on a soft-elastic valve seat 76, such as silicone elastomer, on which the valve body 74 sealingly abuts in its blocking position with slight deformation of the valve seat 76.
  • the valve body 74 is magnetically biased by an annular permanent magnet 78, which is flowed through in its central passage of fluid in the blocking position shown in Figure 1.
  • a holding formation 80 may be provided which, for example, be formed directly in the housing 14 as a formation of the wall enclosing the fluid channel 16.
  • the holding formation 80 may be formed opposite the biasing magnet 78 in the lifting direction A as a concave wall formation with respect to and within the cylindrical wall of the fluid channel 16. While the cylindrical wall of the fluid channel 16 is curved only about the course axis FK of the fluid channel 16, the holding formation 80 can additionally be curved around an axis of curvature orthogonal to both the fluid channel axis FK and the lifting direction A.
  • the second disposal coupling formation 84 is coupled via the second disposal fluid line 88 to a harvesting container 92, in which finished cultivated cell cultures can be conveyed out of the rudimentary cell culture container 63.
  • the crop container 92 may be under a relative negative pressure, or a feed pump may be disposed in the second disposal fluid line 88 to effect a flow of fluid in the direction of disposal.
  • valve body 98 For the adjustment of the valve body 98 from the closed position shown in Figure 1 in its raised from the valve seat 100 flow position of the valve body 98 is movable in an opening direction B, which is opposite to the lifting direction A of the other valve body in the example shown. Both the lifting direction A and the opening direction B are preferably collinear with the running direction of the respective fluid lines 34 to 42, 86 and 88 in the region of their connection to the fluid supply interface 10.
  • the pipe sockets 30 of the coupling formations 20 to 28, 82 and 84 are preferably parallel to each other and are all on the same side with respect to the fluid channel 16. In the area between the coupling formations 28 and 84, the greater distance between them is used to form a consumer coupling formation 104 train. To facilitate the coupling of consumers, such as cell culture containers 63 thereto, the consumer coupling formation 104 opens with respect to the fluid channel 16 to another, preferably to an opposite side as the coupling formations 20 to 28, 82 and 84.
  • the fluid supply interface 10 is further coupled to a backwashing device 110, which in the example illustrated is connected to the first supply fluid line 34, through which cleaning fluid can be conveyed into the fluid channel 16.
  • the backwash 1 10 which will be discussed in more detail below, comprises in the example shown, a piston-cylinder assembly 1 12 with a cylinder 1 in a cylinder 14 along its cylinder axis Z movable piston 1 16. This is a connected to the first supply fluid line 34 Volume 1 18 of the backwashing device 1 10 variable.
  • FIG. 3 now shows the situation of FIG. 2, wherein the consumer valve 106 was erroneously not adjusted into the flow position despite the approach of the switching magnet 124 to the housing 14 and thus to the consumer switching location 126.
  • This error can have various causes, but it does not matter here.
  • the solenoid 124 may experience jamming and therefore may be incompletely approachable to the housing 14. It is also possible that it is between the valve body and the elastomeric Material of the valve seat of the consumer valve 106 has come to unusually large clamping forces, so that the force exerted by the switching solenoid 124 is insufficient force. Finally, the solenoid 124 may have lost magnetization due to an external magnetic field.

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Abstract

L'invention concerne une interface d'alimentation en fluide (10) comprenant : au moins un système d'accouplement d'alimentation (20, 22, 24, 26, 28) utilisé à des fins d'accouplement, au moins un système d'accouplement d'évacuation, au moins un système d'accouplement de consommateur (104) sur l'interface d'alimentation en fluide (10), un canal fluidique (16) qui relie entre eux le ou les système(s) d'accouplement d'alimentation (20, 22, 24, 26, 28), le ou les système(s) d'accouplement d'évacuation (82, 84) et le ou les système(s) d'accouplement de consommateur (104), au moins une vanne d'alimentation, au moins une vanne d'évacuation, l'interface d'alimentation en fluide étant accouplée à un dispositif de lavage à contre-courant (10) permettant de commander un seul et même fluide dans le canal fluidique (16) pour le faire circuler dans des sens opposés.
PCT/EP2017/064568 2016-06-17 2017-06-14 Interface d'alimentation en fluide équipée d'un dispositif de lavage à contre-courant, utilisation d'une telle interface d'alimentation en fluide WO2017216237A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102016210850.6A DE102016210850A1 (de) 2016-06-17 2016-06-17 Fluidversorgungsschnittstelle mit Rückspülvorrichtung, Verwendung einer solchen Fluidversorgungsschnittstelle zur Bewirtschaftung von Zellkulturbehältern und Zellkultur-Bewirtschaftungsanlage
DE102016210850.6 2016-06-17

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WO2017216237A1 true WO2017216237A1 (fr) 2017-12-21

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Cited By (1)

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Publication number Priority date Publication date Assignee Title
WO2020141327A1 (fr) * 2019-01-04 2020-07-09 Oribiotech Ltd Système et dispositif pour traitement de cellules et procédés d'utilisation correspondants

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020008067A1 (fr) * 2018-07-06 2020-01-09 Ge Healthcare Bio-Sciences Corp. Dispositif et procédé d'échantillonnage
DE102020110209A1 (de) 2020-04-14 2021-10-14 Bürkert Werke GmbH & Co. KG Fluidmodul, Fluidsystem und Verfahren zum Reinigen eines Fluidmoduls

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DE3508151A1 (de) * 1985-03-07 1986-09-11 M A N Technologie GmbH, 8000 München Magnetisches schnellschlussventil
WO2011090781A1 (fr) * 2010-01-19 2011-07-28 Millipore Corporation Système collecteur d'un bioréacteur de culture cellulaire à usage unique
DE202012008382U1 (de) * 2012-08-31 2012-09-20 Eisenmann Ag Ventil zur Verwendung in einer Applikationseinrichtung
DE102012022144A1 (de) * 2012-11-12 2014-05-15 InnoCyte GmbH Sterilverbinder zur Fluidführung sowie Verbindungselemente desselben
DE102013201069A1 (de) 2013-01-23 2014-07-24 Hamilton Bonaduz Ag Zellkulturanlage zur Kultivierung adhärenter Zellen sowie Fluid-Versorgungsschnittstelle und Zellkulturbehälter für eine derartige Zellkulturanlage
DE102013112049A1 (de) * 2013-10-31 2015-04-30 Hamilton Bonaduz Ag Deckel für Zellkulturbehälter
DE102014214076A1 (de) * 2014-07-18 2016-01-21 Hamilton Bonaduz Ag Fluidleitungsanordnung, umfassend eine Mehrzahl von Fluidleitungselementen, Ventilleitungsanordnung, umfassend eine Fluidleitungsanordnung und eine Schaltanordnung, und Handhabungsanordnung mit einer Ventilleitungsanordnung

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3508151A1 (de) * 1985-03-07 1986-09-11 M A N Technologie GmbH, 8000 München Magnetisches schnellschlussventil
WO2011090781A1 (fr) * 2010-01-19 2011-07-28 Millipore Corporation Système collecteur d'un bioréacteur de culture cellulaire à usage unique
DE202012008382U1 (de) * 2012-08-31 2012-09-20 Eisenmann Ag Ventil zur Verwendung in einer Applikationseinrichtung
DE102012022144A1 (de) * 2012-11-12 2014-05-15 InnoCyte GmbH Sterilverbinder zur Fluidführung sowie Verbindungselemente desselben
DE102013201069A1 (de) 2013-01-23 2014-07-24 Hamilton Bonaduz Ag Zellkulturanlage zur Kultivierung adhärenter Zellen sowie Fluid-Versorgungsschnittstelle und Zellkulturbehälter für eine derartige Zellkulturanlage
DE102013112049A1 (de) * 2013-10-31 2015-04-30 Hamilton Bonaduz Ag Deckel für Zellkulturbehälter
DE102014214076A1 (de) * 2014-07-18 2016-01-21 Hamilton Bonaduz Ag Fluidleitungsanordnung, umfassend eine Mehrzahl von Fluidleitungselementen, Ventilleitungsanordnung, umfassend eine Fluidleitungsanordnung und eine Schaltanordnung, und Handhabungsanordnung mit einer Ventilleitungsanordnung

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020141327A1 (fr) * 2019-01-04 2020-07-09 Oribiotech Ltd Système et dispositif pour traitement de cellules et procédés d'utilisation correspondants

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