Incubators, systems and methods for monitored cell growth - Patents.com

Abstract

The present invention relates to an incubator, system, and method for monitoring cell growth in a cell culture by detecting cell monitoring data within the incubator, the incubator having a data storage device (4a) and a data processing device (4b), the data processing device (4b) configured to detect at least one incubator chamber value and at least one cell growth value in the form of cell monitoring data, and to store the cell monitoring data within the data storage device.

Description

[Technical field]

[0001] The present invention relates to an incubator for monitored biological cell growth.The present invention further relates to a system and method for monitored biological cell growth. [Background technology]

[0002] Such incubators allow cells in cell culture to be kept under controlled ambient conditions in biological and medical laboratories, thus allowing the growth of living cells in vitro (in a test tube). For this, the temperature and gas composition or air humidity of the atmosphere inside the incubator chamber, which is isolated from the surroundings, are kept at desired values ​​by the incubator's instrumental devices. Eukaryotic cells grow in CO 2 An incubator is required. The atmosphere must be CO 2 Content and O 2 The optimum temperature is often 37°C.

[0003] Cells are required for a wide variety of applications in biology, medicine and pharmacy. What is important here is that the cells are provided in the desired state, i.e. in a reproducible form. Immortalized cell lines provide particularly suitable prerequisites for this, since they allow genetically identical cell types and an almost unlimited number of cell division cycles, and they also allow freezing (and thawing) in temperature-regulated long-term storage at -196°C.

[0004] Cell growth is particularly crucially dependent on the ambient conditions in the incubator. On the one hand, the incubator chamber is therefore regularly handled by cleaning and disinfection procedures. On the other hand, incubators have particularly high-value electronic and sensor systems. The sensors are usually calibrated regularly. In practice, however, cell growth does not show the expected results, even though the necessary maintenance procedures are supposedly exactly observed. This even applies to immortalized cell lines.

[0005] To obtain information about the growth process, the cell culture or its cells are subjected to visual and morphological examinations as well as cell counts outside the incubator. Such procedures result in a snapshot, which can serve to determine the cell growth up to this point. However, such procedures interrupt the cell growth and disturb it by movement of the cell culture medium and by at least temporary exposure in the laboratory space atmosphere. It is doubtful that the cells thus examined can be reliably further developed. Moreover, removing the cell culture vessel from the incubator will disturb other cell cultures in the incubator due to the disturbance of the incubator atmosphere when the incubator door is opened.

[0006] Auxiliary devices for the observation of cell cultures are known. These auxiliary devices are arranged in the incubator and can provide information on the determined cell culture growth on an external computer by means of these auxiliary devices. In this case, the auxiliary devices do not have to be removed from the incubator chamber. In this way, the user can obtain information from the computer on the state of the cell culture growth, for example by image transmission and / or image evaluation. What seems to be less satisfactory about such solutions is the high overall equipment effort of such systems, especially with regard to the procurement of the auxiliary devices and the incubator, their maintenance, and also the high effort required during operation. Since the auxiliary devices are furthermore operated independently of the incubator, careless adjustment of the incubator or the auxiliary devices by the user can lead to malfunctions or damage to the devices. For example, temperature-sensitive devices can be left in the incubator chamber during high-temperature disinfection of the incubator, or temperature-insensitive devices can be removed unnecessarily. It is also possible that temporarily unused auxiliary devices are left inserted in the incubator chamber, disturbing the climate. Summary of the Invention [Problem to be solved by the invention]

[0007] Therefore, the problem underlying the present invention is to provide cells in a desired state in a better reproducible and efficient manner. [Means for solving the problem]

[0008] The present invention achieves this object by an incubator according to claim 1, a data exchange system according to claim 10, a system according to claim 11 and a method according to claim 12. Advantageous configurations are in particular the subject of the dependent claims. Effect of the Invention

[0009] An incubator for monitored cell culture growth according to the present invention comprises an incubator chamber for accommodating at least one cell culture vessel containing a growing cell culture, a sensor device for measuring at least one chamber parameter characterizing a physical state of the incubator chamber in the form of at least one first measurement value, at least one measurement device for measuring at least one growth parameter characterizing the growth of cells of the cell culture in the form of at least one second measurement value, a data storage device, and a data processing device configured to detect the at least one first measurement value and the at least one second measurement value in the form of cell monitoring data and to store the cell monitoring data in the data storage device.

[0010] Unlike known incubators, the incubator of the present invention introduces an instrument format that serves as a clearinghouse. This instrument format collects information about the growth of cells in the individual incubators and thus obtains reference data that allows a standardized approach for cell culture in the incubator. The incubator's high-value and precisely calibrated sensor system provides the basis for collecting reliable data sets that characterize the cell growth in this incubator under the incubator's atmospheric conditions, in particular CO2, O2, relative air humidity, and / or the number or duration of door openings. Since the incubator's internal parameters, in particular the chamber parameters, are collected together with the growth parameters measured by the measuring device, it is possible to determine the resulting correlations between the parameter values ​​and their changes. Thus, cell monitoring data is obtained in the incubator. The cell monitoring data can be used as reference data for evaluating the development of cell cultures to be grown in the incubator in the future. By simultaneously detecting the incubator's environmental conditions as first measured values ​​and the growth parameters as second measured values ​​and storing both measured values, this information is present centrally in just one device. In the function of the incubator as an information center, such an incubator may be connected to a network, and via such a network the detected data can be transmitted and deposited in a data bank that is publicly accessible or accessible only to a defined user circle. The provision of such data makes it possible for the first time to collect, provide and also document information on cell growth under detected environmental conditions for any user. It is possible to associate such cell monitoring data with the detected ambient condition data of the incubator. Standardization of cell culture is thus possible. It is also significantly easier to transfer the detected cell data and ambient condition data between work groups, which is also global.In this way, it is possible to support collaboration between users based on available data and feedbackable results, which allows cell culture to be reproducible. Especially when growth results are poor, cell culture measurements alone are not sufficient to perform a root cause analysis. For the first time, it is now possible to facilitate root cause analysis, since incubator chamber parameter data, i.e. ambient condition data, are also available and can have an influence during root cause analysis.

[0011] The interior of the closed incubator chamber and the parts provided therein form one physical system. This system can be controlled precisely by the incubator in optimal cases. For this, precisely working and preferably calibrable sensor devices of the incubator are particularly useful. Such a closed system defines the living environment of the cell culture. The detection of the physical state of such a closed system thereby allows the precise detection of the living or growing state of the cell culture. Such an arrangement provides ideal prerequisites for using the incubator as a data collection center. In particular, the advantage of such an arrangement is that there is precise information about all procedures and actions of the incubator chamber, which are controlled, i.e. in particular initiated, by the incubator or its electronic control device itself.

[0012] Particularly important actions that are controlled by the incubator or at least preferably detected by a sensor of the incubator are the opening and / or closing of the incubator door, in particular the chamber door of the incubator chamber. The sensor device is preferably configured to detect the opening and / or closing of the incubator door as a chamber parameter, since the opening and / or closing of the incubator door is a physical state of the incubator chamber. Such chamber parameters are preferably stored in a time-dependent manner in each case. The information "door open" and / or "door closed" can be stored in a time-dependent manner in the form of values ​​of the corresponding incubator door parameters. Experience has shown that the opening of the incubator door and the corresponding atmospheric changes inside the incubator chamber have a significant influence on cell growth, in particular if openings are frequent (which may occur if the incubator is equipped with several cell cultures). It is therefore particularly useful to correlate the incubator door parameters with the growth parameters, in particular if both are stored in a time-dependent manner. The chamber parameters are in particular related to the atmospheric conditions present in the incubator chamber, e.g. CO 2 , O 2 , N 2 , relative air humidity, and / or the number or duration of door openings.

[0013] The operations controlled by the incubator itself further include all temperature regulation steps affecting the physical condition "temperature of the incubator atmosphere", in particular the automatic disinfection steps with high temperature phases from about 100° C. to 120° C., or even up to 180° C. or 200° C. These steps are carried out in an empty incubator chamber. The incubator or its control device is preferably configured to store in the cell monitoring data the temperature set as the target temperature of the temperature regulation circuit at a given time, or the temperature value detected as a result of the temperature regulation.

[0014] The operations controlled by the incubator itself can furthermore include gas exchange operations, during which parts of the incubator atmosphere are exchanged on the basis of a volumetric flow with a given volume per time, in order to adjust the desired gas composition of the incubator atmosphere, in particular as part of a regulation operation, in case the gas composition has changed in an undesirable way, in particular after opening of the incubator door. The corresponding measured physical state is in this case the relative gas concentration or the relative air humidity. The incubator or its control device measures the relative gas concentration set as the setpoint value of the temperature regulation circuit at a given time, or the gas values ​​detected as a result of the relative gas concentration, in particular CO 2 and / or O 2 Preferably, the value is configured to be stored in the cell monitoring data. For such gas regulation, an adjustment of air humidity can also be taken into consideration. The adjustment of air humidity is performed by an air humidity sensor of the sensor device, in particular by a sensor for measuring relative air humidity.

[0015] The operations controlled by the incubator itself can further include gas transfer operations, in which parts of the incubator atmosphere are transferred, for example based on a volume flow with a given volume per time and in particular with one or several variable or constant flow directions within the incubator chamber, which in particular leads to a homogenous atmosphere inside the incubator chamber, so that in particular cell culture vessels at different positions can be supplied with the same atmosphere, averaged over time.

[0016] The measuring device is configured to measure at least one growth parameter characterizing the growth of cells of such cell culture. The growth parameter may be the pH value of the cell medium of the cell culture, when the measuring device comprises at least one pH detector, by means of which the pH value of the medium can be measured or evaluated. The pH detector may be non-invasive, for example, because it is based on an optical measurement of the cell culture, in particular a color recognition of the cell medium. The medium is provided with a pH-dependent dye, thereby allowing a visual inspection of the pH value. Such a situation may also be utilized for measurements by optical instruments as described.

[0017] If the measuring device is configured as a cell counting measuring device, the growth parameter can represent the number of cells in the test section of the cell culture vessel. For this purpose, the measuring device preferably has an image acquisition sensor, for example a CMOS sensor. By this sensor, an image or a film of the cells to be counted is acquired. By image, it is preferably meant a data set that contains in particular the values ​​of the light intensity received by the light-sensitive elements of the image sensor. However, within the scope of the present invention, it is not necessary that the image represents an optical image, in particular an image of the cell culture. The image can then be evaluated by software-based image recognition, in particular by particle recognition and particle counting, which is preferably integrated as a component into the incubator or system according to the invention. Furthermore, a light source may be provided as a component of the measuring device. The light beam of the light source preferably captures the cell culture and is in particular directed towards this cell culture. Furthermore, at least one means for influencing the light emitted from the light source and / or the light detected by the sensor may be provided as a component of the measuring device. By means of the optical system, a reflected light microscopic analysis, in particular a phase contrast microscopic analysis or a dark field microscopic analysis can be realized.

[0018] The growth parameter can represent the confluence of the cell layer in the cell culture vessel, i.e. the cell density. For this purpose, the measuring device is preferably configured as a confluence measuring device. For this purpose, the measuring device preferably has an optical sensor and preferably has a light source as a component of the measuring device. The light beam of the light source preferably captures the cell culture and is in particular directed towards this cell culture. Furthermore, at least one means for influencing the light emitted by the light source and / or the light detected by the sensor may be provided as a component of the measuring device. Such means are selected from the group of advantageous means, which comprises lenses, prisms, optical filters, mirror elements, optical fibers. By means of the optical system, reflected light microscopy, in particular phase contrast microscopy or dark field microscopy can be realized. Such a sensor is preferably a spatially resolving sensor, for example a CMOS sensor or a camera. In this way, an image of in particular the cell layer can be acquired by a sensor. Such an image can then be evaluated by software-based image recognition, in particular by edge detection of structures surrounded by edges, and edge counting. These constructs can be interpreted as the adherent cells of the cell layer.

[0019] The measuring device may for this purpose be configured to measure the confluence by performing electrical measurements on the cell layer of the cell culture, in particular by measuring the electrical resistance or impedance of the growing cell layer, in particular by time-resolved measurements. The cell layer forms an electrical capacitance which can be used for its characterization. For this purpose, the cell culture vessel preferably has an electrode, in particular a planar electrode, above which the cell layer is formed. Such an electrode is designed so that it can be electrically connected to a measuring device of the incubator. Such a measuring technique is known in particular under the name impedimetry or ECIS (English: electric cell-substrate impedance sensing).

[0020] Another method for determining the confluence state of a cell layer on a substrate of a cell culture vessel can involve radioactively marking the cells and / or marking them with a cell stain and observing them by reflected light microscopy, in particular phase contrast or dark field microscopy. Fluorescence microscopy for confluence analysis is also possible. In this case, the cells are marked with fluorescently marked proteins / particles and thus visualized.

[0021] The growth parameters may further describe the morphology of the cells of the cell layer. The cell morphology may be characteristic for a certain growth stage of the cells. Non-adherent cells in suspension are mostly formed as spheres, whereas when they adhere to a flat substrate they flatten and form an almost planar shape on the substrate side. The cell morphology may be characteristic for a cell type or cell line and may be distinguished by morphometric measurements. The cell morphology may also describe the apoptotic or necrotic state of the cells, which may be determined by morphometric measurements.

[0022] The measuring device is therefore preferably configured as a morphometric measuring device. For this purpose, the measuring device preferably has an optical sensor and preferably has a light source as a component of the measuring device. The light beam of the light source preferably captures the cell culture and is in particular directed towards this cell culture. Furthermore, at least one means for influencing the light emitted by the light source and / or the light detected by the sensor may be provided as a component of the measuring device. Such means are selected from the group of advantageous means, which comprises lenses, prisms, optical filters, mirror elements, optical fibers. By means of the optical system, reflected light microscopic analysis, in particular phase contrast microscopic analysis or dark field microscopic analysis can be realized. Such a sensor is preferably a spatially resolving sensor, for example a CMOS sensor or a camera. In this way, by means of one sensor, in particular an image of the cell layer can be acquired. Such an image can then be evaluated by software-based image recognition, in particular by edge detection of structures surrounded by edges, and edge counting. These structures can be interpreted as adherent cells of the cell layer.

[0023] The measuring device preferably comprises an analogue-to-digital converter for digitising the at least one second measurement value, i.e. the measurement value of the at least one growth parameter, and providing it as cell monitoring data. The measuring device preferably comprises a (own) data processing device, in particular also called second data processing device, in particular a microprocessor, and a own data storage device, preferably also called second data storage device. The measuring device is preferably arranged to measure the at least one second measurement value independently of the data processing device of the incubator or to control the performance of such measurements on the basis of an own control program (second control program) executed in particular by the second data processing device.

[0024] However, it is also possible and particularly advantageous for the data processing device of the incubator (first data processing device) to control the measurement execution of the at least one second measurement value. This allows for an efficient cell monitoring data detection with low energy consumption. In implementation, it must be noted that the operation of the electrical devices inside the incubator chamber possibly results in waste heat. This waste heat heats the chamber atmosphere to an unacceptable extent. The control device of the incubator may therefore be particularly configured to control the operation of the electrical devices, in particular the at least one measuring device and / or handling device inside the incubator chamber, depending on the temperature of the chamber atmosphere detected by the temperature sensor. The control device of the incubator may be particularly configured to compensate for undesired heating of the chamber atmosphere by controlling the temperature regulation of the chamber atmosphere by the at least one temperature regulation device and the operation of the electrical devices inside the incubator chamber in a mutually dependent manner.

[0025] The detection of the first and second measured values ​​and / or their storage is preferably controlled by a data processing or control device of the incubator and is in particular based on the definitions of a monitoring program, which may be a component part, in particular a subprogram, of a control program of the incubator.

[0026] The data processing device is preferably a constituent part of a control device of the incubator, which controls the functioning of the incubator. The functions of the control device are in particular realized by electronic circuits. The control device may have a microprocessor. The microprocessor may comprise a data processing device. The control device and / or the data processing device are preferably formed to implement a control method, also called control software or control program. The functions of the incubator and / or the control device can be described in method steps. These can be realized as constituent parts of the control program, in particular as subprograms of the control program.

[0027] Within the scope of the present invention, a control device generally comprises or is in particular a data processing device, in particular a computing unit (CPU) and / or a microprocessor for processing data. The data processing device of the control device of the incubator can also advantageously be configured to control the handling process and / or the individual handlings, which are carried out by one or several, in particular any, handling devices of the incubator.

[0028] The data processing device is preferably an apparatus arranged outside the incubator, separate from the incubator. Such an apparatus is also called an external apparatus or external data processing device. The data processing device and the incubator are preferably data-connected and are also preferably components of a network for data exchange. The data processing device and the incubator are in this case in particular components of a system according to the invention for monitoring the growth of cell cultures. Such network components are also called here network devices. At least one measuring device may also be configured as a network device. The network for data exchange is preferably a primarily non-hierarchical network, in particular a network whose participants, i.e. network devices, form at least partially or entirely a peer-to-peer network architecture. In a peer-to-peer network, all participants have equal rights and can both use and provide services. The network for data exchange preferably uses Ethernet technology, preferably an Ethernet network.

[0029] The system, the incubator, and / or the control device, and / or the data processing device, and / or the at least one measuring device may be configured as follows: - detecting cell monitoring data at points in time based on a predefined time plan, which may be established by the incubator and / or may be influenced or established by a user via a user interface device of the incubator, such designations of points in time including absolute date and time designations, which the incubator utilizes by comparing them with clock data which may optionally and preferably be provided to the incubator; - detecting cell monitoring data at defined time intervals, in particular at regular time intervals, such as time intervals dt=10 min to 20 min, which may be determined by the incubator and / or may be influenced or determined by a user via a user interface device of the incubator; Preferably, the following events occur: o the first measurement value measured by the sensor device indicates a defined condition, e.g. an unacceptable deviation from a target temperature (37°C) in the incubator chamber, which may be due to, for example, an open incubator door, or a relative gas concentration in the incubator chamber, e.g. CO 2 and / or O 2 Value and / or N 2 The conditions for unacceptable deviation of values ​​were met and typical CO 2 The event that the value is 5% the occurrence of an error condition of the incubator, related to hardware or software, recognized by the incubator; o via a control device of the incubator or a communication device of the measuring device, a control signal is received which triggers the detection of cell monitoring data, said control signal may in particular be initiated by an external data processing device or may be initiated by a user input, detecting said cell monitoring data in dependence on at least one predetermined event selected from the group consisting of: - a control program executed by a data processing device or by the control device or by the measurement device of the incubator triggers the measurement of the cell monitoring data after an evaluation method employed by the control program evaluates a previously measured second measurement value, and the evaluation program enables the triggering of the measurement of the cell monitoring data based on a fulfilled condition, said condition being one of the following conditions: At least one previously measured second measurement value deviates from at least one reference value or falls outside a predetermined range, at least one progression of two or more previously measured second measured values ​​deviates from at least one reference progression or from a predefined reference range, said reference progression or range being a known reference progression or range which may in particular depend on information about other parameters, in particular the cell type or the cell culture medium used for the cell culture, The condition can be selected from the group of: It is preferable that the cell monitoring data is detected based on at least one of the following configurations:

[0030] The system, the incubator, and / or the control device, and / or the data processing device, and / or the at least one measuring device are preferably configured to detect the cell monitoring data depending on the cell identification data. The cell identification data can be previously input by a user, for example via a user interface device of the incubator. The incubator or the system may comprise an identification device for recognizing the cell culture vessel or the cell culture. In particular, correlation data information may be present in the incubator regarding the correlation consisting of the cell identification data and a pre-prepared marking. The marking may be attached to the cell culture vessel and may be machine-readable via a reading device of the incubator or the system. The marking may be a code, in particular a barcode, a two-dimensional code, or a machine-readable sign or sign sequence.

[0031] By detecting cell monitoring data depending on cell identification data, data collections can be set and stored depending on cell type, particularly cell line. In particular, the growth history of a given cell or cell line sample and subcultures obtained by passaging the sample can be detected. An electronic cell file with such historical growth data can be detected.

[0032] The growth behavior of a cell or cell line type can be tracked independently of the origin of individual cell or cell line samples, which may have been passaged, frozen and thawed again. In this case, preferably furthermore, depending on the individual incubator used, the production lot of the incubator, the incubator type or other information, cell monitoring data of such a cell or cell line type is repeatedly detected from several individual cell or cell line samples. Such detection can be performed in the system according to the invention, in particular via locally or globally distributed incubators, or on a national and worldwide scale. Thus, an electronic cell file can be prepared from such historical growth forms for a cell or cell line type. From this, useful reference data and information correlations can be derived, in particular reference trends and reference ranges can be determined. These reference trends and reference ranges can be used as reference data by the incubator or the system according to the invention.

[0033] The information correlation can include, for example, how a given cell line has a different characteristic growth state since a given number of passages or how the growth progression depends on the number of passages. The information correlation can also include, for example, how the growth progression of a given cell line depends on the number of incubator door openings or the total time the incubator door is open or other statistical information regarding the opening of the incubator door. The information correlation can also include, for example, how the growth progression of a given cell line depends on the number and / or type of exchange of the nutrient medium of the cell culture. The information correlation can also include, for example, how the type of cell culture vessel in which the cells are grown influences the growth progression. For this purpose, the incubator can obtain information about the type of cell culture vessel used or the individual identification number of the cell culture vessel by the user by detecting the cell culture vessel data at the user interface. The order number and the lot number can also be detected here together. This can in particular back-track whether this type of cell culture vessel or the growth surface of such a production batch has functioned satisfactorily.

[0034] In particular, the incubator or system according to the invention allows at least one control parameter to be determined depending on such reference data, the control parameter having an effect on a control method of the incubator, the effect being that the control method outputs information to a user via a user interface device depending on the control parameter, the information being at what point in time the cell culture vessel must be removed from the incubator in order for certain growth parameters desired by the user to be present, e.g. cell adhesion, cell number in the vessel, cell density, morphology.

[0035] The system, the incubator, and / or the control device, and / or the data processing device, and / or the at least one measuring device are preferably configured to use the cell monitoring data to form an electronic documentation file, in which the growth of individual cell samples in a cell culture vessel or the growth of several cell cultures in a cell culture vessel is protocolized and documented. Such documentation file is then stored in a data storage device. Since the cell monitoring data allows for reverse inference to ambient conditions, on the one hand, compliance with a given standard protocol for the cultivation of cells can be proven. On the other hand, deviations from such a standard protocol can be determined later and / or information correlations can be determined. By the detection of such data, the quality of cell-based laboratory work or medical, biological and pharmaceutical methods can be significantly improved and made more reliable. The reproducibility of cell-based laboratory work can be increased, and early recognition of deviations from reference characteristics gives the user the possibility of correction or early repetition of tests. The documentation file can be provided from the control device to the user or to an external data processing device via data exchange. In particularly critical applications, for example those having legal relevance or where high value cells are cultured, such documentation is particularly meaningful.

[0036] The invention serves in particular to achieve a standardization of the growth course of cells in a cell culture, so that a user reaches a growth result desired by the user, in particular a defined cell adhesion, for example after thawing of the cells, the number of cells in the cell culture, the cell density and / or the morphology of the cells, each also called growth target. This is achieved in particular by detecting a dependency of the cell growth on a first and / or a second measured value of the cell monitoring data. The cell growth is represented in particular by at least one growth parameter. Detection of the second measured value at predefined times can be used to reach the growth target while using a planning program. The incubator according to the invention serves in particular as a tool for the unification (standardization) of the approach to reach a desired growth parameter in a cell culture. The cell monitoring data forms a database, based on correlations (information correlations) of the cell monitoring data, which can be determined in particular by the first and second measured values, or on causal relationships between the cell monitoring data, which depend in particular on the cell type, in particular on the cell line. For example, it can be determined how the growth parameter depends on the incubator door parameter. The correlations thus determined or the relationships thus determined can be determined to determine a planning program for a cell culture. For example, it can be ascertained that, in particular for a given cell type, cell confluence after cell seeding and / or start of incubation depends on a given number of openings of the incubator door in a defined time from cell seeding and / or start of incubation, and in particular that cell growth is slowed down by such door openings. From such a relationship, it can be inferred, for example, that a user can expect to reach a desired confluence only from a given time point from cell seeding and / or start of incubation, calculated from a correlation known by the incubator.

[0037] Preferably, the incubator and / or the control device and / or the control device and / or the data processing device are configured to perform at least one work step dependent on the cell monitoring data. Such an arrangement advantageously expands the functionality. In an advantageous arrangement, such a work step includes outputting information regarding the cell monitoring data to a user by a user interface device or storing the cell monitoring data in a data storage device.

[0038] Preferably, the control program of the incubator or the system or the external data processing device comprises a planning program, in particular a time planning program. By means of this planning program, a growth plan can be calculated in the form of planning data dependent on the cell monitoring data. Such growth parameters can be calculated by the cell monitoring data for at least one growth parameter, in particular the time course of itself. It is also possible to calculate a time point or time section, i.e. a time point or time section / time point at which / after which the growth parameter can fulfill a defined condition, for example a defined value. Such growth parameters can in particular be cell adhesion (e.g. the number of cells in the cell culture vessel that are adhered to the substrate of the cell culture vessel), the number of cells present in the cell culture vessel after cell division, cell density (the number of cells present in the cell culture vessel after cell division per substrate area), doubling time, or cell morphology (e.g. statistical information on cells present in the cell culture vessel having a given morphological characteristic, for example the substrate area occupied by one cell, the shape contour, for example spherical similarity, the height of the vertical separation relative to the substrate, etc., in particular such morphological characteristics that can be absolutely determined via image acquisition or image evaluation, respectively). The growth parameters may further comprise the pH value of the cell nutrient medium, determined for example via optical absorption measurement of the cell nutrient medium.

[0039] In particular, the planning program can also calculate when an electronic access blocking device of the incubator automatically blocks a user from accessing at least one function of the incubator. The incubator door can have, in particular, an electronically controllable lock as an access blocking device. This lock prevents the incubator door from being opened. The access blocking device can in particular be a component part of the control program. This control program can activate / deactivate software-controlled functions of the incubator. In this way, the growth of the cell culture in the incubator can be protected against atmospheric disturbances during sensitive phases.

[0040] Preferably, the control program of the incubator or system or the external data processing device includes at least one predictive algorithm to calculate at least one growth parameter, in particular its own time course, according to the cell monitoring data, which predictive algorithm preferably represents a known baseline course of the growth parameter that changes depending on the cell monitoring data.

[0041] Prior to the work steps that are carried out depending on the cell monitoring data, as part of the evaluation method, the cell monitoring data can be compared with reference data, which can have been previously determined by the same incubator or can have been transferred to the incubator to be evaluated by means of a data connection.

[0042] Work steps performed depending on the cell monitoring data may output information, in particular regarding planning data, to a user via a user interface device or allow data, in particular planning data, to be transmitted to an external data processing device via a communication device of the incubator.

[0043] The work steps performed in dependence on the cell monitoring data allow for control of at least one control parameter related to the regulation or adjustment of an atmosphere in the incubator chamber in dependence on the cell monitoring data.The work steps performed in dependence on the cell monitoring data allow for control of a process by a processing device in dependence on the cell monitoring data.

[0044] The control method is preferably configured to operate the incubator in dependence on the cell monitoring data to achieve defined growth targets.

[0045] An incubator is a laboratory incubator, and thus an apparatus, by means of which controlled climatic conditions for various biological developmental and growth processes can be created and maintained. Incubators serve in particular to create and maintain a microclimate in which the gas humidity conditions, and / or air humidity conditions, and / or temperature conditions in the incubator chamber are controlled. Such handling can be time-dependent. Laboratory incubators, in particular handling devices of laboratory incubators, can in particular be timers, in particular timer switches, heating / cooling devices, and preferably regulating devices for the regulation of the exchange gas supplied to the incubator chamber, in particular the gas content, i.e. CO 2 and / or O 2 and / or N 2The incubator, in particular the handling device of the incubator, has in particular an incubator chamber and preferably also a regulating device with at least one regulating circuit. The regulating circuit is associated with at least one heating / cooling device as regulating member and at least one temperature measuring device as measuring member. The regulating circuit allows the temperature in the incubator to be regulated. In some embodiments, the air humidity can also be regulated. The air humidity can be regulated via evaporation by heating or cooling a water-filled trough in the incubator chamber. CO 2 The incubator is particularly useful for culturing animal or human cells. The incubator may comprise a redirecting device for redirecting the at least one cell culture vessel and / or a shaking device for shaking or moving the at least one cell culture vessel.

[0046] The control device can be configured such that program parameters or control parameters of the incubator are automatically selected depending on the cell monitoring data. The handling of the at least one cell culture in the at least one cell culture vessel, controlled by the control parameters, corresponds to the climatic handling, in particular to which this at least one cell culture is subjected, in an incubator. Possible parameters, in particular program parameters, in particular user parameters, which are used to influence the climatic handling, are in particular the temperature of the incubator space in which the at least one sample is incubated, the O2 concentration in the incubation inner space, the temperature of ... 2 and / or CO 2 and / or N 2the relative gas concentrations in the incubation interior space, the air humidity in the incubation interior space, and / or at least one process parameter that influences or defines the course, in particular the sequence, of an incubation handling program consisting of several steps.

[0047] The sensor device in particular comprises at least one temperature sensor, preferably a number of temperature sensors. The temperature sensor may for example be a Pt100 or Pt1000 temperature sensor. The sensor device preferably comprises a sensor for determining the relative concentration, in particular a CO 2 and / or O 2 and / or N 2 The sensor device preferably comprises a sensor for determining the content of. The sensor device preferably comprises a sensor for determining the relative air humidity.

[0048] The incubator chamber has a chamber wall and at least one opening. Through this opening, the cell culture vessel can be positioned in and removed from the interior of the incubator chamber. Such a chamber opening can be closed by a closure element movably connected to the incubator chamber, in particular an incubator door movably assembled to the incubator chamber by a hinge, in particular one or several chamber doors. In the closed position of the chamber opening, the interior of the incubator chamber is preferably isolated from the surroundings, such that the desired atmosphere controlled by the incubator is adjustable, in particular regulatable. In the open position of the chamber opening, gas can be exchanged between the surroundings of the incubator and the interior of the incubator chamber via such an opening. The chamber opening is typically located in the front wall of the incubator chamber.

[0049] The incubator chamber preferably has several walls. These walls may in particular be integrally and in particular be connected to one another without edges. These walls are preferably formed substantially planar, but may also have a curved shape in whole or in part. The incubator chamber is preferably formed in the shape of a rectangular parallelepiped, but may also have other shapes, for example as a sphere, an ellipse, a polyhedron. The walls are made of a material with low corrosion resistance, in particular stainless steel, copper, brass, or plastic, in particular composite plastic. This makes it easier to clean / disinfect the inside of the chamber. Independently of the openings serving for loading / unloading the cell culture vessels, the incubator chamber may have ports for cable connections from the inside of the incubator chamber to its outside or to the periphery of the incubator.

[0050] An incubator may have only one incubator chamber, but also several incubator chambers. The atmosphere (temperature, relative gas concentrations, air humidity) of these incubator chambers may in particular be adjustable individually or collectively. The typical size of the inside of one incubator chamber is 50-400 liters.

[0051] The incubator chamber can have one or several shelf inserts or a holding frame for holding the insertable devices. Alternatively or additionally, at least one of the inner walls of the incubator chamber can be configured to hold one or several shelf inserts or insertable devices. For this purpose, a holding structure integrated into the wall can be provided, in particular one or several projections, grooves or webs. The shelf insert increases the footprint in the incubator chamber. The insertable device can be configured as a module, which allows the automatic execution of work steps therein, preferably even when the incubator door is closed. The holding frame is also preferably made of a non-corrosive material, preferably stainless steel. The holding frame is preferably configured as an upright object. In this case, the holding frame has at least one socket section, which is located on the bottom wall of the incubator chamber. However, the socket section can also be supported on the side wall of the incubator chamber and / or suspended on the ceiling wall of the incubator chamber.

[0052] The incubator may have a housing that partially or completely surrounds the incubator chamber, and may be substantially rectangular in shape, in particular so that the incubators can be stacked.

[0053] Advantageously, the incubator comprises a handling device for handling at least one cell culture vessel. The term "handling" means that the cell culture or the cell culture vessel is moved and / or transported and / or investigated and / or changed, in particular physically, chemically, biochemically or in another way.

[0054] The handling device may be a motion device. By means of the motion device, the cell culture is kept in motion in the at least one cell culture vessel via a motion program, which is preferably controlled by a control program. The motion device may be a shaking device or a swiveling device. The motion device preferably has a support device, in particular a plate, on which one or several cell culture vessels are placed and / or fixed. The motion device preferably has a drive device, in particular in the case of a shaking device, for example an oscillator drive, by means of which the desired motion program is executed. The configuration of the motion program can be dependent on the growth program state of the cells of the cell culture and can be dependent on the cell type, in particular the cell line. The handling, in particular the configuration and / or control of the motion program can be dependent on cell monitoring data. A handling device may be a swiveling device. By means of the swiveling device, the at least one cell culture vessel is swiveled. The components of the swiveling device correspond to the components of the shaking device, but are configured for swiveling movement.

[0055] The handling device may be a transport device. By means of the transport device, at least one cell culture vessel is adapted to be transported in the incubator chamber. The transport device may be a lifting device having a support device. On the support device, the at least one cell culture vessel can be positioned. The lifting device preferably comprises a movement mechanism and / or an electrically controllable drive mechanism for driving the movement mechanism. The transport device may further be a movable and electrically controllable gripping arm for gripping and holding the at least one cell culture vessel. The transport device may comprise a conveyor belt for moving the at least one cell culture vessel positioned thereon. By means of the transport device, the at least one cell culture vessel in the incubator chamber can be moved to and away from a processing position, in particular of a processing station in the incubator chamber. The control device may be configured to control the transport device depending on the cell monitoring data.

[0056] The processing station comprises at least one measuring device so that at least one growth parameter characterizing the cell growth of such cell cultures can be measured. If at least one cell culture vessel is movable in the incubator by a transport device, the cell cultures of several cell culture vessels can be measured in succession by only one or a few measuring devices. However, by providing several or multiple measuring devices, the growth of several cell cultures can also be observed in parallel.

[0057] The measuring device may be fixable to the transport device for this purpose. The measuring device may be fixable or fixed to the positioning mechanism. The positioning mechanism allows the measuring device to be moved and positioned in the incubator chamber. The positioning mechanism may comprise a movable robot arm and may preferably be electrically controlled, in particular by a control program of the control device. In this way, the cell growth of several cell culture vessels can be measured in succession by one or a few measuring devices. The positioning mechanism may be formed as a component that can be inserted into the incubator chamber. The energy supply of such a component can be carried out via a cable connection to the incubator, preferably via a wall opening, e.g. a port, or via such a cable connection to an external voltage source. The control device may be configured to control the positioning mechanism depending on the cell monitoring data.

[0058] The handling device can also be understood as a temperature regulation device for the incubator chamber. The temperature regulation device regulates the atmosphere inside the incubator chamber to a desired value, in particular to 37° C. The concept of temperature regulation relates to increasing and decreasing the temperature of the atmosphere by heating and cooling. Preferably, the temperature inside is regulated via a temperature change in the incubator walls. Temperature sensors of the corresponding temperature regulation device are located at at least one position inside the incubator and / or distributed outside the incubator chamber, in particular on one wall of the incubator chamber.

[0059] The incubator preferably comprises a user interface device, via which a user can input data to a data processing device or a control device and / or output data to the user via the user interface device. The incubator or such a user interface device is configured such that a user can input at least one operating parameter for operating at least one measuring device into such a user interface device or obtain information from the user interface device. In this way, only one user interface device can be used by the user to influence or control the incubator and the at least one measuring device or to obtain information from them. In particular, the measuring device may be configured to present cell monitoring data to the user in response to a user inquiry made by the user interface device of the incubator, in particular to present the confluence, the cell count and / or statistical information derived from the cell monitoring data and / or an optical image of at least one cell culture.

[0060] The device-controlled handling of the incubator is preferably program-controlled handling, i.e. handling controlled by a program. Program-controlled handling of the specimen means that the handling operations are mainly performed by processing a plurality or a large number of program steps. Preferably, the program-controlled handling is performed by using at least one program parameter, in particular at least one program parameter selected by the user. The parameters selected by the user are also called user parameters. The program-controlled handling is preferably performed by a digital data processing device, in particular being a component part of the control device. The data processing device can have at least one processor, i.e. a CPU, and / or at least one microprocessor. The program-controlled handling is preferably controlled and / or performed according to the specified values ​​of a program, in particular a control program. In particular, in the case of program-controlled handling, little user activity is required, at least after the user has detected the required program parameters.

[0061] By program parameters is meant variables which within a program or subprogram can be adjusted in a predetermined manner so as to be effective for at least one execution (run) of the program or subprogram. The program parameters are for example determined by a user and control the program or subprogram and result in a data output depending on such program parameters. In particular, the program parameters influence and / or control the control means of the apparatus and / or the data output by the program control the control means of the apparatus, in particular the control means of handling by at least one handling device.

[0062] A program is understood in particular to mean a computer program. A program is a sequence of instructions, in particular statements and instructions, which enable a digital data processing device to perform and / or solve certain functions, tasks or problems. A program is usually present as software. The software is used together with a data processing device. The program may in particular be present as firmware, in the present case in particular as firmware of a control device of an incubator or system. A program is usually present on a data carrier as an executable program file, often in so-called machine code. The program file is loaded into the working memory of the computer of the data processing device for execution. A program is processed and thus executed by the processor of the computer as a sequence of machine commands, i.e. processor commands. A "computer program" also in particular means a source text of a program, from which executable code can result in the control sequence of a laboratory apparatus.

[0063] The user interface devices may be components or modules of the incubator. Each user interface device preferably comprises a control device for the user interface device, a communication device for forming a data connection with a laboratory apparatus, in particular an incubator, via its own interface device, an input device for detecting user input from a user, an output device for outputting information to a user, in particular a display device and / or display, in particular a touch-sensitive display. The control device of the user interface device is preferably arranged to exchange data with the control device of the incubator via the data connection.

[0064] The cell culture vessel is in particular made of plastic, in particular PE or PS, and has in particular a planar floor plate. The floor plate forms the growth surface. The growth surface can have a surface treatment means for promoting cell adhesion. The cell culture vessel can be closable or can be equipped with a PE cap or a gas exchange cap, in particular a lid optionally including a filter. The cell culture vessel is in particular stackable. In particular Eppendorf-type cell culture flasks are suitable.

[0065] The invention particularly relates to a data exchange system, comprising at least one incubator according to the invention and at least one external data processing device, which are arranged for data exchange via a data connection, and in particular for exchanging cell monitoring data. Such a data exchange system allows cell monitoring data to be collected by a plurality or a large number of incubators according to the invention, in particular by effectively forming a data collection, which can in particular be collected centrally by an external data processing device. The external data processing device may be arranged to determine, from the large number of collected cell monitoring data, by at least one statistical method, a reference data for the growth of a cell type or cell line in dependence on the cell monitoring data, in particular for a predetermined growth target of such a cell type or cell line, a dependence on the predetermined first and second measured values ​​or cell monitoring data.

[0066] The invention further relates to a system for monitored cell culture growth, comprising at least one incubator, said incubator comprising at least an incubator chamber for accommodating at least one cell culture vessel containing a growing cell culture, a sensor device for measuring at least one chamber parameter characterizing a physical state of said incubator chamber in the form of at least one first measurement value, and at least one measuring device for measuring at least one growth parameter characterizing a growth of cells of said cell culture in the form of at least one second measurement value, said system further comprising: a data storage device, and a data processing device configured to detect said at least one first measurement value and said at least one second measurement value in the form of cell monitoring data and to store said cell monitoring data in said data storage device. This means that the detection and the combination of the first and second measurement values ​​here does not necessarily take place in the incubator, but in a data processing device external to the system, which is not a constituent part of the incubator. In this manner, particularly with several incubators data-connected within laboratory and enterprise laboratory equipment networks, cell monitoring data can be centrally collected and stored by external data processing devices.

[0067] The invention further relates to a method for monitoring the growth of at least one cell culture in an incubator, comprising the steps of: measuring at least one chamber parameter of the incubator chamber of the incubator, said chamber parameter characterizing a physical state of the incubator chamber in the form of at least one first measurement value by at least one sensor device of the incubator; measuring at least one growth parameter characterizing the growth of cells of the cell culture in the form of at least one second measurement value by at least one measuring device of the incubator; detecting said at least one first measurement value and said at least one second measurement value in the form of cell monitoring data by a data processing device of the incubator or of a system; storing said cell monitoring data by a data storage device of the incubator or of the system, said system comprising said incubator. A further optional step of the method consists in performing at least one working step of the incubator in dependence on the cell monitoring data. The method according to the invention is preferably executable by an incubator or a system according to the invention. The method according to the invention is preferably present as a program code, which causes the above-mentioned steps when said program code is executed on a data processing device of an incubator or system according to the invention. The incubator or system according to the invention is preferably configured to carry out the method or program code according to the invention.

[0068] From the description of the incubator according to the invention and its advantageous configurations, further advantageous configurations of the method according to the invention can be deduced.Furthermore, further configuration options of the invention can be taken from the examples in the drawings. [Brief description of the drawings]

[0069] [Figure 1a]FIG. 1a is a perspective view of the front side of an incubator according to the present invention, according to an embodiment. [Figure 1b] FIG. 1b is a perspective view showing the rear of the incubator of FIG. 1a. [Diagram 2] FIG. 2 shows a schematic diagram of an incubator according to the invention according to a further embodiment. [Diagram 3] FIG. 3 is a schematic diagram showing the method of the present invention according to an embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0070] FIG. 1a shows an incubator 1 for monitored cell culture growth, here a CO2 incubator for the growth of eukaryotic cells. The incubator comprises an incubator chamber 2 (see FIG. 2) for accommodating at least one cell culture vessel 9 containing a growing cell culture, and a sensor device 3 for measuring the chamber parameters temperature, relative CO2 gas concentration and relative air humidity. The values ​​of such chamber parameters are periodically read by a control program of a control device 4 of the incubator. The incubator 1 further comprises a measuring device 30 for measuring the growth parameter "confluence of the cell layer in the cell culture vessel" as a second measured value. This is done by illumination and detection of the cell layer prompted by the control device 4 at regular time intervals, or optionally by imaging of the cell layer. The image of the cell layer is evaluated by a data processing device of the control device 4 by software-assisted image analysis methods and the cell density is determined.

[0071] The measuring device 30 here is a network device. The network device is in data connection 6c with the control device or its Ethernet adapter 4c via a plug 6a of the incubator's Ethernet switch 6. The cell culture vessels 9 are arranged on a shelf 20 fixed to the incubator chamber. The incubator chamber 2 is accessible via an incubator door 2a. The opening of the incubator door can be detected by the control device via a sensor 2b.

[0072] The controller 4 comprises a data storage device 4a and a data processing device 4b configured to detect at least one first measurement and at least one second measurement in the form of cell monitoring data and to store the cell monitoring data in the data storage device.

[0073] The incubator 1 thus collects information about the growth of cells in the incubator chamber 2 and thus acquires reference data that allows a standardized approach for cell culture in the incubator. The incubator's highly valuable and precisely calibrated sensor system 3 provides the basis for collecting reliable data sets characterizing the cell growth in such an incubator. Since the incubator internal parameters, in particular the chamber parameters, are collected together with the growth parameters measured by the measuring device, it becomes possible to determine the resulting correlations between the parameter values, and their changes. Thus, cell monitoring data are acquired in the incubator. The cell monitoring data can be used as reference data for assessing the development of cell cultures to be grown in the incubator in the future.

[0074] The user works in a cell culture with eukaryotic cells in a CO2 incubator. The reproducible behavior of such cells in a test system is in the prior art often supported by a subjective impression by morphological examination or by an end point determination (cell count). In addition to this, no automatic documentation of the results of the cells in the incubator is possible in relation to the ambient conditions provided directly in the incubator 1. This classical microscopic analysis of the culture does not cover a complete monitoring of the cells but only forms a snapshot. In addition to this, the snapshot does not provide a quantifiable statement in most cases. Such cell counting in the prior art is a destructive process that is not performed during growth.

[0075] The incubator 1 is further configured to execute, by means of a control program of the control device 4, a planning program which predicts a time-dependent growth course (confluence) from the cell monitoring data and known reference data and displays to the user, via the user interface device 8, information on the achievement of a desired growth goal, here a confluence defined by the user, on the display.

[0076] The cell monitoring data are further optionally transmitted by the incubator or its control device via an Ethernet interface 6a' to an external data processing device 110, which also collects and stores the cell monitoring data, possibly by further incubators (not shown) of the same network 100. This allows the cell monitoring data to be centrally combined and statistically evaluated in the external device to obtain reference data corresponding to the baseline growth of a given cell type or cell line.

[0077] In another embodiment of the invention, the detection of the first measured value together with the second measured value or the combination of them in the form of cell monitoring data is not performed in the data processing device 4b of the incubator, but in the second external data processing device 110. In this way, the measuring device 30 can transmit the second measured value, in particular together with the measurement time stamp, to the external data processing device 110, in particular independently of the incubator 1 or its control device 4, and the control device 4 can transmit the first measured value measured by the sensor device 3, in particular together with the measurement time stamp, to the external data processing device 110. The external data processing device forms the cell monitoring data from the first and second measured values ​​and stores them. The stored cell monitoring data or the reference data acquired therefrom by the data processing device 110 again provide the network equipment of the network, in particular the incubator. In this way, a data exchange system or a system according to the invention is provided, by which the achievement of growth targets can be achieved in a standardized manner.

[0078] A method 200 for monitoring the growth of at least one cell culture in an incubator, shown in FIG. 3, comprises the following steps.

[0079] The method for monitoring the growth of at least one cell culture in an incubator comprises the steps of: Detecting a growth target, e.g., a desired confluence, input by a user via a user interface device (201), particularly in a cell line uniquely defined by the user; Measuring at least one chamber parameter of an incubator chamber of the incubator, the chamber parameter characterizing a physical condition of the incubator chamber in the form of at least one first measurement value by at least one sensor device of the incubator (202a); measuring (202b) at least one growth parameter characterizing the growth of cells in such cell culture in the form of at least one second measurement value by at least one measuring device of the incubator; Detecting (203) at least one first measurement and at least one second measurement in the form of cell monitoring data by a data processing device, and evaluating (204) the cell monitoring data by comparing it to known reference data; Repeat steps 202a, 202b, 203, and 204 until the growth goal is reached or cell growth is terminated by the user; storing (205) the cell monitoring data by a data storage device; Establishing new baseline data using cell monitoring data (206) Provide new baseline data for incubators for future incubation (207) It has steps.

[0080] Monitoring of cells in the incubator 1 and consideration of the movement and memory of the growing cell culture are part of the functionality of the incubator 1 and can be controlled by the incubator. Furthermore, the ambient conditions (first measurement) are automatically correlated with the cell outcome (second measurement) and optionally documented. This allows for a fast and easy standardization of the cell growth behavior.

[0081] The CO2 incubator is equipped with a measuring station 3, which automatically receives information about the cell growth (confluence and optionally cell number). Such information is stored either directly in the incubator 1 or by the system and is therefore present in the incubator in addition to the information about the ambient conditions (first measured value). The incubator information is therefore directly related to the cell data (second measured value).

[0082] Further methods for optimizing the standardization of cell culture with such incubators or systems are preferred.

[0083] After the cell thawing process, the user can determine when all the cells or a defined percentage of the cells are attached onto the surface of the cell container. The user is informed at such point in time, and the deviation from a known baseline is preferably transmitted to the user or stored as data.

[0084] The user obtains information about the amount of cells present in an attached state after seeding or after the thawing process. If the total cell number is entered, the viability can also be determined. The user is informed when the desired cell confluence is reached, for example to manipulate the cells, and can compare such values ​​with already stored values ​​to reach a standardization.

[0085] The user can automatically determine a bandwidth or reference range within which typical measurements for a cell line must lie, given a defined number of samples to be measured.

[0086] With the aid of the incubator, the user can monitor the cell growth. The user can directly control the measuring device 30 with the operating unit 8 of the incubator and can correlate and document the results of the cell growth with the ambient conditions as well as the event log of the incubator. This is preferably done automatically. As the results are stored and present directly in the incubator, the growth curves can be recorded in a standardized state. Once the user specifies the cell type, the actual growth curve is directly compared with the historical data and documented. The user can have deviations automatically evaluated as good or bad by an evaluation algorithm. If there are deviations from the expected results, the user can handle them directly and document them later. As the measuring device 30 is part of the incubator, a one-to-one recording of the ambient conditions of the cell culture is guaranteed.

[0087] In addition, the incubator 1 is optionally integrated in a network 100 and is adapted to transmit the first and second measured values ​​to a data bank of an external processing device. When the incubator or system stores such cell monitoring data, these data are available to all users of the network. When the cell monitoring data are stored, for example, in a cloud, these data can be made accessible to all users of the global network. This allows the combination of cell data and ambient condition data to be automatically transferred between work groups all over the world. This is particularly preferred since collaboration between users is crucial in the academic sector. The more available the cell monitoring data or reference data is and the greater the feedback possibilities of the results, the easier and faster the collaboration in such fields will lead to reliable results. It is known that cell culture is inherently and currently not optimal in terms of method standardization and reproducibility of results. According to the present invention, a global data bank of combined cell data and ambient condition data reliably determined as cell monitoring data allows efficient transfer of protocols and results, since these data are based on reliable incubator data.

Claims

1. An incubator (1) for monitored cell culture growth, comprising: an incubator chamber (2) for accommodating at least one cell culture vessel (9) containing a growing cell culture, said incubator chamber (2) having a chamber wall, at least one incubator door (2a) and at least one chamber opening closable by said at least one incubator door, through which said cell culture vessel (9) can be positioned inside and removed from said incubator chamber; a sensor device (2b; 3) for measuring at least one chamber parameter characterizing a physical state of the incubator chamber in the form of at least one first measurement value; at least one measuring device (30) for measuring at least one growth parameter characterizing the growth of cells of said cell culture in the form of at least one second measurement value; a data storage device (4a) and a data processing device (4b) configured to detect said at least one first measurement value and said at least one second measurement value together in a time-dependent manner in the form of cell monitoring data, and to store and collect said cell monitoring data in said data storage device, thereby providing said stored cell monitoring data as reference data for evaluating the development of a cell culture to be grown in the incubator in the future; It has the sensor device (2b) is configured to detect the opening and / or closing of the incubator door (2a) as a chamber parameter forming the at least one first measurement value, the data processing device is configured to execute a planning program to calculate growth targets for the cell culture dependent on the cell monitoring data; The growth parameters are - the confluence of the cell layer in the cell culture vessel, - the number of cells in the test compartment of the cell culture vessel; - morphology of the cells of said cell layer The incubator is taken from a group of preferred growth parameters including:

2. The incubator and / or the data processing device (4b) of the incubator and / or the control device (4) of the incubator and / or the at least one measuring device (30) are in the following configuration: - detecting cell monitoring data at times based on a pre-determined time plan, which may be established by the incubator and / or may be influenced or established by a user via a user interface device of the incubator; - detecting cell monitoring data at defined time intervals, which may be determined by the incubator and / or may be influenced or determined by a user via a user interface device of the incubator; The incubator of claim 1 , configured to detect the cell monitoring data based on at least one of:

3. The incubator and / or the data processing device (4b) of the incubator and / or the control device (4) of the incubator and / or the at least one measuring device (30) detect the following events: the event that a first measurement value measured by said sensor device satisfies a defined condition, the occurrence of an error condition of the incubator, related to hardware or software, recognized by the incubator; o a control signal is received, via a control device of the incubator or a communication device of the measurement device, which control signal triggers the detection of cell monitoring data, the event being that the control signal may be initiated by an external data processing device or may be initiated by a user input; 3. The incubator of claim 1 or 2, configured to detect the cell monitoring data in dependence on at least one defined event selected from the group consisting of:

4. 4. An incubator as claimed in any one of claims 1 to 3, wherein the incubator and / or the data processing device (4b) of the incubator and / or the control device (4) of the incubator and / or the at least one measuring device (30) are configured such that a control program executed by a data processing device or the control device or the measuring device of the incubator triggers the measurement of the cell monitoring data after an evaluation method adopted by the control program evaluates a previously measured second measurement value.

5. The evaluation program enables triggering of measurement of cell monitoring data based on a condition being met, said condition being: At least one previously measured second measurement value deviates from at least one reference value or falls outside a predetermined range, at least one progression of two or more previously measured second measured values ​​deviates from at least one reference progression or from a predefined reference range, said reference progression or range being a known reference progression or range which may be dependent on other parameters, 5. The incubator of claim 4, wherein the conditions can be selected from the group consisting of:

6. 6. The incubator according to claim 1, wherein the incubator has a user interface device (8) via which both the incubator and the at least one measuring device are controllable by a user.

7. 1. A data exchange system comprising: At least one incubator (1) according to claim 1, At least one external data processing device (110); It has the at least one incubator and the at least one external data processing device are configured to exchange data via a data connection and exchange cell monitoring data; Data exchange system.

8. A method (200) for monitoring the growth of at least one cell culture in an incubator according to any one of claims 1 to 6, comprising: - measuring at least one chamber parameter of the incubator chamber of the incubator, the chamber parameter characterizing a physical condition of the incubator chamber in the form of at least one first measurement value by at least one sensor device of the incubator; Measuring (202b) by at least one measuring device of the incubator at least one growth parameter characterizing the growth of cells of the cell culture in the form of at least one second measurement value; detecting (203) said at least one first measurement and said at least one second measurement in a time-dependent manner in the form of cell monitoring data by a data processing device; storing (205) the cell monitoring data by a data storage device; 16. A method for monitoring the growth of at least one cell culture in an incubator, comprising:

9. The method further comprises: - performing operational steps of said incubator in dependence on said cell monitoring data The method of claim 8, comprising the steps of:

10. The method further comprises: Determining correlations between cell monitoring data and storing information regarding said correlations 10. The method according to claim 8 or 9, comprising the steps of:

11. 10. The method of claim 9, wherein the operating step enables a planning program for calculating growth targets to be executed by a data processing device.

12. 10. The method according to claim 9, wherein the working step enables the growth target time points calculated by the data processing device (4b; 110a) depending on the cell monitoring data to be shown to a user on a user interface device (8) or output in another form.

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