EP2384363A2 - Installation pour la culture automatisée et parallèle de cellules - Google Patents
Installation pour la culture automatisée et parallèle de cellulesInfo
- Publication number
- EP2384363A2 EP2384363A2 EP10721643A EP10721643A EP2384363A2 EP 2384363 A2 EP2384363 A2 EP 2384363A2 EP 10721643 A EP10721643 A EP 10721643A EP 10721643 A EP10721643 A EP 10721643A EP 2384363 A2 EP2384363 A2 EP 2384363A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- cell culture
- plates
- culture vessels
- gas
- wells
- Prior art date
- Legal status (The legal status 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 status listed.)
- Withdrawn
Links
Classifications
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- 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
- C12M41/48—Automatic or computerized control
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- 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
- C12M23/12—Well or multiwell plates
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- 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
- C12M23/48—Holding appliances; Racks; Supports
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- 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
- C12M23/50—Means for positioning or orientating the apparatus
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- 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
Definitions
- the present invention relates to a device for the automated, parallelized cultivation of cells in cell culture vessels, in particular microtiter plates (MT plates).
- MT plates microtiter plates
- the observation unit with a microscope and a camera enables constant observation and optical evaluation of cell growth and cell morphology.
- Cell culture vessels can be, for example, cell culture bottles.
- the cell culture vessels are MT plates.
- the MT plates are automatically filled by the fluid distribution unit or unneeded or used fluid is sucked off or replaced.
- the modules of the system are arranged in a special housing, so that the device acts as a so-called sterile bench.
- a sterile bench With this sterile bench, an open fluid and media supply is possible because the risk of bacterial contamination through the housing is greatly minimized.
- the entire device usually functions automatically, i.e., the essential steps in culturing the cells, such as e.g. Filling and aspiration of the wells (wells of the MT plates), microscopic observation and evaluation are carried out automatically.
- all the work steps can be performed in the closed system of the sterile bench and it must, for example, no MT plates are removed from the system. Due to the controllability of the climatic conditions in the device, the climate (temperature and / or gas mixture) can be adapted from the outside to the respective needs of the cell cultures.
- the device according to the invention has a climate chamber in which a desired climate, namely a desired temperature and / or a desired humidity and / or gas composition, is preferably automatically adjustable and in which the receiving device with the cell culture vessels, in particular the MT plates at least partially is integrated, wherein the climate chamber is arranged in the housing.
- the climate chamber makes it possible to create a specific climate only within a limited area within the enclosure. As a rule, all cell culture vessels used, in particular MT plates with the cell cultures located therein, are arranged inside the climate chamber.
- a specific, optimal for the respective cell cultures climate set is set.
- the temperature is preferably set to values of 20 to 45 ° C.
- the CO 2 concentration is usually set to 0 to 20%.
- the proportion of oxygen within the climate chamber is usually 10 to 40%.
- the control of the climate within the climate chamber is preferably carried out by appropriate sensors within the climatic chamber. Furthermore, it is achieved by the climate chamber that a further separation of the cell cultures from the outside world takes place and thus the danger of a bacterial contamination of the cell cultures in the cell culture vessels is further minimized.
- separate gas containers are provided which contain different gases, preferably O 2 , CO 2 and N 2 , wherein the gas streams are controllable from the gas cylinders and wherein certain amounts of gas are passed into a mixing chamber, from where the thus prepared gas mixture is passed into the climatic chamber.
- gases preferably O 2 , CO 2 and N 2
- the gas streams are controllable from the gas cylinders and wherein certain amounts of gas are passed into a mixing chamber, from where the thus prepared gas mixture is passed into the climatic chamber.
- a precisely predetermined gas mixture can be prepared and initially tested for the desired composition. Only then is the gas mixture passed from the mixing chamber into the climate chamber.
- the adjustment of a particular gas composition is particularly important in the cultivation of cells. For example, tumor cells grow at significantly less oxygen than it does in the ambient air. On the other hand, one wants to investigate, for example, damaged neuronal cells at much higher O 2 concentrations than those of the tumor cells mentioned.
- the gas mixture produced in the mixing chamber is brought to a certain temperature before it is passed into the climatic chamber.
- optimal conditions for different cells to be cultivated can be produced.
- MT plates of a different number and number of wells eg 6, 12, 24, 48, 96, 384 wells per MTP
- the cell culture vessels, in particular MT plates, preferably in the region of the observation unit and / or in the area of the fluid distribution unit, are preferably transportable automatically from the climate chamber or into the climate chamber by a carriage or robotic arm.
- certain selected cell culture vessels in particular MT plates for filling with fluid can be brought out of the climatic chamber for a short time.
- certain cell culture vessels can be transported for observation in the area of the observation unit.
- These targeted, short-term transports from the climatic chamber have no negative effects on the climate within the chamber.
- the automatic transport of the cell culture vessels from the climate chamber or into the climate chamber replaces a manual movement of the MT plates within the system, which would be associated with a high risk of contamination.
- the observation unit and / or the Fluidver Ecuadors- unit are arranged outside the climatic chamber.
- the receiving device comprises at least two receiving units, preferably arranged one above the other, and preferably has holding devices for holding the cell culture vessels, in particular MT plates.
- the stacked receiving units a serious space savings is achieved, which also leads to a reduction in system costs.
- the holding devices may be, for example, recesses within the receiving units whose shape is adapted to the shape of the cell culture vessels, in particular MT plates.
- a cell culture vessel located in the region of the observation unit, in particular MT plate can be moved, the movements preferably being controllable.
- the optics (microscope incl. Camera) of the observation unit and / or the cell culture vessel to be observed are movable, wherein the movements of the camera or of the cell culture vessels are preferably controllable.
- the microscope used in the optics of the device according to the invention can be a normal microscope (transmitted-light microscope) or else a phase-contrast microscope or any other detection device for the observation and / or analysis of cells.
- fluorescence microscopy can also be carried out with the device according to the invention, which is why it is often advantageous if the microscope is a fluorescence microscope.
- the optics of the device according to the invention preferably has an automatic focusing. Furthermore, the optics usually has an automatic lens change.
- the observation unit is preferably capable of online evaluation of cell morphology, cell physiology, cell behavior and cell growth.
- the evaluation of the data of the cell cultivations is usually carried out by a PC with a specifically created software and user interface.
- the fluid distribution unit comprises a plurality of containers for storing different fluids, such as cell solutions, nutrients and dyes, and a microdosing for targeted, controlled addition of the fluids in the cell culture vessels, in particular in the wells of the MT plates and preferably also for removing the fluids from the cell culture vessels, in particular from the wells of the MT plates, wherein the movements and actions of the microdosing unit are preferably controllable.
- the fluid distribution unit By carrying out the fluid distribution unit with a plurality of containers for storing different fluids, it is possible, for example, to add a plurality of different fluids to specific wells of MT plates. If, for example, fluorescence microscopy is to be used, dyes for fluorescence microscopy can also be introduced into some wells in addition to cell solutions and nutrients. If some wells are again to be freed from fluids, this can also be done by the microdosing unit of the fluid distribution unit.
- the containers can be positioned around the microdosing unit.
- the microdosing unit is preferably rotatable and / or raised and lowered, so that the microdosing unit can approach the individual containers by means of rotational and / or lifting and lowering movements.
- the cell culture vessels in particular MT plates and preferably also the wells of the MT plates are indicated.
- each plate and preferably each well is assigned an assignment number (index), which is recognized by the system, in particular by the software described below.
- each culture vessel is indexed for unique assignment and identification and provided with an internal index / number (for example MTP 1 to MTP 24).
- each sub-vessel of a culture vessel typically each well of an MT plate
- each pitch is indexed in the cradle (especially in the climatic chamber) for unambiguous assignment and identification (for example, pitch 1 to 24).
- the cell culture vessels are transparent.
- all types of microscopy, especially fluorescence microscopy can be performed.
- Used MT plates are preferably formed very thin, whereby the lenses of the microscope can be brought as close as possible to a cell culture to be observed.
- the MT plates may, for example, have thin film bottoms.
- the MT plates may be made of any translucent materials, such as e.g. Glass, plastic, etc. be made.
- cell culture vessels such as cell culture bottles such as T25 or T75 or closed autoflasks can be used as an alternative to MT plates.
- said different culture vessels can be used both alternatively and side by side.
- the receiving device for receiving the cell culture vessels to different adapters, through which an adaptation to different shapes and sizes of culture vessels is possible.
- these sensors have the control of all relevant parameters, in particular temperature, gas concentration, in particular CO 2 concentration, O 2 concentration, N 2 concentration, humidity and / or supply of fluids into the cell culture vessels, in particular in the wells of MT plates on. These sensors are the basis for fully automatic control and regulation of the climatic conditions as well as the supply of fluids into the cell culture vessels.
- a particularly preferred embodiment of the device according to the invention is characterized by a computer-controlled control and control system for automatic control and control of at least one, preferably all listed below parameters or steps: a) temperature, in particular in the climatic chamber; b) O 2 content in the gas, in particular in the climatic chamber; c) CO 2 content in the gas, in particular in the climate chamber; d) N 2 content in the gas, in particular in the climatic chamber; e) filling and / or draining selected cell culture vessels, in particular selected wells, of selected MT plates with selected amounts of selected fluids; f) microscopic observation and evaluation of cell cultures in selected cell culture vessels, in particular selected wells of selected MT plates at selected times with selected technique, such as fluorescence or phase contrast microscopy.
- all parameters or work steps are fed into the system.
- the climatic conditions are automatically regulated by the system. Should one or more parameters deviate from the entered values in the course of the cell cultivation cycles (eg as a consequence of a short-term opening of the climatic chamber for transporting an MT plate out or in), this will be immediately readjusted to the specified value.
- the MT plates For specific filling of selected wells of selected MT Plates with selected amounts of selected fluids are indicated as the MT plates, and preferably also the wells of the MT plates. As a result, the wells of the MT plates can be entered in a particularly simple manner in the system and recognized by this.
- the recordings are preferably stored by the system.
- the system also preferably recognizes certain changes in the cell cultures and can thereby react to certain changes in the cell cultures by readjusting the above-mentioned parameters or work steps.
- a preferred embodiment of the device according to the invention is characterized by a loading and Entdeckelungsvorraum for, preferably automatic loading and Entdeckein the cell culture vessels (see also figure description).
- a controlled selective use of disposable and multiple pipettes is possible in the fluid distribution unit. This can prevent cross-contamination between individual culture vessels and wells.
- two types of pipettes are used in the device according to the invention. So come on the one hand so-called working pipettes used, which are used several times during a cultivation, which brings the need for a sterile recording and sterile filing.
- the working pipettes are stored in sterile boxes within the device according to the invention.
- a robot arm In the area of the fluid distribution unit, a robot arm generally takes up the working pipettes in a sterile manner from the receiving boxes. Thereafter, the desired Fluid pressen be performed on the cell culture containers.
- the robot arm of the fluid distribution unit rests the working pipettes again sterile in the receiving box.
- This work cycle can take place several times during a cell cultivation.
- the inventive device usually also disposable pipettes used. These disposable pipettes are used only once during cell culture, with the need for one-time sterile ingestion and safe disposal after a one-time procedure.
- the disposable pipettes are stored in sterile disposable boxes in the area of the fluid station.
- the fluid robot arm takes a disposable pipette sterile from a receiving box.
- the desired fluid action is performed on a cell culture container, in particular an MT plate.
- the robotic arm drops the disposable pipette into a waste box. This working cycle takes place only once with a disposable pipette during a cell cultivation.
- the present invention further relates to a method for the automated, parallelized cultivation of cells in cell culture vessels, in particular microtiter plates, which are in a cell culture system, in particular in a device according to one of claims 1 to 13, comprising the following steps: a) filling the system with cell culture vessels ; b) filling the system with containers containing fluids to be used, such as cell culture medium, cell suspension, test substance, dye; c) loading the system with containers containing gases to be used, such as O 2 , CO 2 , N 2 ; d) Programming the automatic tuning system for at least one of the following parameters:
- the system automatically regulates the climatic conditions in the sense of a control loop for the constant maintenance of the climatic conditions. Furthermore, the system carries out the microscopic evaluation according to the programmed values for the microscopy.
- multiple freely selectable observation points in the culture vessel or in the subunits (for example POI 1 to 10 in the well 2 of the culture vessel 4) can be defined in each culture vessel.
- a specific control software with a user interface can freely choose which POI is to be evaluated in which culture vessel at which time and which optical method (for example transmitted light, phase contrast, fluorescence).
- each POI can be approached by the traversing unit (cross table) in three axes x-y-z (ie horizontal and vertical), focused by the system, recorded, evaluated and stored. Owing to the possibility of this three-dimensional recording and storing of POIs, different levels can be focused in a culture vessel or in a subunit of a culture vessel.
- Each POI can be approached and evaluated very accurately over time with a precision of ⁇ 1 ⁇ m.
- you can also use time-lapse photography and dynamic evaluations of each POI are made possible by composition of the individual images.
- automatic analysis of the optical image information by means of a specific software and user interface is usually possible (for example cell number, cell movement, cell shape, color information of fluorescently labeled cell components, number of stained cells).
- the system can remove used media and feed new media.
- the device according to the invention may have a further housing, which may contain the said gas cylinders.
- FIG. 1 shows a side view of a device according to the invention (without housing and climatic chamber);
- FIG. 2 is a perspective view of the device of FIG. 1; FIG.
- Fig. 3 is a plan view of the device of Fig. 1;
- FIG. 4 shows a perspective view of the device of FIG. 1 with climate chamber
- FIG. 5 shows the device of FIG. 4 with housing
- Fig. 6 control and regulation scheme for a device according to the invention.
- FIG. 7 shows a perspective illustration of a de-capping device in a device according to the invention
- FIG. 8 is a plan view of the de-capping device of FIG. 7.
- FIG. 8 is a plan view of the de-capping device of FIG. 7.
- FIG. 1 shows a side view of a device 1 according to the invention for automated, parallelized cultivation of cells in microtiter plates 2 with an observation unit 3, a recording device 4 for receiving the microtiter plates 2 and a fluid distribution unit 5.
- the observation unit 3 comprises a CCD camera 6 , and a microscope 7.
- the camera 6 and the microscope 7 are arranged on a holder 8.
- the observation unit 3 further comprises a receiving table 9 for receiving the MT plates 2.
- the receiving device 4 comprises four superimposed receiving plates 10.
- the receiving plates 10 have (not shown here) recesses into which the MT plates are fitted.
- the receiving device 4 can be raised or lowered.
- the MT Plates 2 are moved.
- it is shown how an MT plate 2a is transported by the receiving device 4 into the region of the observation unit 3 with the aid of a carriage 11.
- the fluid distribution unit 5 comprises a microdosing device 12 with a movable, in particular rotational movements and / or lifting and lowering movements exporting arm 13, which is provided with a fixed or exchangeable pipette 14.
- the fluid distribution unit further comprises a plurality of containers 15, in which different fluids, such as cell suspensions, nutrients, dyes, etc., are included.
- the containers 15 are arranged in a certain arrangement around the microdosing device 12, wherein the pipette 14 by rotational movements and / or lifting and lowering movements of the Verteilarms 13 and / or by movement of the pipette along the upper portion 16 of the Verteilarms 13 to the individual containers can be brought.
- the MT plates 2 can be automatically transported by the receiving device 4 into the region of the fluid distribution unit 5 by means of a carriage.
- an MT plate 2b is arranged in the region of the fluid distribution unit 5 and is filled there with the aid of the microdosing device 12 with specific fluids.
- FIG. 2 shows a perspective view of the device of Figure 1. Good to see in this illustration, the superimposed receiving plates 10 of the receiving device 4. The individual receiving plates 10 have recesses 18 which are dimensioned so that the MT plates 2 received therein and can be kept.
- FIG. 3 shows a plan view of the device 1 of FIG. 1 and FIG. 2. In addition to the actual working space, which is located below the housing (not shown here), a receiving chamber 19 for receiving gas cylinders 20 is arranged.
- FIG. 4 shows the device 1, wherein the receiving device 4 is arranged in a climatic chamber 21.
- the housing 21 a of the climate chamber may be transparent or opaque.
- the housing 21a encloses the receiving device 4 substantially airtight and thus contributes to avoiding contamination of the MT plates.
- a desired climate can be adjusted. For example, the temperature, the O 2 concentration, the CO 2 concentration, N 2 concentration and the air humidity can be set. In this way, the climatic conditions can be adjusted to the particular needs of the cells to be cultivated.
- the observation unit 3 and the fluid distribution unit 5 are arranged outside the climate chamber 21 and are thus not exposed to the climatic conditions which are necessary for optimum cell cultivation.
- a two openings 22 are arranged, which allow the transporting of MT plates from the climatic chamber 21 out or in the climatic chamber 21 inside.
- the openings 22 are arranged in the region of the observation unit 3 as well as in the area of the fluid distribution unit 5 and allow transport of MT plates 2 there.
- the openings 22 can be closed after the MT plates have been transported.
- FIG. 5 shows the device 1 with attached housing 23.
- the housing 23 may be completely transparent or completely opaque.
- the housing 23 can also-as in the present exemplary embodiment-have a transparent region 24 in the form of a glass pane.
- the glass pane 24 may be formed as an open window, so that, if necessary, can be passed through the open window 24 into the interior of the housing 23.
- the entire device 1 is designed as a so-called "sterile bench.”
- the housing 23 closes the cultivation space substantially airtight and prevents penetration of dirt, bacteria, etc. from the outside into the interior.
- All climatic conditions inside the climate chamber 21 and in the housing 23 are controlled by a computer-controlled control and control system. Sensors inside the housing 23 or inside the climate chamber 21 constantly provide information about the current conditions in the respective rooms. Through the control and control software, the climatic conditions are always kept at a predetermined level. Also, the filling of wells 17 of certain MT plates with certain amounts of particular fluids is controlled by the computer controlled control system. For this purpose, the MT plates (2) and the individual wells 17 of the MT plates 2 are indexed and recognized by the system. The computer controlled control system may be programmed to fill certain wells (17) of selected MT plates (2) with certain amounts of particular fluids at specific times.
- the computerized control system for microscopically observing and evaluating certain cell cultures in particular wells (17) of certain MT plates (2) at certain times with certain technique, such as e.g. Programmed fluorescence or phase contrast microscopy and / or any other detection method for observation and / or analysis of cells.
- certain technique such as e.g. Programmed fluorescence or phase contrast microscopy and / or any other detection method for observation and / or analysis of cells.
- the system can be programmed to take pictures of cell cultures at specific times, with recordings usually being stored and continually evaluated.
- FIG. 6 shows a schematic representation of the control and regulation of the climatic conditions in the interior of the climate chamber 21 and in Inside the housing 23.
- gas sensors 25 are arranged, namely a CO 2 sensor 26, an N 2 sensor 27 and an O 2 sensor, not shown here. Furthermore, sensors for other gases may be present.
- the concentration values determined by the gas sensors are fed to a climate chamber controller.
- An air humidity sensor 29 constantly detects the humidity in the interior of the climate chamber 21 or in the interior of the housing 23.
- a temperature sensor 30 continuously measures the temperature.
- the humidity sensor 29 and the temperature sensor 30 also transmit their values to the climate chamber controller 28.
- Another temperature sensor 31 constantly measures the temperature inside the housing 23.
- a so-called laminar hot air heater 32 sets a temperature in the housing, preferably the temperature in the climatic chamber corresponds, a. This prevents condensation processes in the climate chamber.
- the climate chamber controller 28 regulates the humidity in the interior of the climatic chamber 21 via a humidifier 33. Between the humidifier 33 and the climatic chamber 21, a filter element 34 is interposed. Furthermore, fresh air 35 can be introduced into the interior of the housing 23 or the climatic chamber 21.
- the gas flows from the gas cylinders 20 are controlled by gas regulators. In this case, certain amounts of gas are passed into a mixing chamber 36. Via a gas circulation pump 37, which is also regulated via the climate chamber controller 28, the desired gas mixture is passed into the climatic chamber 21. The desired gas mixture is brought to the desired temperature by a gas mixture line heater 38.
- the receiving device for receiving the MT plates can also be constructed of superposed, independently rotatable turntables.
- the individual receiving elements of the receiving device may be formed in the manner of assembly lines, through which a linear arrangement of the MT plates and a linear trans- the same port is reached.
- the climate chamber is transparent at least in the region of the observation unit and can be microscoped or observed through the wall of the climate chamber, so that the MT plates do not have to be moved out of the climate chamber.
- the climatic chamber can also have a bulge into which an MT plate to be observed can be brought in for observation.
- the positions of the MT plates are defined to be the same for each observation, i. with repeated passage, the observation position should be approached reproducibly with high accuracy.
- the accuracy of the system is dictated by the accuracy of the outside dimensions of the MT plates.
- the MT plates can be covered with a foil at the bottom and thus optically defined. However, certain deviations occur in the Z direction.
- Another embodiment of the MT plates is that the plates are equipped with a glass sheet and optically defined. These MT plates have hardly any deviations in the Z direction.
- FIG 7 shows a perspective view of a Entdeckelungsvor- direction (40) of a preferred embodiment of a device according to the invention.
- the de-capping device comprises a robot arm (41) and a lid holding device (42).
- Figure 8 shows the lid holding device (40) in a plan view.
- the Entdeckelungsvor- direction (40) is used for loading and uncovering MT plates (2).
- the MT plates are stored in the climate chamber for incubation with the lid closed. In the fluid or optical station, however, the MT plates are to be processed without a lid. Therefore, the MT plates must always be entdeckelt or what is possible with the Entdeckelungsvortechnisch (40).
- the term decapping device also includes that the device (40) is also suitable for covering. If, for example, an MT plate is to be moved from the incubator to the optics station, the robot arm (41) retrieves the corresponding MT plate from the selected place in the climate chamber ("shelf space").
- the lid holding device (42) has horizontally displaceable retaining clips (43) which are movable by means of a spring or mechanically movable pin (45)
- a spring or mechanically movable pin 45
- the lid (44) of the MT plate (2) is inserted into the holding device (42) and held by the retaining clips (43), and then the robot arm (41) moves down with the MT plate (2) the lid (44) remains in the lid holding device (42) .
- the decapping device (40) is positioned in the climatic chamber (21).
- the robot arm (41) moves the opened MT plate (2) out of the climatic chamber into the observation unit (optical station). While the MT plate remains in the observation unit for a certain time, the lid (44) is still held in the lid holding device.
- the robot arm (41) moves the open MT plate back from the optics station back into the climate chamber. There, the robot arm (41) moves the open MT plate (2) upwards in the direction of the cover holding device (42), wherein ultimately the open MT plate is accurately connected to the cover (44). Now let the retaining clips (43) the lid (44), causing the MT plate (2) is finally covered again. Now the robot arm (41) moves the MT plate down and spends it to the desired "parking space".
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Abstract
L'invention concerne une installation pour la culture automatisée et parallèles de cellules dans des récipients de culture de cellules, en particulier des plaques microtitre (plaques MT) (2) comprenant un boîtier (23) dans lequel sont disposés une unité d'observation (3) comprenant au moins un microscope (7) et au moins une caméra (6), un dispositif de réception (4) pour recevoir des récipients de culture de cellules ainsi qu'une unité de répartition de fluide (5) permettant le remplissage et le vidage automatique des récipients de culture de cellules, en particulier des puits (17) de plaques microtitre contenant des fluides, les conditions climatiques de l'installation, en particulier la composition des gaz et la température sont réglables au moins dans la zone des récipients de culture de cellules, une chambre climatisée (21) étant prévue dans le boîtier, dans laquelle peuvent être réglés une température souhaitée et/ou une composition de gaz et dans laquelle est intégré, au moins en partie, le dispositif de réception (4) avec les récipients de culture de cellules (2).
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE200910018325 DE102009018325B4 (de) | 2009-04-22 | 2009-04-22 | Vorrichtung zur automatisierten, parallelisierten Kultivierung von Zellen |
DE200920005898 DE202009005898U1 (de) | 2009-04-22 | 2009-04-22 | Vorrichtung zur automatisierten, parallelisierten Kultivierung von Zellen |
PCT/DE2010/000454 WO2010121601A2 (fr) | 2009-04-22 | 2010-04-22 | Installation pour la culture automatisée et parallèle de cellules |
Publications (1)
Publication Number | Publication Date |
---|---|
EP2384363A2 true EP2384363A2 (fr) | 2011-11-09 |
Family
ID=43011523
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP10721643A Withdrawn EP2384363A2 (fr) | 2009-04-22 | 2010-04-22 | Installation pour la culture automatisée et parallèle de cellules |
Country Status (5)
Country | Link |
---|---|
US (1) | US20120034596A1 (fr) |
EP (1) | EP2384363A2 (fr) |
JP (1) | JP2012524527A (fr) |
KR (1) | KR20110133589A (fr) |
WO (1) | WO2010121601A2 (fr) |
Families Citing this family (29)
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KR20140096051A (ko) * | 2011-10-07 | 2014-08-04 | 폴 테크놀로지 유케이 리미티드 | 유체 처리 제어 시스템 및 이와 관련된 방법 |
KR101341833B1 (ko) | 2011-10-24 | 2013-12-16 | 대한민국 | 공기전염 병원성 미생물 무인 포자채집장치 |
ES2435092B1 (es) | 2012-06-14 | 2014-09-09 | Aglaris Cell S.L. | Método y sistema de cultivo celular |
DK2961531T3 (da) * | 2013-03-01 | 2022-03-14 | Genea Ip Holdings Pty Ltd | Anordning, fremgangsmåde og system til overvågning af udvikling af dyrkede prøver |
WO2015023658A2 (fr) | 2013-08-12 | 2015-02-19 | Invivosciences Inc. | Système et procédé automatisés de culture cellulaire |
CA2961223C (fr) * | 2013-12-12 | 2019-04-30 | Yamaha Hatsudoki Kabushiki Kaisha | Un appareil mobile servant a deplacer un sujet au moyen de pointes |
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JP6619544B2 (ja) * | 2014-03-19 | 2019-12-11 | 株式会社日立ハイテクノロジーズ | 検査装置 |
US11041871B2 (en) * | 2014-04-16 | 2021-06-22 | Bd Kiestra B.V. | System and method for incubation and reading of biological cultures |
DE102014213348B4 (de) | 2014-07-09 | 2024-07-04 | Carl Zeiss Microscopy Gmbh | Durchlichtmikroskop und Verfahren zur Durchlichtmikroskopie |
DE102014220306B3 (de) * | 2014-10-07 | 2015-09-03 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Automatisches Verfahren zur Beobachtung von Zellkulturwachstum |
US20180072980A1 (en) * | 2015-03-18 | 2018-03-15 | Rohto Pharmaceutical Co., Ltd. | Apparatus to produce cultured cell products and method for producing cultured cell products |
CN107406815A (zh) | 2015-04-23 | 2017-11-28 | 株式会社日立高新技术 | 感受性测量装置及检查装置 |
KR101767336B1 (ko) * | 2015-07-09 | 2017-08-10 | 사회복지법인 삼성생명공익재단 | 자동 세포 배양기 및 그 배양기의 동작 방법 |
US10351812B2 (en) | 2015-08-28 | 2019-07-16 | Axion Biosystems, Inc. | Device and system for creating and maintaining a localized environment for a cell culture plate |
CN106244456B (zh) * | 2016-08-29 | 2019-05-10 | 杭州键一生物科技有限公司 | 全自动智能培养箱及其控制方法 |
KR102444077B1 (ko) | 2017-11-29 | 2022-09-16 | 한국전자통신연구원 | 세포 노출 시스템 |
CN110643577A (zh) * | 2018-06-26 | 2020-01-03 | 深圳市北科生物科技有限公司 | 基于机械臂的全自动细胞培养方法及其系统 |
CN108707551B (zh) * | 2018-06-27 | 2022-12-20 | 深圳市深研生物科技有限公司 | 一种细胞观察方法 |
LU100885B1 (de) * | 2018-07-25 | 2020-01-27 | Cytena Gmbh | Vorrichtung mit wenigstens einem Behältnis |
KR20200032830A (ko) * | 2018-09-19 | 2020-03-27 | 메디칸(주) | 자가 줄기세포의 자가 배양 방법 및 장치 |
CN109294909A (zh) * | 2018-09-30 | 2019-02-01 | 镇江华智睿安物联科技有限公司 | 一种细胞观察培养箱 |
KR102156091B1 (ko) * | 2018-11-27 | 2020-09-15 | 김철 | 인장자극 및 실시간 관찰이 가능한 배양체 인큐베이터 시스템 |
KR102330693B1 (ko) * | 2019-11-26 | 2021-11-24 | (주)인포바이오테크 | 세포 배양기 |
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DE102019134003A1 (de) * | 2019-12-11 | 2021-06-17 | Aixinno Limited | Verfahren und Vorrichtung zum Kultivieren biologischer Zellen |
CN111004706B (zh) * | 2019-12-23 | 2023-06-16 | 长春长光辰英生物科学仪器有限公司 | 一种用于微小尺寸目标分选仪器中的高通量接收系统 |
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WO2024138094A1 (fr) * | 2022-12-22 | 2024-06-27 | Eikon Therapeutics, Inc. | Systèmes de balayage de ligne oblique et procédés de suivi de molécule unique à haut débit dans des cellules vivantes |
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WO2004090093A1 (fr) * | 2003-04-09 | 2004-10-21 | Olympus Corporation | Dispositif de traitement de culture et dispositif de traitement de culture automatique |
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EP1598415A1 (fr) * | 2004-05-20 | 2005-11-23 | The Automation Partnership (Cambridge) Limited | Culture cellulaire intelligent |
DE102005023855A1 (de) * | 2004-05-26 | 2006-01-26 | Olympus Corporation | Kulturmikroskop und Computerprogramm zur Steuerung des Kulturmikroskops |
JP4599937B2 (ja) * | 2004-08-18 | 2010-12-15 | 株式会社ニコン | 自動培養装置、および自動培養システム |
JP2008533989A (ja) * | 2005-03-22 | 2008-08-28 | アイアールエム・リミテッド・ライアビリティ・カンパニー | 化合物をプロファイル解析するデバイス、システムおよび関連方法 |
JP2007024576A (ja) * | 2005-07-13 | 2007-02-01 | Fujifilm Holdings Corp | 細胞重層培養物における毒性試験装置 |
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2010
- 2010-04-22 EP EP10721643A patent/EP2384363A2/fr not_active Withdrawn
- 2010-04-22 US US13/257,148 patent/US20120034596A1/en not_active Abandoned
- 2010-04-22 KR KR1020117023154A patent/KR20110133589A/ko not_active Application Discontinuation
- 2010-04-22 JP JP2012506336A patent/JP2012524527A/ja active Pending
- 2010-04-22 WO PCT/DE2010/000454 patent/WO2010121601A2/fr active Application Filing
Non-Patent Citations (1)
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See references of WO2010121601A2 * |
Also Published As
Publication number | Publication date |
---|---|
KR20110133589A (ko) | 2011-12-13 |
WO2010121601A2 (fr) | 2010-10-28 |
WO2010121601A4 (fr) | 2011-06-03 |
WO2010121601A3 (fr) | 2011-04-14 |
US20120034596A1 (en) | 2012-02-09 |
JP2012524527A (ja) | 2012-10-18 |
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