Incubator for cell culture

Abstract

The present invention relates to an incubator equipped with a sensor device for detecting VOC contamination of the gas atmosphere of the inner space of the incubator chamber.

Description

[Technical field]

[0001] The present invention relates to an incubator for the growth of biological cells. The present invention further relates to a system and method for measuring the incubator atmosphere. [Background technology]

[0002] With such incubators, cells in cell cultures are kept under controlled ambient conditions in biological and medical laboratories, thus allowing the in vitro growth of living cells. 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 the desired values ​​by the incubator's equipment. Eukaryotic cells require a CO2-incubator. The atmosphere is formed by air with a defined CO2 and O2 content and a defined air humidity, and the optimal temperature is often 37°C.

[0003] Incubators are ideal growth environments not only for cell cultures, but also for biological contamination. The consequences of biological contamination of cell cultures cause a wide range of problems in biological research, vaccine production, personalized medicine, and regenerative medicine applications. The consequences of biological contamination are thus loss of time and money, and inaccurate or erroneous test results. This also applies, for example, to forensic medicine or regenerative medicine, where the value of individual samples, especially the cells present in a cell culture vessel, is valued significantly higher than, for example, the value of the entire incubator, so that loss of samples due to contamination must be avoided.

[0004] Contamination of the incubator chamber may however have non-biological origins, which may in particular be contamination entering the incubator chamber from the incubator's surroundings. Non-biological contamination may occur, for example, if organic substances are evaporated or liberated from the plastic, in particular from the isolation and / or sealing materials, and enter the incubator chamber as a result of the manufacture of the incubator.

[0005] The scope of functions of prior art incubators often also includes heating the incubator chamber, for example up to 180° C., for the purpose of high-temperature sterilization. During high-temperature sterilization, the incubator chamber must not contain any heat-sensitive objects. Therefore, the incubator chamber must be emptied before high-temperature sterilization, and during this process sensitive samples must be transferred into at least one second incubator. Such additional manipulation of the samples increases the risk of sample loss. Furthermore, there is a risk of introducing, and possibly spreading, contamination possibly occurring in the incubator through the displaced sample container into the at least one second incubator. Carefully performed high-temperature sterilization together with sample transfer means in any case a great deal of effort. Nevertheless, since the sterile state of the incubator chamber is important, it is a standard recommendation of manufacturers to carry out high-temperature sterilization at regular intervals, for example twice a month. In this way, statistically, the risk of sample loss due to contamination is reduced. It is desirable to reduce the effort required of the user to operate the incubator chamber as sterile as possible. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] International Publication No. 97 / 08337 Summary of the Invention [Problem to be solved by the invention]

[0007] The object of the present invention is therefore to provide an incubator, the incubator chamber of which can be operated reliably by a user with as little effort as possible and with minimal contamination. [Means for solving the problem]

[0008] The invention achieves this object by an incubator according to claim 1, a method according to claim 16 and a retrofittable sensor arrangement according to claim 17. Preferred embodiments are especially the subject of the dependent claims.

[0009] An incubator according to the invention for incubating living cell cultures comprises an incubator chamber for receiving an object, in particular a container of a cell culture, in a closable internal space of the incubator chamber operable with a controllable gas atmosphere, a sensor device for detecting an accumulation, in particular contamination, of volatile organic compounds (VOCs) in the gas atmosphere of said internal space, said sensor device having at least one VOC sensor for detecting said VOCs, said at least one VOC sensor having at least one measurement area, said measurement area being arranged in fluid connection with the atmospheric gas of said internal space. Effect of the Invention

[0010] The idea behind the present invention is not to perform high-temperature sterilization of the incubator chamber "blindly" and periodically, but under conditions that allow automatic detection of contamination in the incubator chamber as it occurs. For this purpose, contamination is detected by a contamination detector (VOC sensor, see below) and preferably information about the detected contamination is directly communicated to the user, so that he can initiate high-temperature sterilization. This allows sterilization to be performed when necessary under objective conditions, thus with higher efficiency.

[0011] It is known that certain pollutants are released into the environment through contamination processes, in particular through bacterial and microbial growth. The volatile organic gaseous metabolic products of microorganisms are called MVOCs (English: Microbial Volatile Organic Compounds) and can be used as indicators of microbial growth. In the context of the present invention, in a generalization of the concept of detecting MVOCs, all substances released into the environment or into the incubator atmosphere through chemical processes, in particular contamination processes, are called VOCs (Volatile Organic Compounds).

[0012] In the case of an individual container monitoring function in an incubator, which is known from the prior art DE 10 200 45 54 A1, the incubator has a through opening in the incubator chamber so that gas from such an upper air region of a container arranged in the incubator chamber can be taken by a gas conduit which is led into an upper air region located above the sample volume and transported to a VOC sensor device arranged outside the incubator. In the gas in the upper air region, a container atmosphere is formed in which traces of VOCs from the cell culture contained in the container can accumulate, so that contamination of the cell culture contained in the container can be specifically detected by the measuring device. However, this does not allow detection of contamination formed in the incubator chamber itself, for example on the water tray of the incubator chamber, on the door seal or on the outside of the incubated sample container or other locations which are susceptible to bacterial growth due to moisture formation caused by condensation.

[0013] In the research work that underlies the present invention, a new device was developed in which the gas atmosphere of the inner space of an incubator chamber in which a number of closed cell culture vessels are placed is tested by an incubator-specific VOC sensor device, preferably as a regular active monitoring function during the incubator's operating time. Independent of the source of contamination, the user can thus be warned and sterilization or cleaning of the inner space of the incubator chamber can be initiated. Besides contamination, by measuring the accumulation of VOCs in the incubator atmosphere in general, certain biochemical processes in particular can be found out.

[0014] The sensor device serves to detect contamination of the gas atmosphere of the interior space. The sensor device preferably comprises at least one, preferably exactly one, volatile organic compound (VOC) sensor for detecting at least one VOC. Such a VOC sensor is preferably configured or selected to be sensitive to at least one VOC released by the contamination and to be able to determine whether the concentration of the VOC in the gas atmosphere of the interior space has changed, in particular increased.

[0015] The production of gaseous metabolic products is a fundamental characteristic of microorganisms and all other living organisms. The volatile organic gaseous metabolic products of microorganisms are called MVOCs (English: Microbial Volatile Organic Compounds) and, although their formation depends mainly on the species and the nutrient medium, can be used as indicators of microbial growth. Since cell cultures do not represent microbial organisms, the gaseous metabolic products are called VOCs. For convenience, within the framework of this patent application, both VOCs and MVOCs are called VOCs. This concept also includes compounds, in particular organic compounds, which may evaporate after a certain time from their production, for example from plastic parts. VOCs do not denote CO2 gas (carbon dioxide gas), which is in particular a component of the gas atmosphere of an incubator chamber. Like the VOCs of microorganisms, the VOCs of cell cultures can also be used as indicators of growth, since they provide information about the metabolic and physiological state of the cells.

[0016] The sensor device preferably has a plurality of N VOC sensors, N>1, preferably a number of N=>10 VOC sensors. Preferably, the number of VOC sensors in the sensor device is limited to a maximum number M=2000, 100, 50, 25 or 10. The VOC sensors may all be of different types, which allows a variety of different types of measurements to be obtained and thus a better differentiation of the VOC detection or possible VOC detection or possible VOC classification. Multiple VOC sensors of the same type may be provided. Such an approach may be considered technically "reliable", since it is known in biology that, for example, the human nose uses about 380 different receptor types, and other mammals use a significantly higher number of receptor types.

[0017] Preferably, the sensor device is configured as an electronic nose, in which a plurality or a number of VOC sensors measure the gas atmosphere of the interior space, in particular simultaneously, by simultaneously detecting an accumulation of VOCs from the gas atmosphere, in particular in the measurement area of ​​the VOC sensor. In particular, the electronic nose is suitable or configured for detecting contamination, in particular for recognizing and preferably also quantifying types or classes of contamination, by jointly evaluating the collected measurement signals of a plurality or a number of N VOC sensors, in particular each measurement signal of one of the VOC sensors. The electronic nose is particularly configured to distinguish at least two VOCs present in the gas atmosphere. The electronic nose is particularly suitable for distinguishing between different types or classes of contamination. Furthermore, by means of a plurality of VOC sensors, a more reliable and therefore more sensitive detection of contamination can be achieved than with only one VOC sensor.

[0018] Preferably, the sensor device comprises at least one VOC sensor adapted to detect gaseous metabolic products of microorganisms, in particular bacteria, mycoplasma, fungi, yeasts, etc. Preferably, the sensor device comprises a plurality of VOC sensors with different detection selectivities.

[0019] Preferably, the sensor device comprises at least one VOC sensor configured to detect gaseous metabolic products of biological cells, which allows to obtain information about the growth state of the cell culture, in particular its temporal development.

[0020] Preferably, the sensor device comprises at least one VOC sensor configured to detect gaseous substances escaping from the materials of the incubator components, in particular after a predefined time from the manufacture of the incubator, such gaseous substances including solvents or plasticizers or other substances escaping from plastic components of the incubator.

[0021] Preferably, the sensor device comprises at least one VOC sensor, which is adapted to detect at least one compound belonging to the alcohol family, preferably a plurality of different compounds belonging to the alcohol family. In the research work underlying the present invention, it was determined that alcohol can be detected particularly sensitively in the sense of contamination detection. The reason for this is that the metabolic processes of bacteria, which are particularly relevant for the contamination of incubators, produce alcohol to a certain extent. On the other hand, corresponding commercially available alcohol sensors already have a sensitivity suitable for detecting even the smallest traces of alcohol.

[0022] Preferably, the sensor device comprises at least one VOC sensor, which is configured to detect at least one compound belonging to aromatics, preferably a plurality of different compounds belonging to aromatics. In the research activities underlying the present invention, it was particularly confirmed that aromatics can also be detected particularly sensitively in the sense of contamination detection. The reason for this is that the metabolic processes of bacteria, which are particularly relevant for the contamination of incubators, generate various aromatics. On the other hand, the corresponding commercially available aromatic sensors already have a sensitivity suitable for detecting even the slightest aromatic traces.

[0023] Preferably, the sensor device has at least one VOC sensor, which is configured to detect at least one compound belonging to the alkane family, preferably a plurality of different compounds belonging to the alkane family. In the research work underlying the present invention, it was also determined that alkanes can also be detected particularly sensitively in the sense of contamination detection. The reason for this is also that the metabolic processes of bacteria, which are particularly relevant for the contamination of incubators, generate various alkanes. This also applies in particular to the metabolic processes of cells. On the other hand, corresponding commercially available alkane sensors already have a sensitivity suitable for detecting even the smallest traces of alkanes.

[0024] Particularly preferably, the VOC sensor is configured to detect alcohols, and aromatics and / or alkanes.

[0025] Preferably, the sensor device comprises at least one VOC sensor, which is adapted to detect at least one compound of the compound group, preferably a plurality of different compounds, including {alcohols, aromatics, benzols, alkyl benzols, alkanes, alkenes, alkanes, aldehydes, esters, ketones, pyrazoles, oximes, terpenes, acids, carboxylic acids, heterocyclic amines and indoles}. In the research work underlying the present invention, it was also determined that such substances can also be detected particularly sensitively in the sense of contamination detection. This is also due to the fact that metabolic processes of bacteria, which are particularly relevant for incubator contamination, generate various such substances. This also applies in particular to metabolic processes of cells. On the other hand, corresponding commercially available sensors for various substances already have a sensitivity suitable for detecting even the smallest traces of such substances.

[0026] A VOC sensor is a chemical sensor, particularly for detecting VOCs in a gas atmosphere. Similar or different VOCs detected in the gas atmosphere are detected by the sensor and converted into an electrical signal.

[0027] The VOC sensor may be a conductivity sensor, which in particular measures the conductivity which varies depending on at least one VOC. The VOC sensor is particularly preferably a metal oxide semiconductor (MOX) gas sensor, also called MOX sensor for short. Such chemical sensors have a detection layer, by means of which a chemical interaction can be converted into an electrical signal. These chemical sensors are suitable for continuous measurement operation.

[0028] The function of MOX sensors is based on the fact that depending on the concentration of the target gas, the electrical conductivity of the gas-sensitive metal oxide layer or semiconductor is changed, and thus the presence and amount of the target gas can be determined. Typically, MOX sensors consist of four elements: a gas-sensitive metal oxide layer, an electrode, a heating element, and an isolation layer. The heating element is separated from the gas-sensitive metal oxide layer and the contact electrode by an isolation layer. The gas-sensitive metal oxide layer is heated by the heating element, and oxygen molecules from the environment are adsorbed on the surface of the gas-sensitive metal oxide layer. The adsorbed oxygen molecules capture electrons from the conduction band of the semiconductor, and energy barriers are formed, which block part of the electron flow in the semiconductor, thus worsening the electrical conductivity or increasing the resistance of the gas sensor. As soon as reducing gases (target gases) are present, they react with the bound oxygen molecules. The oxygen molecules are released from the surface of the gas-sensitive metal oxide layer, and the electrical conductivity increases or the resistance decreases.

[0029] The VOC sensor may be a capacitive sensor, detecting a capacitance that changes in response to at least one VOC. The VOC sensor may be an optical sensor, measuring an optical property that changes in response to at least one VOC, such as a changing refractive index, a changing light intensity, or a changing light spectrum, where the wavelength of light used is not limited, and includes in particular infrared wavelengths. The VOC sensor may be a mass-sensitive sensor, measuring a mass that changes in response to at least one VOC, for example by detecting a changing vibration of a vibrating body that interacts with at least one VOC.

[0030] The sensor device is preferably an integral part of the incubator and is in particular arranged in a housing or a housing part of the incubator.

[0031] Preferably, an electronic evaluation device is provided, which preferably includes a data processing device. The evaluation device is configured to record and in particular evaluate at least one measurement signal, in particular a measured value, of the at least one VOC sensor. The evaluation device is preferably a component of the incubator and is in particular arranged in a housing or a housing part of the incubator. The evaluation device can also be a component of the sensor device, in particular if the latter is configured as part of a retrofit system for an incubator that does not yet have such a sensor device.

[0032] In particular, the evaluation device of the incubator preferably comprises a data storage device which is connected for data exchange with the data processing device.

[0033] The evaluation device, in particular a data processing device, is preferably programmable with a program code and is programmed in particular according to such program code to carry out in particular the following steps: Receiving at least one measurement signal, in particular measurement data, of the at least one VOC sensor; in particular receiving a series of measurement signals, in particular forming a temporal measurement course of the at least one VOC sensor, successively in time, in particular over the duration of the measurement time Δt; Comparing at least one measurement signal with at least one reference value; Based on the results of such comparisons, determine whether there are any changes in the VOC concentrations in the gas atmosphere of the interior space, in particular changes characteristic of the contamination of the interior space.

[0034] The at least one reference value may be predefined and may be stored in a data storage device. The at least one reference value may be a starting value obtained from a measurement at the beginning of a measurement time Δt, during which the at least one VOC sensor detects VOC molecules in the gas atmosphere of the interior space. The starting value of the VOC sensor can in particular be determined when the measurement area of ​​the respective VOC sensor is initialized by purging the measurement area with a purge gas, for example nitrogen N2. Such purging is preferably performed until the time course of the measurement signal of the at least one VOC sensor is constant or has a known reference course, for example increases or decreases linearly.

[0035] The evaluation device, in particular a data processing device, is preferably programmed in particular according to such a program code to carry out the following steps: receiving measurement signals, in particular measurement data, of the MOX sensor, in particular measurement signals which are representative of a resistance value, in particular an electrical resistance or a conductivity, of a measurement area; in particular receiving a series of measurement signals, in particular forming a temporal measurement course of the MOX sensor, successively in time, in particular over the duration of a measurement time Δt; preferably by evaluating the measurement signal to derive one or more new measurement signals therefrom; Comparing the measurement signal with at least one reference value; determining, based on the results of such comparison, whether there is a change in the concentration of VOCs in the gas atmosphere of the interior space, in particular a change characteristic for contamination of the interior space;

[0036] The incubator's controller, particularly the data processor, is preferably configured and / or programmed to control the VOC sensor or two or more VOC sensors at a constant voltage.

[0037] Particularly preferably, the incubator control device, in particular the data processing device, is configured and / or programmed to control the one or more VOC sensors with a periodically varying voltage. Such a periodically controlling is an advantageous mode of operation of the sensor device, since the yield of the chemical reaction of the VOC sensor depends on such voltage, or may even depend specifically on the VOC.

[0038] The incubator control device, in particular the data processing device, is preferably configured and / or programmed to control the heating element of the MOX sensor with a cyclically varying voltage, thereby generating a correspondingly cyclically varying temperature in the metal oxide layer. Such an operating mode of the sensor device is also called "temperature cycled operation (TCO)". For this, the heater is controlled here with a voltage UH-Soll having a step-like progression. The voltage provides a number of different values ​​per heating period T. Each of these voltage values ​​is preferably adjusted for a defined portion of the heating period T. The heating period is preferably between 1 second [s] and 60 s, preferably between 5 s and 30 s, preferably between 15 s and 25 s, preferably between 17 s and 23 s, and here is about 20 s. The control results in a measurement signal which varies cyclically during the measurement period T. The heating period can be selected in particular depending on the thermal mass of the VOC sensor.

[0039] In the case of periodic measurement signals, the evaluation is preferably carried out by statistically evaluating one or preferably more periods of the measurement signal to obtain the (evaluated) measurement signal. Preferably, the data processing device is programmed to determine the average course of the measurement period. This may involve superimposing the values ​​of the measurement signal of M measurement periods and then multiplying such an added course of periods by the reciprocal 1 / M. The measurement signal is thus smoothed and the artefactual influence of the measurement is reduced. A median filter for smoothing can also be used. Smoothing can also be carried out by combining several successive measurement signals, in particular the measurement signals of the measurement periods, as an average value, so that the number of measurement signals (then average values) of the measurement curve can be reduced. This is also known as a moving average.

[0040] Preferably, the data processing device is programmed to derive at least one secondary value, referred to as a secondary characteristic, from the signal of a single measurement period or from the average course of one measurement period. The secondary value can be a slope present at a characteristic time point of the measurement period, for example at the time of a change in the voltage value. The characteristic slope can in particular be recorded immediately before or immediately after such a time point, since the slope may not be definable at the time of the change. For further evaluation, the secondary value can be compared as a new measurement signal as described above with at least one reference value corresponding to such a secondary value.

[0041] Preferably, the data processing device is programmed to determine an average value of a number of measurement signals, in particular an average value of a number or substantially all of the measurement signals during one measurement period, which can be compared, as described above, with at least one reference value corresponding to such an average value for further evaluation.

[0042] The incubator, in particular the sensor device, preferably has an electronic control device. The electronic control device may in particular have a second data processing device or the electronic control device uses the data processing device of the sensor device, and the electronic control device is programmed to control at least one valve, by opening the valve, so that the purge gas, in particular N2, flows over the entire measurement area of ​​the at least one VOC sensor. Such a valve may in particular be opened or closed depending on the measurement signal of the at least one VOC sensor.

[0043] The evaluation device, in particular a data processing device, is preferably programmable and is in particular programmed to carry out the following steps: receiving at least one measurement value, in particular measurement data, from at least two, more than two or all of the VOC sensors of the number or plurality of VOC sensors, in particular for each of such at least two VOC sensors: receiving, in particular in parallel in time, successively in time, a series of measured values ​​of at least one VOC sensor, in particular over the duration of a measurement time Δt, said measured values ​​in particular forming a measurement course in time of the at least one VOC sensor; Comparing at least one measurement value of each of the at least two VOC sensors to at least one reference value; determining, based on the results of such comparison, whether there is a change in the concentration of VOCs in the gas atmosphere of the interior space, in particular a change which is characteristic for contamination of the interior space; .

[0044] The at least one reference value can in particular be determined by purging at least one measurement area of ​​the at least one VOC sensor with a purge gas, in particular nitrogen, at a predefined time before or after measuring the gas volume of the incubator atmosphere and performing a reference measurement to detect one or more reference values ​​in the measurement area purged with the purge gas. Comparing the measured value with the reference value, additionally taking into account routinely selectable tolerance values, ensures that VOCs are detected in the gas atmosphere of the incubator chamber.

[0045] As found in the research work underlying the present invention, the accumulation of VOCs, particularly due to bacteria, in the gas atmosphere of the incubator chamber, i.e. contamination, can be easily detected, since bacteria have an exponentially increasing metabolism due to their exponential growth in the corresponding logarithmic phase, which leads to a corresponding exponential increase in the emission of VOCs. In contrast, the emission of VOCs from normally growing cell cultures is very low, insofar as some of these "normal" VOCs enter the gas atmosphere of the incubator chamber, for example through cell culture vessels that are not tightly closed, such as Petri dishes. The metabolism due to bacteria thereby dominates the "odor" of the gas atmosphere of the incubator chamber due to VOCs.

[0046] The evaluation device, in particular a data processing device, is preferably programmable and in particular programmed to carry out the following steps or at least one of the following steps: Optionally, producing result data containing information on the changes in the concentration of VOCs in the gas atmosphere of the interior space, in particular whether there are any changes characteristic of the contamination of the interior space; Optionally, outputting information to a user of the incubator as a function of the result data regarding whether there is a change in the concentration of VOCs in the gas atmosphere of the inner space, in particular a change characteristic of a contamination of the inner space, said outputting of information being in the form of a visual or acoustic signal generated by a suitable output device of the incubator, in particular a display and / or a speaker. Such an output may in particular be configured as a warning signal in order to warn the user of the contamination present; Optionally, storing the result data in a data storage device; Optionally transmitting the result data to an external data processing device, in particular a PC, a smartphone, a tablet computer, in particular by means of a wired or wireless signal connection.

[0047] The VOC sensor is used to detect volatile organic compounds (VOCs), and has a measurement area, which is arranged in fluid connection with the atmosphere gas of the interior space. Preferably, the measurement area of ​​at least one VOC sensor or two or more or all VOC sensors is arranged in an incubator chamber. Preferably, the measurement area of ​​at least one VOC sensor or two or more or all VOC sensors is arranged in at least one or more measurement chambers. The interior space atmosphere of the measurement chamber is preferably fluidly connected with the gas atmosphere of the interior space of the incubator chamber. Such a fluid connection can be formed by connecting the incubator chamber and the measurement chamber by at least one flow path. However, the measurement chamber can also be arranged in the incubator chamber or the interior space of the measurement chamber can open directly into the interior space of the incubator chamber without the need for a dedicated flow path. As the measurement chamber, a section of the flow path through which the flow is passed can also be considered. Along this section, at least one measurement area of ​​at least one VOC sensor is arranged. The measuring chamber can have an inlet opening through which the gas to be measured enters the measuring chamber and in particular an outlet opening through which the gas to be measured leaves the measuring chamber.

[0048] The sensor arrangement in particular comprises at least one temperature sensor and / or an air humidity sensor and / or a pressure sensor, the latter preferably being arranged to measure the gas atmosphere in the measuring chamber.

[0049] At least one measuring area of ​​at least one VOC sensor is preferably arranged in a section of the measurement chamber located between such inlet and outlet openings, as viewed along a linear connection between such inlet and outlet openings. At least one measuring area of ​​at least one VOC sensor is preferably parallel to a flow direction, in particular a main flow direction in the measurement chamber. Such a flow direction in particular follows a line, in particular a straight line, connecting the inlet and outlet openings of the measurement chamber. At least one measuring area of ​​at least one VOC sensor is preferably arranged parallel to a side wall of the measurement chamber and / or forms the side wall of the measurement chamber. In this case, the side wall is in particular an inner wall of the measurement chamber, along which the flow of the measured gas / atmosphere flows. By such measures, the gas atmosphere possibly discharged by the separation of VOCs in the measurement area is replaced by the original gas atmosphere, so that in particular the concentration of VOCs from the gas atmosphere is as constant as possible along the measurement area.

[0050] It is possible and preferred that the measurement areas of the VOC sensors are arranged parallel to one another and in particular parallel to the flow direction through the measurement chamber. It is possible and preferred that the measurement areas of the VOC sensors are arranged parallel to one another and / or in particular parallel to the flow direction through the measurement chamber. The measurement areas can surround a flow section through the measurement chamber and in particular can be arranged concentrically around such a flow section or flow direction. The measurement areas are arranged in particular around a flow section or flow direction such that a gas volume section located in the measurement chamber and flowing through the measurement chamber contacts several or all of the measurement areas of the VOC sensors simultaneously. This in particular ensures that the same gas composition prevails in the measurement areas, in particular that an upstream separation of VOCs in the upstream sensor does not lead to a different gas composition being measured in the downstream sensor.

[0051] The flow path is preferably formed by at least one gas conduit, one end of which opens in particular into the incubator chamber and the other end of which opens in particular into the measuring chamber.

[0052] At least one valve device may be provided, which is controlled by an electronic control device of the incubator or sensor device, by which the flow passage of at least one flow passage is opened or closed, in particular also throttled. The valve device may in particular have at least one directional valve, in particular at least one 3 / 2-way valve. The incubator or sensor device may in particular have a purge gas reservoir, in which a purge gas, in particular N2 or a noble gas, for purging the measurement chamber is contained, which is connected to at least one flow passage by a valve. The at least one directional valve may be configured in a first switching position to open the flow passage of the valve between the incubator chamber and the measurement chamber and simultaneously close the flow passage of the valve between the purge gas reservoir and the measurement chamber, and in a second switching position to close the flow passage of the valve between the incubator chamber and the measurement chamber and simultaneously open the flow passage of the valve between the purge gas reservoir and the measurement chamber. Instead of a purge gas reservoir, a connection for supplying a purge gas can also be provided, to which a purge gas reservoir can be connected or to which a purge gas flow (e.g. a conveyance of - in particular filtered - ambient air) can be supplied.

[0053] Preferably, the incubator or the sensor device has a gas conveying device, in particular a fan or a pump, by means of which the gas atmosphere is conveyed from the incubator chamber through a flow path into the measuring chamber. The measuring chamber preferably has a flow path, in particular at least one gas conduit, through which the gas atmosphere is conveyed from the measuring chamber. In particular, the gas atmosphere is guided from the measuring chamber into the surroundings of the incubator, in particular into a housing region of the incubator that is open to the surroundings.

[0054] However, it is also possible and preferred to provide a return flow path for the gas leaving the measuring chamber into the incubation chamber, thereby preventing loss of incubation gas, in particular CO2. Preferably, the returned gas is guided through a filter device, which may in particular comprise a HEPA filter. The filter device is in particular configured to filter out substances and particles that the measuring chamber adds to the gas.

[0055] Preferably, at least one flow path, in particular a gas line, connecting the incubator chamber and the measurement chamber upstream or downstream of the measurement chamber, in particular also in at least one section outside the at least one measurement chamber, is insulated by an insulation device. The insulation device can have a double wall or a layer of insulation material. The insulation layer can in particular have an air pocket with an insulating effect.

[0056] Preferably, at least one flow path, in particular a gas conduit, connecting the incubator chamber and the measurement chamber upstream or downstream of the measurement chamber is in contact with a temperature control means, in particular a heating device, which warms the flow path, in particular to the temperature of the incubator chamber or even higher. In particular, the at least one flow path may be guided along the wall of the - in any case already - thermostated incubator chamber. Such measures are intended to prevent condensation effects from occurring and the VOCs from being altered or precipitated due to temperature.

[0057] The gas atmosphere of the inner space of the incubator in particular has a different composition than the atmosphere in a cell culture vessel arranged in the inner space, which in particular is in direct contact with the volatile growth medium (cell culture medium), and in particular the gas entering the measurement chamber and the gas atmosphere of the inner space have the same composition.

[0058] The measurement area of ​​the at least one VOC sensor is preferably arranged in fluid connection with the atmospheric gas of the interior space, by virtue of the measurement area being arranged in the incubator chamber, in which case a separate measurement chamber is not particularly required, although it may also be provided. The at least one measurement area may in particular be directly adjacent to the interior space of the incubator chamber and in direct contact with the gas atmosphere of the interior space, in particular the waste heat releasing components of the at least one VOC sensor are arranged outside the incubator chamber and in particular within the periphery of the incubator chamber. Such periphery is in particular not in contact with the measurement area, in particular cooled, preferably air cooled.

[0059] It is particularly preferred that the at least one VOC sensor is arranged partially, and in particular incompletely, in the incubator chamber and / or in the measurement chamber. It is particularly preferred that at least one section of the at least one VOC sensor facing away from the measurement area of ​​the sensor is arranged outside the incubator chamber and / or the measurement chamber. In particular, it is preferred that at least one heating means or all heating means of the at least one VOC sensor are arranged outside the incubator chamber and / or the measurement chamber. In this way, electrical connection of the at least one VOC sensor to an electrical control device is possible and particularly easy. Furthermore, temperature control or cooling of the at least one VOC sensor facing away from the measurement area, in particular temperature control or cooling of the heating means, is possible and particularly easy.

[0060] By means of the gas line, in particular atmospheric gas can be transported from the incubator chamber into the space outside the incubator or is transported in this way directly. The sensor device preferably has one or preferably more than one measuring chamber, in which at least one measuring area of ​​at least one VOC sensor is arranged. The flow passage which opens into the incubator chamber at one end can open into the measuring chamber at the other end or can be divided so that it opens into several measuring chambers at several ends. In particular, N (10>=N>=1) VOC sensors can be provided per measuring chamber, in particular in the measuring chamber into which the gas line opens. In one measuring chamber, exactly one measuring area of ​​one VOC sensor can be arranged or exactly two measuring areas of a VOC sensor can be arranged. In particular, atmospheric gas from the incubator chamber can be transported into at least one, preferably each, measuring chamber, and is transported in a manner controlled in particular by an electric control device.

[0061] Preferably, the measurement chamber comprises an exhaust gas conduit arranged for conveying exhaust gas from the measurement chamber into the incubator chamber or into the space outside the incubator.

[0062] Preferably, the sensor device comprises a number of VOC sensors whose measurement areas, in particular their adsorption surfaces, are arranged in contact with the inner space of the measurement chamber.

[0063] Preferably, the sensor device has a number of VOC sensors, the measurement areas of which, in particular the adsorption surfaces of the VOC sensors, are arranged in contact with the interior space of the measurement chamber for adsorption of VOCs in the measurement areas, and the VOC sensors in each case have a heating side arranged outside the measurement chamber.

[0064] Preferably, the measuring chamber has a torus-shaped internal space, in particular in the form of a closed torus, in particular with at least one inlet opening and at least one outlet opening. The torus can be located parallel to a plane, the inlet opening can be arranged essentially on this side of the plane, in particular on this side of the torus, and the outlet opening can be arranged essentially on the opposite side of the plane, in particular on the opposite side of the torus. However, the inlet and outlet openings can also be located in this plane or intersect with this plane.

[0065] In particular, the incubator or sensor device can have a conveying means for conveying gas, by which atmospheric gas, previously removed from the incubator chamber, located in the inner space of the measurement chamber, can be circulated. The inlet and / or outlet openings can have closures, in particular controllable by an electrical control device, by means of which the corresponding openings can be selectively closed. By circulating the gas, a gas exchange is achieved in the measurement area / adsorption surface, and a long-term release of the measured gas atmosphere from the incubator chamber can be avoided. This avoids the consumption of gas, e.g. CO2, and energy, which may otherwise be required for restoring the incubator atmosphere and / or for equalizing the pressure in the incubator chamber.

[0066] Preferably, the incubator and / or the electronic control device of the incubator is configured to control the corresponding inflow volume flow of at least one incubator gas, in particular a defined incubator gas mixture, for example N2 and CO2, depending on the outflow volume flow from the incubator chamber through the flow path in the direction of the measurement chamber. This keeps the incubator atmosphere as unchanged as possible even during the measurement by the sensor device. The temperature of the incubator atmosphere, which may possibly change or decrease due to the outflow and inflow of such gases, can also be kept constant or readjusted, in particular to a target temperature, for example 37°C, by the temperature control device of the incubator, in particular its temperature adjustment device and temperature sensor.

[0067] Preferably, the sensor device is configured as an electronic nose, for which it has in particular an electronic control device and a plurality of preferably different types of VOC sensors, and in particular a purge device, by means of which at least one measuring chamber can be purged with a purge gas.

[0068] Preferably, the sensor device configured as an electronic nose or the electronic control device of the incubator comprises a data processing device with at least one data memory, the data processing device being programmed to perform at least one, two or more, or each of the following steps. Similarly, the method according to the invention may comprise such steps: i) storing in a data memory a measurement data record comprising measured values ​​of N>1 VOC sensors, in particular as a function of time, in particular within at least one time segment, wherein the measured values ​​are characteristic of the detected measurement signal of each VOC sensor, recorded in the presence of a volume of gas atmosphere originating from the incubator chamber and present in the measurement area of ​​the VOC sensor, in particular having flowed in the past; ii) determining first result measurement data from a comparison of the measurement data set with a reference data set, in particular using the difference between the measurement data set and a reference data set of N>1 VOC sensors including reference measurements, in particular recorded as a function of time, the reference measurements being characteristic of the detected measurement signals of the measurement areas of the VOC sensors, in particular of each of the VOC sensors in contact with previously flowed purge gas, recorded in the presence of purge gas originating from a purge device; iii) optionally recognising a characteristic data pattern within the outcome measurement dataset comprising said outcome measurement data, said characteristic data pattern being indicative of a given VOC, and in particular the concentration or amount of said VOC, detected in said ambient gas.

[0069] Characteristic data patterns in the result measurement dataset containing the result measurement data can preferably be taken into account by the following evaluation: contamination may be present in particular if the measured values ​​of a certain VOC sensor subset of the sensor device - optionally taking into account a tolerance for deviations from their respective reference values ​​- optionally taking into account a relative deviation - but the measured values ​​of other VOC sensors of the sensor device - optionally taking into account a tolerance - do not deviate from their reference values. Characteristic data patterns can be ascertained by prior measurement of one or more test gases with a defined VOC content.

[0070] Step iii) involves a classification algorithm, preferably developed by machine learning, in particular an artificial neural network, being used to classify said characteristic data patterns.

[0071] Preferably, the control device comprises a data processing device with at least one data memory, the data processing device being programmed to carry out a first step or two or more or all steps of the following steps, as well as the method according to the invention may comprise such steps: i) storing in a data memory a test measurement data set comprising test measurement values ​​detected, in particular as a function of time, in particular within at least one time segment, of N>1 VOC sensors, the test measurement values ​​being characteristic of the detected measurement signal of each VOC sensor recorded in the presence, in particular in the past, of a volume of a pre-known test gas, in particular having a pre-known VOC content in terms of type and / or amount, supplied to the measurement chamber and adjacent to the measurement area of ​​the VOC sensor; ii) determining second result measurement data from a comparison of the test measurement data set with a reference data set, in particular by means of a difference between the test measurement data set and the reference data set, which comprises reference measurement values ​​detected for the N>1 VOC sensors, in particular as a function of time, in particular within at least one same time segment, and determining first result measurement data which are characteristic of the detected measurement signals of the respective VOC sensors recorded in the presence of purge gas originating from the purge device, in particular in previously flowed purge gas; iii) storing a second result measurement data set including the second result measurement data, the second result measurement data set having a known data pattern characteristic of the test gas.

[0072] Said steps make it possible in particular to detect the presence of a particular VOC in a gas atmosphere, and in particular to realise a method by which the concentration of at least one VOC in a gas atmosphere can be estimated.

[0073] Preferably, a step iv) is performed, which comprises using the second result measurement data obtained in iii) as label data for training an adaptive classification algorithm, in particular a neural network, by machine learning, which can then be used to classify the measured characteristic data patterns. By such a step, it is also possible in particular to realize a method capable of detecting the presence of a particular VOC in a gas atmosphere, in particular of assessing the concentration of at least one VOC in a gas atmosphere.

[0074] Preferably, the incubator comprises an information output system, in particular a display, a speaker or a data interface to an external data processing device, for outputting information relating to such detection, in response to detection of a VOC detected by the sensor device, in particular warning information to a user or a monitoring system.

[0075] The present invention also provides a laboratory monitoring system for detecting contamination of at least one incubator chamber, comprising: at least one incubator according to the invention, at least one data processing device arranged outside the at least one incubator and in particular in data exchange connection with said at least one incubator, in particular via an intranet or the internet; It has the data processing device is programmed to obtain measurement data obtained from at least one incubator and determined by detection using a sensor device of the incubator, related to possible contamination of said incubator chambers, and to store said measurement data in a data storage device, in particular to communicate said measurement data to a further device, in particular to a PC, a mobile radio device, a smartphone or a tablet computer; Concerning laboratory monitoring systems.

[0076] The present invention also relates to a method for detecting contamination in an incubator, in particular in an incubator chamber of an incubator according to the invention, comprising: * acquiring measurement data by a sensor device having at least one VOC sensor for detecting volatile organic compounds (VOCs), the VOC sensor having a measurement area arranged in fluid communication with an ambient gas of the interior space; determining possible contamination of the gas atmosphere of the interior space by evaluating the measurement data; The present invention relates to a method for detecting contamination comprising the steps of:

[0077] The invention also relates to a retrofit system with a retrofittable sensor device for detecting possible contamination of the gas atmosphere of the inner space of an incubator chamber, the sensor device having at least one VOC sensor (11) for detecting volatile organic compounds (VOC), the VOC sensor having a measurement area, which can be arranged in fluid connection with the atmospheric gas of the inner space, the sensor device preferably having a gas conduit, which can be arranged between the inner space and the measurement area, and preferably having a pump for conveying the gas atmosphere of the inner space of the incubator chamber through the gas conduit to the measurement area. The invention also relates to such a retrofittable sensor device for an incubator. The retrofit system or the retrofittable sensor device furthermore in particular comprises an electronic evaluation device, which preferably comprises a data processing device. The evaluation device is preferably configured to record and in particular evaluate at least one measurement signal, in particular a measured value, of the at least one VOC sensor. Alternatively and / or additionally, the retrofit system comprises a program code, during execution of which in particular a data processing device of the incubator acquires and in particular evaluates in particular one measured value of the at least one VOC sensor. The programmable steps have been / are still described herein.

[0078] The present invention relates to an incubator apparatus comprising an incubator with an incubator chamber and a retrofittable sensor device as described above, said sensor device being arranged in the incubator or in the incubator chamber of the incubator for detecting possible contamination of the gas atmosphere in the internal space of the incubator chamber.

[0079] An incubator is a laboratory device or laboratory incubator. An incubator refers in particular to a laboratory device with an incubator chamber, the atmosphere of which can be adjusted or is adjusted by the incubator to a defined target temperature. In particular, it is a laboratory device that can be used to create and maintain controlled climatic conditions for various biological development and growth processes. The incubator may preferably be or include a shaker, i.e. an incubator with a movement device for moving objects placed in the incubator chamber. The incubator may be a cell culture device, a microorganism incubator (including without CO2). The incubator serves in particular to be able to create a microclimate with adjusted gas and / or air humidity and / or temperature conditions in the incubator chamber, such processes may be time-dependent. A laboratory incubator, in particular a processing device for a laboratory incubator, can in particular have a timer, in particular a timer, a heating / cooling device and preferably a regulating device for regulating the exchange gas supplied to the incubator chamber, a regulating device for the composition of the gas in the incubator chamber of the incubator, in particular for regulating the CO2 and / or O2 and / or N2 content of the gas and / or a regulating device for regulating the humidity in the incubator chamber of the incubator. An incubator, in particular a processing device for an incubator, can in particular have an incubator chamber and, more preferably, a regulating device with at least one control loop, to which, as actuation device, at least one heating / cooling device is assigned and, as measurement device, at least one temperature measuring device is assigned. The temperature in the incubator can be regulated by the regulating device. Depending on the embodiment, the humidity can also be regulated in addition. The humidity can be regulated via evaporation by heating or cooling a tray filled with water. Alternatively and / or in addition to this, a moisture evaporator can be provided as a component part of the incubator, by means of which the humidity in the atmosphere of the incubator chamber is regulated. CO2-incubators are particularly used for culturing animal or human cells.The incubator may also have an inversion device for inverting the at least one cell culture vessel and / or a shaking device for shaking or moving the at least one cell culture vessel.

[0080] The sensor device of the incubator, which may in particular be assigned to the regulating device, in particular comprises at least one temperature sensor, preferably a number of temperature sensors. The temperature sensor may for example be a Pt 100 or Pt 1000 temperature sensor. The sensor device preferably comprises a sensor for determining the relative gas concentrations, in particular for determining the CO2 and / or O2 and / or N2 content. The sensor device preferably comprises a sensor for determining the relative air humidity.

[0081] The incubator preferably has one or a single incubator chamber. Such an incubator chamber may be divided into a number of compartments. These compartments may be separated by a support plate, in particular with holes, which allows, in particular, a gas exchange between the compartments. The support plate may be arranged, in particular on its underside, to hold a sensor device or a flow passage for conducting the incubator atmosphere into the measurement chamber, and may in particular have a holder for these parts.

[0082] The incubator chamber has a chamber wall or an inner chamber wall and exactly one or at least one chamber opening, through which objects or cell culture containers can be placed inside the incubator chamber and removed from there. Such a chamber opening can be closed by a closure element movably connected to the incubator chamber, in particular an incubator door movably attached to the incubator chamber by a hinge, in particular one or more chamber doors. The incubator can have one or more inner doors, which may in particular be transparent, and can have an outer door - in particular a non-transparent - and in particular an outer door, in particular a non-transparent outer door, which thermally insulates the incubator chamber and possibly at least one inner incubator door from the environment, in particular closing or opening the chamber opening.

[0083] In the closed position of the chamber opening, the interior (synonymous with the internal space) of the incubator chamber is isolated from the surroundings so that a desired atmosphere can be set, in particular regulated, inside, preferably controlled by the incubator. The concept "gas atmosphere of the internal space of the incubator chamber" does not mean the internal space of a substantially closed hollow body arranged in the incubator chamber, nor in particular the internal space of a container of a container arranged in the incubator chamber, the opening of which is closed, in particular covered, or non-airtightly or airtightly closed. For example, such an internal space of a cell culture container usually comprises a liquid medium and a gelled air supernatant located above this liquid. In the open position of the chamber opening, gas exchange between the surroundings of the incubator and the interior of the incubator chamber is possible via such an opening. The chamber opening is usually located in the front wall surrounding the chamber opening.

[0084] The incubator chamber preferably has a number of walls or inner wall surfaces, which may in particular be connected to one another in an integral manner, in particular without edges. The walls or inner wall are preferably formed in an approximately planar shape, but may also have a wholly or partially curved shape. The incubator chamber is preferably formed in a cubic shape, but may also have other shapes, for example spherical, ellipsoidal, polyhedral. The walls or inner wall surfaces are preferably made of a low-corrosive material, in particular stainless steel, copper, brass, or plastic, in particular composite plastic. This facilitates cleaning / sterilization of the chamber interior. Apart from the chamber opening, which serves for loading / unloading the object or cell culture vessel, the incubator chamber may have at least one port for leading through appropriately dimensioned devices or gas lines and / or cable connections from the inside of the incubator chamber to its outside or to the incubator periphery. A port includes in particular an opening in a chamber wall of an incubator chamber for guiding appropriately dimensioned equipment or gas conduits and / or cable connections through from inside the incubator chamber to its outside or to the periphery of the incubator.

[0085] Typical interior sizes for incubator chambers range from 50 to 400 liters.

[0086] The incubator has exactly one incubator chamber, but can also have two or more incubator chambers, the atmosphere of which (temperature, relative gas concentration, air humidity) may in particular be adjustable individually or collectively. The incubator can have several incubator chambers, each of which may have its own chamber opening and its own chamber door for closing the chamber opening, in particular for closing a specific port. Several sensor devices may be provided, in particular one per chamber.

[0087] The incubator may have a housing that partially or completely surrounds the incubator chamber. The housing may be essentially cubic in shape and, in particular, may be so designed that the incubator is stackable. The sensor device and / or the at least one VOC sensor are preferably arranged in the housing or in a housing section, in particular fixedly connected to the housing. In this way, the sensor device forms an integral part of the incubator. However, the sensor device may also be arranged in the housing as a module, in particular as part of a retrofit system, in particular fixedly connected to the housing.

[0088] The storage area of ​​the incubator is realized in particular by a storage plate, in particular a shelf insert, which storage plate / shelf insert can in particular be made of or have such materials as stainless steel or copper or similar. The storage plate serves as a bottom plate, in particular an intermediate bottom plate. The storage plate can be removable from the incubator chamber ("storage plate insert") or can be connected to the incubator chamber in a fixedly inserted state. The incubator chamber can have a holding section or a holding frame for holding one or more storage plate inserts or insertable devices. On its underside, the storage plate can be arranged to hold a sensor device or at least one gas conduit, in particular it can have a holder for such a sensor device or gas conduit. Alternatively or additionally, at least one of the inner walls of the incubator chamber can be arranged to hold one or more storage plate inserts or insertable devices. For this purpose, a holding structure, in particular one or more projections, grooves or webs, integrally integrated into the wall can be provided. The storage plate increases the available storage space within the incubator chamber.

[0089] The holding frame for the at least one support plate is also preferably made from a non-corrosive material, stainless steel. The holding frame is preferably designed as a standing body by having at least one base section that rests on the bottom wall of the incubator chamber. However, the holding frame can also be supported on the side walls of the incubator chamber and / or suspended on the ceiling wall of the incubator chamber.

[0090] The support plate preferably (and in particular mainly completely) extends across the horizontal cross section of the incubator chamber.

[0091] Preferably, the incubator comprises a handling device for handling at least one cell culture vessel. The term "handling" means in particular that an object, in particular a cell culture or a cell culture vessel, is moved and / or transported and / or investigated and / or changed, in particular physically, chemically, biochemically or in other ways.

[0092] The handling device may be a transfer device, in which the cell culture medium is kept in motion in at least one cell culture vessel, preferably via a movement program controlled by a control program. The transfer device may be a shaking or rocking device. The transfer device preferably comprises a support device, in particular a plate on which one or more cell culture vessels are placed and / or fixed, the transfer device preferably comprises a drive, in particular in the case of a shaking device a drive, for example an oscillator drive, by means of which the desired movement program is executed. The configuration of the movement program may depend on the growth stage of the cells of the cell culture and on the type of cells, in particular the cell line. The handling, in particular the configuration and / or control of the movement program, may depend on cell growth data. The handling device may be a rocking device, in which at least one cell culture vessel is rocked. The components of the rocking device correspond to those of the rocking device, but are configured for rocking movement.

[0093] The handling device may be a transport device for transporting at least one cell culture vessel in an incubator chamber. The transport device may be a lift device having a support device on which the at least one cell culture vessel can rest. The lift device preferably has a movement mechanism and / or an electrically controllable drive mechanism for driving the movement mechanism. The transport device may further have a movable, electrically controllable gripping arm for gripping and holding the at least one cell culture vessel. The transport device may have a conveyor for moving the at least one cell culture vessel mounted thereon. The transport may move the at least one cell culture vessel in the incubator chamber, in particular to a processing position in a processing station in the incubator chamber, and away from such processing position. The control device may be configured to control the transport device depending on result data obtained from the measured values ​​of the sensor device by the evaluation device.

[0094] The sensor device, in particular the gas conduit, may further be attachable or fixed to a transport device located in the incubator chamber. The sensor device may be attached or fixed to a positioning mechanism that allows the sensor device to be moved and positioned in the incubator chamber. The positioning mechanism may include a movable robot arm and is preferably electrically controllable, in particular by a control program of the control device. In this way, the VOC concentration can be measured continuously at different positions in the incubator chamber with one sensor device or with several sensor devices in succession. The positioning mechanism may be formed as a component that can be inserted into the incubator chamber. The power supply of such a component can be carried out via a cable connection to the incubator, preferably through a wall opening, for example 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 result data obtained by the evaluation device from the measured values ​​of the sensor device.

[0095] The handling device can also be understood as a temperature control device for the incubator chamber, by means of which the atmosphere in the incubator chamber is adjusted to a desired value, in particular to 37° C. The concept of temperature adjustment refers to increasing or decreasing the temperature of the atmosphere by heating and cooling. Preferably, the internal temperature is adjusted by changing the temperature of the incubator walls. Temperature sensors of the corresponding temperature adjustment device are arranged at least at one position inside and / or outside the incubator chamber, in particular in the walls of the incubator chamber.

[0096] The incubator preferably has a user interface device, via which a user can input data to a data processing device or control device and / or output information to the user. Preferably, the incubator or such a user interface device is configured such that the user can receive information that depends on the measured values ​​of the sensor device, in particular on the result data of the evaluation device. Preferably, the incubator or such a user interface device is configured such that the user can input at least one operating parameter for the operation of the incubator or the sensor device into such a user interface device and / or obtain corresponding information from such a user interface device. In this way, by using a single user interface device, the incubator and also at least one sensor device can be influenced or controlled or information can be received from the sensor device. In particular, the sensor device can be configured to show the user measured values ​​or result data, or statistical information derived from the measured values ​​and / or the time course of the measured values ​​or result data in response to a user inquiry made by the user interface device of the incubator.

[0097] The incubator's machine-controlled processing is preferably a program-controlled processing, i.e. a processing controlled by a program. By program-controlled processing of the sample, it is understood that the process of processing is essentially performed by executing a plurality or a large number of program steps. Preferably, the program-controlled processing 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 processing is preferably performed by a digital data processing device. The digital data processing device is in particular executed by a digital data processing which is part of the control device. The data processing device may have at least one processor, i.e. a CPU, and / or may include at least one microprocessor. The program-controlled processing is preferably controlled and / or performed in response to the instructions of a program, in particular a control program. In particular in the case of program-controlled processing, practically no user activity is required, at least after the user has acquired the program parameters required by the user. The incubator's machine-controlled processing can in particular be performed in dependence on measured values ​​or result data of at least one sensor device.

[0098] Program parameters are variables which can be set in a defined way within a program or subprogram and which are valid for at least one execution (call) of the program or subprogram, e.g. set by a user, and which control the program or subprogram and cause a data output depending on such program parameters. In particular, the program parameters and / or the data output by the program influence and / or control the control of an apparatus, in particular the control of the handling by at least one handling device.

[0099] A program is understood to mean, in particular, 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 a given function, task or problem. A program is usually present as software used by the data processing device. In particular, the program can be present as firmware, in the present case, in particular as firmware of the control device of the incubator or system. A program is usually present on a data carrier as executable program data, often in so-called machine code, which is loaded into the main memory of the computing device of the data processing device. A program is processed and executed by the processor of the computer as a sequence of machine instructions, i.e. processor instructions. The term "computer program" is also understood to mean, in particular, a source code from which an executable code is generated in the course of controlling the laboratory device.

[0100] The user interface device may be a component part or a module of the incubator. The user interface device preferably comprises in each case a control device for the user interface device, a communication device for establishing a data connection via the user interface device with a laboratory device, in particular an incubator, an input device for detecting a user input of a user, an output device for outputting information, in particular a display device and / or a display, in particular a touch-sensitive display. The control device of the user interface device is preferably configured to exchange data with the control device of the incubator via the data connection.

[0101] The object which can be accommodated in the incubator chamber is in particular a cell culture vessel. The cell culture vessel is in particular transparent. The cell culture vessel is in particular made of plastic, in particular PE or PS, and in particular has a planar bottom plate forming a growth surface for the cells. Such a bottom plate may be surface treated to promote cell attachment. The cell culture vessel may be closable or closed or may be provided with a PE cap or a gas exchange cap, in particular a lid which optionally includes a filter. The cell culture vessel is in particular stackable. Particularly suitable are Eppendorf cell culture flasks.

[0102] The incubator preferably has an electric control device (synonymous with control device), which may in particular include a regulating device. The data processing device is preferably part of the incubator's control device, which controls the functions of the incubator. The functions of the control device are in particular realized by electronic switching circuits. The control device may have a microprocessor including the data processing device. The control device and / or the data processing device are preferably configured to execute a control procedure, also called control software or control program. The functions of the incubator and / or the control device and / or the evaluation device can be described in method steps. These functions may be realized as components of a computer program (code) of the control program, in particular as subroutines of the control program.

[0103] In the context of the present invention, a control device generally comprises or is a data processing device, in particular a computing unit (CPU) for processing data, and / or a microprocessor. The data processing device of the incubator control device is preferably also arranged for controlling the treatment processes and / or individual treatments carried out by one or more, in particular optional, processing devices of the incubator.

[0104] The data processing device is alternatively a device that is preferably arranged outside and separate from the incubator, also called an external device or external data processing device. The data processing device and the incubator are preferably in data connection and are preferably components of a network for data exchange. The data processing device and the incubator are components of a laboratory monitoring system according to the invention, in particular for detecting the accumulation of VOCs, in particular for detecting contamination.

[0105] In particular, the incubator has a regulation device with at least one control loop, to which at least one temperature control device is assigned as an actuating device and at least one temperature sensor is assigned as a measuring element. Although the air humidity itself is not measured by the air humidity sensor (rH sensor) and is not an input variable of the control loop, in some embodiments the air humidity can also be regulated via this. Humidity can be regulated by evaporation by heating or cooling a tray filled with water in the incubator chamber. CO2 incubators are particularly useful for culturing animal or human cells. The incubator can have a rotating device for rotating the at least one cell culture vessel and / or a shaking device for shaking or moving the at least one cell culture vessel.

[0106] When arranging the sensor device on or in the incubator chamber, it should be noted that the operation of the electrical device in the incubator chamber may generate waste heat, which may heat the chamber atmosphere to an unacceptable extent. The incubator control device may therefore be configured to control the operation of the electrical device, in particular the at least one sensor device in or on the incubator chamber, in dependence on the temperature of the chamber atmosphere detected by the temperature sensor. The incubator control device may be set to control the temperature control of the chamber atmosphere by the at least one temperature control device and the operation of the electrical device in the incubator chamber in a mutually dependent manner, in particular to compensate for undesired heating of the chamber atmosphere.

[0107] The control device may be configured such that the program parameters or control parameters of the incubator are automatically selected depending on other data. The treatment of the at least one cell culture in the at least one cell culture vessel controlled by the control parameters of the at least one cell culture corresponds in particular to the climatic treatment to which the at least one cell culture is subjected. Possible parameters, in particular the program parameters, in particular the user parameters, used to influence the climatic treatment in particular define the temperature of the incubator chamber in which the at least one sample is incubated, the relative gas concentrations of O2- and / or CO2 and / or N2 in the incubation chamber, the humidity in the incubation chamber, and / or at least one sequence parameter that influences or defines the sequence, in particular the order, of the incubation treatment program consisting of a number of steps.

[0108] The temperature control device may be a combined heating / cooling device. The temperature control device is preferably a heating device only. The heating device may in particular generate heat via electrical resistance wires.

[0109] The processes controlled by the incubator also include all thermoregulation steps that affect the physical state "temperature of the incubator atmosphere", in particular the optional automatic sterilization steps with high temperature phases of about 100°C-120°C or up to 180°C or 200°C carried out in an empty incubator chamber.

[0110] The process controlled by the incubator may further include a gas exchange process in which a part of the incubator atmosphere is exchanged according to a volumetric flow rate of a given volume per time, in particular as part of the control process, in order to set the desired gas composition of the incubator atmosphere, in particular if the chamber atmosphere, in particular the chamber pressure, changes in an undesirable manner, in particular after opening the incubator door, or if the extraction of the gas atmosphere of the incubator chamber in the measurement chamber changes in an undesirable manner. The physical state to be measured in such a case is the relative gas concentration or the relative air humidity. The incubator or its control device is preferably set to adjust the relative gas concentration or the gas values ​​detected as a result of the relative gas concentration, in particular the CO2 and / or O2 values, which are applied at a certain point as a set value for the temperature control loop. Such gas control may also include a control of the air humidity, which is performed by an air humidity sensor of the sensor device, in particular by a sensor measuring the relative air humidity.

[0111] Processes controlled by the incubator itself may also include, for example, gas transfer processes that move a portion of the incubator atmosphere according to a volumetric flow having a given volume per time, in particular in one or more variable or even constant flow directions within the incubator chamber, which can make the atmosphere within the incubator chamber more uniform, in particular in order to expose cell culture vessels at different positions to the same atmosphere on average over time.

[0112] The present invention also relates to the use of a sensor device as described herein for detecting the accumulation, in particular contamination, of volatile organic compounds (VOCs) in the gas atmosphere of the inner space of a laboratory apparatus for processing liquids, in particular biological laboratory samples, in particular living cells, in particular for detecting the accumulation, in particular contamination, of volatile organic compounds (VOCs) in the gas atmosphere of the inner space of an incubator chamber of an incubator, in particular the VOCs being in each case preferably - Microorganisms placed in the interior space: - Living cells arranged in the internal space; - Leaks from equipment parts into the internal space of laboratory equipment, in particular incubators, especially incubator chambers; It is liberated by the sensor device having at least one VOC sensor for detecting VOCs, the at least one VOC sensor having at least one measurement area arranged in flow communication with atmospheric gas in the interior space; Regarding the use of a sensor device. The at least one VOC sensor, its control and the evaluation of its measurement signals can be carried out in accordance with what is described in this document and can in particular be adapted to the requirements for detecting the respective VOCs originating from the sources mentioned.

[0113] Further advantageous configurations of the incubator, the sensor device and the method according to the invention will become apparent from the following description of the embodiments in conjunction with the drawings and the description thereof, in which the same components are primarily designated by the same reference numerals unless otherwise stated or unless the context otherwise dictates. [Brief description of the drawings]

[0114] [Figure 1] FIG. 1a shows a side-front perspective view of an incubator according to the invention according to an embodiment with the housing door closed. [Figure 1b] FIG. 1b is a side-rear perspective view of the incubator of FIG. 1a. [Figure 1c]FIG. 1c is a side-front perspective view of the incubator of FIG. 1a with the housing door open. [Diagram 2] FIG. 2 is a side-front perspective view of the incubator of FIG. 1a, with the housing door removed, in section along a plane extending parallel to the side wall and through the center of the incubator. [Diagram 3] 3a-3k each show another incubator according to a respective advantageous embodiment of the present invention. [Figure 4a] FIG. 4a shows a sensor device with a measuring chamber according to an embodiment of the invention, which can in particular be used in the incubator 1 of FIGS. 1a-2. [Figure 4b] FIG. 4b shows a cross-sectional view of the sensor device with the measuring chamber of FIG. 6a without the VOC sensor inserted and its cable. [Diagram 5] FIG. 5 shows a schematic structure of a sensor device which may correspond to FIGS. 4a, 4b and its connection with a control device of an incubator. [Figure 6] FIG. 6 shows a schematic structure of a MOX sensor that can be used in a sensor device according to the invention. [Figure 7] FIG. 7 is a schematic diagram showing gas control in VOC measurement that can be performed by the components shown in FIGS. [Figure 8] FIG. 8 is a diagram showing measurements of VOCs from DH5α grown in a cell culture flask in the incubator chamber of an incubator according to the present invention. [Figure 9] FIG. 9 is a diagram showing measurements of VOCs from CHO-CD cultures grown in cell culture flasks in the incubator chamber of an incubator according to the present invention. [Figure 10] FIG. 10 is a diagram showing measurements including those taken during measurement of VOCs from DH5a in CHO-CD medium grown in cell culture flasks in the incubator chamber of an incubator according to the present invention. [Figure 11] FIG. 11 is a diagram showing, including measurements taken during the measurement of DH5α and CHO-S in CHO-CD medium grown in cell culture flasks in the incubator chamber of an incubator according to the invention. [Figure 12] 12 is a diagram showing, including measurements during the measurement of VOCs from DH5a in CHO-CD medium grown in a cell culture flask in the incubator chamber of an incubator according to the invention. The received measurement signal of the gas sensor is plotted against time and any possible alarm times are marked (vertical black markings). [Figure 13a] FIG. 13a shows an incubator according to the invention according to a further advantageous embodiment with only one VOC sensor configured as a MOX sensor. [Figure 13b] FIG. 13b is a schematic diagram of the MOX sensor of FIG. 13a. [Figure 14] FIG. 14 shows a diagram illustrating the stepwise course of the cyclical control (temperature cycled operation, TCO mode) of the MOX sensor of FIG. 13b and the resulting cyclical course of the conductivity of the measurement area. [Figure 15] FIG. 15 shows the course of the measurement signal during one measurement period of a normalized measurement cycle, derived from the measurement signal curve during the measurement period of FIG. [Figure 16a] FIG. 16a shows the measurement signal from a sensor device with multiple MOX sensors formed as a turbine after introducing a bacterial sample inside the chamber. [Figure 16b] Figure 16b shows a measurement signal from a sensor device with a MOX sensor formed to have a single sensor based on Figures 13a and 13b after a bacterial sample is introduced into the chamber as in Figure 16a, where the measurement signal is determined in TCO mode and the secondary feature is used as the measurement signal. [Figure 17a]Figure 17a shows measurement signals of several tests from a sensor device with a MOX sensor formed with a single sensor based on Figures 13a, b after introducing ethanol into the chamber, where the measurement points or measurement signals were determined in TCO mode as the average value of the measurement signals in one measurement period. [Figure 17b] FIG. 17b shows the curves of FIG. 17b after evaluation including further mathematical transformations. [Figure 18] FIG. 18 shows the curve of FIG. 17b after subtraction of the reference course. [Figure 19] FIG. 19 shows the maximum values ​​of the curves of FIG. 19 plotted on a diagram showing the value of "alcohol concentration of sample" on the abscissa. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0115] FIG. 1a shows an incubator 1 for the growth of cell cultures, here a laboratory temperature-controlled cabinet designed as a CO2 incubator for the growth of eukaryotic cells. The incubator 1 comprises a housing 2 with a housing interior surrounded by at least one housing wall 2 and a thermostatable incubator chamber 3 (also "chamber 3") arranged in the housing with a chamber interior surrounded by at least one chamber wall for receiving laboratory samples. The outer walls of the housing are connected to each other so as to support all other components of the incubator, in particular also the sensor device 30. The housing rests on a pedestal 8. For use, the outer side of the housing side wall 2c, the front wall 2a, the rear wall 2b, and the outer side of the housing door 4 and its inner side 4a, as well as the chamber side wall, the chamber front wall 3a, and the chamber rear wall 3b are arranged vertically, i.e. parallel to the direction of gravity. The outer top 2d of the housing and the bottom side which cannot be seen, as well as the bottom and top walls of the chamber are accordingly horizontally oriented. "Downwards" always means in the present description the direction of gravity in which the incubator is aligned to be operated as intended, and "upwards" means the opposite direction. The "forward" direction means the horizontal direction towards the front side of the closed housing door. The "backwards" direction means the horizontal direction towards the rear of the incubator. The chamber is made of stainless steel and the housing is made of lacquered sheet metal.

[0116] The housing door 4 is equipped with a user interface device 5, which has a touch-sensitive display used for reading and inputting information by a user, in particular for outputting information obtained by a sensor device 20. The housing door has two hinges 9 connecting the housing door to the housing 2. The housing door is held in the closed position by locking devices 7; 7a, 7b. The housing door has a door grip 6.

[0117] In Figure 1C, the housing door 4 is shown in an open position. The chamber door 10 is attached to the front chamber wall 3a by hinges 15 and is held closed in the position shown by a manual lock 13 to prevent access to the chamber interior. However, the chamber door 10 is transparent so that a user can see inside in such a position. The chamber door is hermetically held to the front chamber wall by an annular elastomeric seal 11 on the chamber door. The inner side of the housing door 4a has an annular elastomeric seal 14 which is flush with the housing front wall and annular seal 12 when the chamber door is closed, providing an airtight shielding of the area between the chamber door 10 and the housing door 4a.

[0118] As can be seen in part in Fig. 2, the incubator is equipped with two temperature control devices for thermostating the chamber inner space 3, i.e., for regulating its temperature by thermoregulation. Some of the components 18 required for this purpose are arranged between the housing bottom wall 2e and the chamber bottom wall 3e. The heating coils of the heating circuit (not shown) of the upper heating circuit (not shown) are thermally connected and bonded to the outside of the chamber ceiling wall 3d and to the upper area of ​​the chamber side wall, here approximately the upper 2 / 3 along the height of the chamber side wall 3c. The heating coils of the lower heating circuit (not shown) are thermally connected and bonded to the outside of the chamber bottom wall 3e and to the lower area of ​​the chamber side wall, here approximately the lower 1 / 3 along the height of the chamber side wall 3c.

[0119] An insulation device 19 (19a, 19b, 19c) is provided between the chamber and the housing. The insulation device separates the chamber with the adjacent temperature control device from the housing, which is in direct contact with the environment outside it. Incubators usually work at external temperatures between 18°C ​​and 28°C. Temperature control devices or temperature control systems work particularly efficiently in such areas. The insulation device comprises a U-shaped curved insulation element 19a made of glass or mineral wool, which surrounds the chamber ceiling plate and both chamber side walls 3c. The insulation element opens to the bottom and towards the rear wall into an insulation plate 19c made of PIR foam (polyisocyanurate foam) and is terminated at the front side of the housing and chamber by an annular needlefelt strip 19a which abuts against the housing front wall 2a, the chamber front wall 3a and the inside of the seal 12. The insulation of the chamber towards the outside is optimized by the measures according to the invention.

[0120] A double housing rear wall 16 is attached to the housing rear wall 2b in order to cover the rear mounted components, in particular the measuring chamber 31 of the sensor device 30. The rear wall can be removed by means of a grip 17.

[0121] The incubator has two access ports 20, 20' on its rear side which allow for laying conduits, in particular at least one gas conduit, between the measuring chamber 32 and the incubator chamber 3 and / or laying cables into the interior of the chamber 3 through openings 20h, 20'h in the rear wall of the chamber, for example to control a sensor device arranged therein. If no access ports are required, they are filled with plugs 25 made of insulating material, for example silicone foam.

[0122] Preferably, the gas conduit 29 opens into the inner space of the incubator chamber 3, passes through the opening 20h in the chamber rear wall and / or through the opening of the port 20, passes along the chamber rear wall between the insulation 19c of the insulation device 19 so as to be tempered by such chamber wall which is indirectly tempered, and then the gas conduit 29 leaves the chamber rear wall for the first time, penetrates the insulation 19c and enters into a preferably provided measuring chamber 32, which is now located in a region of the incubator 1 separated by the housing rear wall 16 and connected to the incubator. An exhaust conduit (not seen) of the measuring chamber 32 leads preferably through the housing rear wall 16 into the periphery of the incubator.

[0123] Further advantageous configurations of the sensor device, the at least one VOC sensor and the measuring chamber and their advantageous arrangement in an incubator, in particular incubator 1, are explained on the basis of the following drawings.

[0124] Fig. 3a shows an incubator 200 with an incubator chamber 102 and an incubator housing section 103 ("external area") located outside the incubator chamber; these components are included in each incubator of Figs. 3a-3k. In Fig. 3a, gas exchange is performed from the inside of the chamber 102 through the port 105, through the chamber wall 102a, by conveying the chamber atmosphere by a conveying means 113 (pump or ventilator) to the measurement chamber 132 of the VOC sensor device 130 arranged in the external area 103 together with the control device 104, and the exhaust gas of the VOC measurement chamber 132 is discharged to the environment through the exhaust conduit 109a; purge gas 112 is led to the VOC measurement chamber through the purge gas conduit 109c and valve 109d to purge the VOC measurement chamber before measurement.

[0125] FIG. 3b shows an incubator 200: the VOC sensor control device (204) is located in the exterior region 103, the measurement region, i.e., the MOX side 211a of the VOC sensor 211 is located in the interior region of the chamber 102, the heated side 211b of the VOC sensor 211 is located in the exterior region 103, and the VOC sensor 211 is hermetically mounted in a hole 205' in the chamber wall 202a.

[0126] FIG. 3c shows an incubator 300: gas exchange is carried out from the inside of the chamber 102 by gas conduit 309 through port 305 through the chamber wall 302a by transport by pump 313 to a measurement chamber 332 of a VOC sensor device or e-nose 331 with six VOC sensors 311 arranged in the external area 103 together with the control device 304, and the exhaust gas of the VOC measurement chamber 332 is discharged to the environment via exhaust conduit 309a, and purge gas 312 is sent to the VOC measurement chamber before measurement via purge gas conduit 309c and valve 309d.

[0127] 3d shows an incubator 400: gas exchange takes place from the interior of the chamber 102 by gas conduit 409 through port 405 through the chamber wall 402a, by conveyance by pump 413, to the measurement chamber 43 of the VOC sensor device or e-nose 431 with six VOC sensors 411 arranged in the external area 103 together with the control device 404; exhaust gas of the VOC measurement chamber 432 is returned through the chamber wall 402a through port 405', via exhaust conduit 409a' and optionally filter 415, back into the chamber 102; purge gas 412 is conveyed to the VOC measurement chamber through purge gas conduit 409c and valve 409d. Optionally, a heater or heating device 417 of the conduit 409 is provided to prevent condensation.

[0128] FIG. 3e shows incubator 500: VOC sensor 511 is located on a rack plate 506 in chamber 102 and is connected by cable 507 and a cable-based signal connection to a VOC controller 504 in external area 103 via port 505 through chamber wall 502a.

[0129] FIG. 3f shows an incubator 600: a VOC sensor 621 is mounted on a rack plate 606 within the chamber 10 and connected to a VOC controller 604 in the external region 103 through a portless chamber wall 602a′ by a cable-free, wireless device 621a, 604a-based signal connection.

[0130] FIG. 3g shows an incubator 700: a VOC sensor 711 is attached to the chamber wall 702a by a magnetic fastener 708 (Magnethefter) within the chamber 102 and is connected to a VOC controller 704 in the external region 103 via a port 705 through the chamber wall 702a by a signal connection based on a cable 707.

[0131] FIG. 3h shows an incubator 800: a VOC sensor 821 is connected to the chamber wall 802a by a magnetic fastener 808 within the chamber 102 and is connected to a VOC controller 804 in the external region 103 through the port-less chamber wall 802a' by a cable-free, wireless device-based signal connection based on 821a, 804a.

[0132] 3i shows an incubator 900: a measuring chamber with a ring profile and circulating chamber gas is shown. Gas exchange takes place by means of gas conduit 909 from the interior of chamber 102 through port 905 through chamber wall 902 to measuring chamber 932 of a VOC sensor device or e-nose 931 with here six VOC sensors 911d, arranged in the external area 103 together with control device 904, by conveyance by pump 913, and after closing of valves 909d and 909g, the exhaust gas from VOC measuring chamber 932 is circulated through measuring chamber 932 by pump 916 via circulation conduit 909f, thus allowing continuous convection of VOC-containing chamber gas without significant damage to the gas or atmosphere of chamber 102. Purge gas 912 is sent to the VOC measuring chamber via purge gas conduit 909c and valve 909d. As a result of the circulation of the gas volume, no further gas volume is removed from the chamber 102, thereby minimizing chamber gas losses.

[0133] Fig. 3k shows an incubator 1000: the figure shows a measurement chamber formed in a circular manner for measuring the circulating gas. Gas exchange is carried out by means of a gas conduit 1009 from the interior of the chamber 102 through a port 1005 through the chamber wall 1002a to a ring-shaped measurement chamber 1042 of a VOC sensor device or e-nose 1041, here equipped with 12 VOC sensors 1011d, by conveyance by a pump 1013, and after closing of the corresponding valve, the exhaust gas is circulated by the pump 1013 through the VOC measurement chamber 1042, allowing continuous convection of the VOC-containing chamber gas without significantly impairing the gas or atmosphere of the chamber 102; the purge gas 1012 is conveyed to the VOC measurement chamber via a purge gas conduit 1009c and a valve 1009d. Advantages: chamber gas is removed from the chamber over the shortest possible distance, so little condensation occurs; but only the volume required for the narrow ring-shaped VOC measurement chamber needs to be removed from the chamber 102; the gas volume circulates during the measurement; as a result, there is less loss of chamber gas compared to structures with gas supply and exhaust gas conduits to the surroundings.

[0134] FIG. 4a shows a sensor arrangement 61 with a measuring chamber 62 according to an embodiment of the invention in a side perspective view from above. This sensor arrangement can be used in particular in the incubator 1 of FIGS. 1a-2. The measuring chamber is a hollow spindle-shaped body, which in FIG. 4a has at its upper end an inlet opening 63 for the inflow of ambient gas from the incubator chamber by means of a gas conduit 64 and for the outflow via an outlet conduit 67. The measuring chamber can be fixed to the incubator by means of a holder 66, in particular it can be screwed, soldered or in another way fixedly connected to the incubator, in particular to a housing wall or a chamber wall. The measuring chamber 62 has a partial hollow body 62a, into which a gas conductor 68 is arranged and which is covered by a cover part 62b. The parts 62a, 6sb and 68 are fixedly connected to one another. Outside the measurement chamber 62 one can see the rear faces 65a-65i of here nine MOX-VOC sensors, which have a measurement area or heated MOX adsorption surface (not visible) on their front side facing and parallel to the central longitudinal axis A of the measurement chamber.

[0135] FIG. 4b shows, by cutting through the model, the open sensor device 61 with the measuring chamber of FIG. 6a in a side perspective view, without the VOC sensor inserted and without its cable.

[0136] The measuring chamber 62 has an upper hollow conical section 62A, a central hollow cylindrical section 62B and a lower hollow conical section 62C, as shown in Fig. 4b. At the top of the hollow conical section 62A there is an inlet opening 63 for the gas, and at the tip of the hollow conical section 62C there is an outlet opening 63 for the gas. The main flow direction A results from a straight line connecting the centers of the circular inlet opening 63 and the circular outlet opening 67. At the top of the gas guiding body section 68b facing the inlet opening there is arranged an ambient sensor (not shown; pressure, temperature, air humidity), which, like the nine VOC sensors, is connected to an electronic evaluation device for signal exchange.

[0137] The gas guide is spindle-shaped and is arranged coaxially with the axis A of the hollow spindle-shaped contour of the outer wall of the measuring chamber 62, so that between the inside of the outer wall of the measuring chamber 62 and the outside of the gas guide a sleeve-shaped flow path or a flow path with a ring-shaped cross section is created. In this way, the gas is guided uniformly and in particular with the formation of eddies (i.e. as laminar as possible) past the measuring areas of the VOC sensors 65a-65i, which are tightly pressed against the circular openings 62c in the outer wall of the measuring chamber 62, so that in each of the nine openings 62c the same surface of the MOX adsorption surface of the measuring area of ​​each VOC sensor is in contact with the gas flowing past parallel to the flow direction A. The gas is guided by the guide elements and the gas guide. Due to the guide elements and the uniformity of the gas flow, the measurements performed by the sensor device 61 are particularly sensitive, moreover reproducible and reliable. The back side of the MOX-VOC sensor is placed outside and not in contact with the measurement chamber, thus minimizing the heat transfer between the heating element of the sensor and the measurement chamber. The back side can be further cooled easily by convection / airflow.

[0138] Example of an incubator with a sensor device and an electronic nose The incubator according to the invention described below has a structure according to Figures 1a-2 and uses the sensor device 61 of Figures 4a, 4b (to realize the sensor device 30). The sensor device 61 is configured as an electronic nose with a total of nine different VOC sensors.

[0139] VOC Basics: During the metabolism of microbial organisms and cells, VOCs are released. The sensor device 61 is constructed according to the principle of an electronic nose and measures the VOCs. The sensor device can draw conclusions about contamination of the cell culture or about processes in the cell culture or in the incubator chamber that are related to the VOC concentration in the incubator chamber. A prerequisite for this is that the gas sensor has sufficient selectivity and sensitivity for the VOCs generated in order to detect microbial contamination.

[0140] A total of nine gas sensors with different selectivities are installed here. They therefore react differently to the VOCs carried by the microorganisms and generate characteristic measurement signal patterns. Measurements are performed especially during the growth period of the biological samples, so that the measurement signal patterns can be recorded as a function of time. The measurement signal patterns of the biological samples contain information that must be analyzed and compiled into semantic statements. The detectability of microbial contamination of cell cultures is described in more detail below. Each of these nine gas sensors can also be used in a sensor device with eight or fewer gas sensors or even a single gas sensor. Furthermore, not only VOCs originating from microbial organisms can be detected, but also VOCs originating from the release of the incubator equipment components immediately after production.

[0141] A variety of gas sensors can better distinguish between different microbial organisms and cells. For example, in some cases, similar measurement signal patterns may occur during different types of contamination, but the signal curves of individual gas sensors are characteristically different. The advantage of using multiple different gas sensors is that the information content of the measurement increases.

[0142] The sensor arrangement 61 utilizes a measuring chamber (MK), a gas conduit system (GS) and a processing unit (VE). The MK contains a gas sensor (VOC sensor) for measuring the VOC. The GS directs the VOC to the MK by means of an actuator. The VE controls the GS, reads out the gas and ambient sensors, processes the data and provides a communication interface to the incubator. The VE contains an electronic control of the sensor arrangement including an evaluation device with a data processing device. The microcontroller of the control device is here a Raspberry Pi 3 B (Raspberry). The communication interface allows the flow of information between the AI ​​module and the measuring chamber and thus the control of the sensor arrangement 61 by means of a user interface.

[0143] In Fig. 5, the general structure of the sensor device 61 and its connection with the control device of the incubator, also called AI module, is shown. The MK includes a gas sensor, an ambient sensor, an inlet and an outlet. The GS directs either the purge gas or the VOC (i.e. chamber ambient gas) into the MK with the help of gas conduits from valves and pumps. The VE is connected with the GS and the MK through electrical leads. The VE controls the GS, reads the gas and ambient sensors, processes the data, and provides a communication interface to the incubator. The communication interface allows the flow of information between the AI ​​module and the sensor device 61, and thus allows the control of the sensor device 61 using a user interface (user interface device).

[0144] In this embodiment, the MK is purged before the introduction of the VOCs so that the same starting conditions are provided as much as possible before each VOC analysis. The purging process is preferred to generate comparable measurement results. If the sensor device 61 is not utilized, gases may enter the MK from the environment or VOCs from previous VOC measurements may remain in the MK. Preferably, a purge gas of constant composition is always used. In order to keep the proportion of variable gases in the purge gas low, nitrogen 5.0 is preferably used as the purge gas. This purge gas here has a purity of >99.999%.

[0145] The MK has an inlet and an outlet (inlet and outlet). Through the inlet, the purge gas or VOC is introduced into the MK. Upstream of the inlet there is a Y-joint, which connects the purge conduit with the VOC conduit. Through the outlet the gas leaves the MK again. The inlet and outlet are preferably located opposite and centrally on the respective outer walls of the MK to ensure as uniform a flow and distribution of the gas as possible.

[0146] As the gas sensor (VOC sensor), a MOX sensor is preferably used.

[0147] There are many different analytical methods to detect VOCs, one of which is the electronic nose. By utilizing a sensor array, the electronic nose uses pattern recognition to generate a fingerprint of a given odor and distinguish this fingerprint from other odor fingerprints. In this way, the electronic nose mimics the mammalian olfactory system and is able to recognize the odor as a whole, and therefore identify the source of the odor. For example, microbial identification can be performed by drawing source conclusions based on the detected mixture of characteristic VOCs.

[0148] The measurement system of the electronic nose is composed of, inter alia, a sample induction unit, a detection unit and a calculation unit, and the gas sensors used are preferably selected to be sensitive to the gas molecules generated, with the individual gas sensors reacting to them with different intensities. Here, metal oxide semiconductor (MOX) gas sensors are used, which belong to the class of chemical sensors. Chemical sensors have a detection layer that converts chemical interactions into electrical signals, and are not only inexpensive but also can be used for continuous measurement operations.

[0149] Structure and function of MOX sensors: The sensor mechanism is based on the fact that depending on the concentration of the target gas, the electrical conductivity of a gas-sensitive metal oxide layer or semiconductor is changed, so that the presence and amount of the target gas is determined. Typically, MOX sensors consist of four elements: a gas-sensitive metal oxide layer, an electrode, a heating element, and an isolating layer (see Figure 6).

[0150] FIG. 6 shows the schematic structure of the MOX sensor. The MOX sensor consists of four elements: a gas-sensitive metal oxide layer, an electrode, a heating element, and an isolation layer. The heating element is separated from the gas-sensitive metal oxide layer and the contact electrode by an isolation layer. The gas-sensitive metal oxide layer is heated by the heating element, and oxygen molecules from the environment are adsorbed on the surface of the gas-sensitive metal oxide layer. The adsorbed oxygen molecules capture electrons from the conduction band of the semiconductor, and energy barriers are formed. These energy barriers block part of the electron flow in the semiconductor, thus deteriorating the electrical conductivity or increasing the resistance of the gas sensor. As soon as reducing gases (target gases) are present, they react with the bound oxygen molecules. The oxygen molecules are released from the surface of the gas-sensitive metal oxide layer, and the electrical conductivity increases or the resistance decreases.

[0151] The manufacturer usually specifies the ambient conditions under which the MOX sensor provides valid measurements and how strongly the measurements are affected by these ambient conditions. To provide an overview of how strongly the environmental conditions affect the VOC measurements, an ambient sensor is additionally placed in the center of the MK. Relevant environmental conditions include humidity, temperature, and ambient pressure.

[0152] The process of VOC measurement is preferably divided into two stages: purging and introduction of VOC. The incubator with the sensor device is first initialized for the measurement and purged. The gas sensor is preferably continuously read out for the measurement and temporarily stored. If necessary, the user can permanently save the temporarily stored data and possibly export it. The VOC measurement itself is started and stopped by the user or automatically by the incubator by controlling the GS. The elements to be controlled are the valves and the pump. To control the VOC measurement, for example, a purge process is started. Valve 1 (V1) is opened, valve 2 (V2) is closed and pump (P) is deactivated (see the top of FIG. 7). If it is desired to end the purge process and start the supply of VOC, valve 1 (V1) is closed, valve 2 (V2) is opened and pump (P) is started (see the bottom of FIG. 7). To end the VOC measurement, pump (P) is shut off and valve 2 (V2) is closed. The sensor device is preferably supplied with voltage via the circuitry part of the incubator, which concerns the gas sensors VE, MK, valves and pumps GS.

[0153] FIG. 7 shows a schematic diagram of the gas control during VOC measurement. This is preferably divided into purging and aspiration of VOC. Gas-carrying components are marked in green, non-carrying components in red. During the purging process, valve 1 is open, valve 2 is closed, the pump is deactivated, and the purge gas flows through the measurement chamber. During aspiration of VOC, valve 1 is closed, valve 2 is open, the pump is activated, and the VOC flows through the measurement chamber.

[0154] The MK consists of an aluminum cast chamber with a screwable roof and contains various types of gas sensors (MQ1, MQ2, MQ3, MQ4, MQ5, MQ6, MQ7, MQ8, Q9 and MQ135 or designations 65a-i, conventionally available from HANWEI ELETRONICS CO., LTD) and an ambient sensor (BME680). The ambient sensor provides the required environmental parameters of temperature, humidity and pressure and was placed inside the MK. The gas sensors were selected to be primarily selective for the substance groups of potentially occurring VOCs and were placed adjacent to the MK according to the established concept. The connections between the gas sensors and the MK were sealed with silicone. The selectivity of each of the gas sensors is listed in the details section of Table 1. [Table 1]

[0155] As a sample to prove the function of the sensor device and to generate contamination in the incubator chamber, Escherichia coli of the strain DH5α (DH5α) was used, which can be frequently encountered in routine laboratory work. Various VOCs are emitted by DH5α (see Table 2). The VOCs belong to the substance groups benzols, alkylbenzols, ketones, alcohols, alkanes, terpenes, acids, carboxylic acids, esters, aldehydes, alkenes, heterocyclic amines and indoles. The majority of the VOCs listed belong to the substance group alcohols. Some of the gas sensors used are selective for gases of the substance groups alcohols, alkanes, benzols and aminos according to the manufacturers' declaration. Correspondingly, gas sensors MQ2, MQ3, MQ4, MQ5, MQ6, MQ9 and MQ135 are adapted to respond to the VOCs of DH5 and allow recording an increase in the measurement signal. Since the majority of the VOCs produced belong to the alcohol group, the gas sensors MQ2, MQ3 and MQ135 produce higher measurement signals than the other gas sensors. [Table 2]

[0156] Chinese hamster ovary cell cultures (CHO) are a cell type routinely encountered in laboratories. The VOCs emitted by CHO belong to the substance groups of alkanes, aldehydes, esters, benzols, ketones, pyrazoles, oximes, and alcohols. The majority of the VOCs listed belong to the substance group of alkanes. Some of the gas sensors used have selectivity for gases of the substance groups of alcohols, alkanes, and benzols according to the manufacturer's declaration. Thus, gas sensors MQ2, MQ3, MQ4, MQ5, MQ6, MQ9, and MQ135 are adapted to react to VOCs of CHO and can record an increase in the measurement signal. As the majority of the VOCs generated belong to the alkane group, gas sensors MQ2, MQ4, MQ5, MQ6, and MQ9 should generate a higher measurement signal than the other gas sensors. As in the case of DH5, the cell cultures must have consistent growth kinetics characteristics at each test. In contrast to DH5, CHO was not cultured independently but was prepared by the applicant and cultured according to an internal standard procedure.

[0157] The evaluation device (VE) uses an algorithm to recognize whether a contamination is present in the test sample (CHO with / without DH5α). The developed algorithm is based on the sequential CUSUM analysis technique (also called CUSUM Control Chart) and was first published by Page. Evaluation by AI algorithms, especially neural networks, is also possible. The CUSUM analysis method is utilized to monitor deviations in the running process. i Let x be the i-th observation. A process is divided into two states: it is in control or it is not. If the process is in control, then x i follows a normal distribution with mean μ0 and standard deviation σ. μ0 is often chosen to be smaller than x so that the process remains under control. i is interpreted as a target value that must be as close as possible.

[0158] Figure 8 shows a diagram containing measurements during the measurement of VOCs from DH5α grown in a cell culture flask in the incubator chamber of an incubator according to the invention. DH5α was measured in LB medium and the recorded measurement signal of the gas sensor was plotted against time. To record the measurement data shown in Figure 8 (as well as Figures 9 and 10), the following steps were carried out, in particular by programming the data processing device of the incubator: Within a first time period from the start of the measurement at time zero, the measurement chamber with the measurement area of ​​the different type of MOX sensor is purged with a purge gas, here nitrogen. With the purge gas flowing past the measurement area, the MOX sensor measures reference measurement values ​​(in the form of a voltage, respectively) essentially in parallel and consecutively in this first time period. Such a first time period is approximately 5 hours in FIG. 8a and approximately 7 hours in FIGS. 8b and 8c. In a second time period immediately following the first time period, the gas conduit serving as the inlet is opened by a valve, which simultaneously stops the flow of purge gas into the measurement chamber. As a result, a defined volume of gas atmosphere flows into the measurement chamber and then flows out again from this measurement chamber, for example through an exhaust channel. This volume flows past the measurement area during a second time period. Within this second time period, the MOX sensor measures measurement values ​​essentially in parallel and consecutively in time. In figure 8a the second period is from the end of the 5th hour from the start of the measurements, and in figures 8b and 8c from the end of the 7th hour from the start of the measurements to the end of the 22.5th hour from the start of the measurements, respectively. For each MOX sensor, the reference measurement determined within the first hour forms a "baseline", to which the measurements are considered: the difference between the measurement at a certain point in time and the reference measurement can be considered as a measurement of contamination (result measurement data). If such difference is zero, there is no contamination. If the difference is here for example greater than zero, contamination is present. Most MOX sensors detect contamination by non-zero result measurement data.

[0159] During such types of measurements (Figures 8, 9, 10) and subsequent evaluation, the data storage device is programmed to perform the following steps: (i) storing a measurement dataset in a data memory, which here comprises measurement values ​​of N=9>1 VOC sensors, the measurement values ​​being characteristic of the detected measurement signal of each VOC sensor, the measurement signal being detected in the presence of a volume of gas atmosphere originating from the incubator chamber and applied to the measurement area of ​​the VOC sensor; (ii) determining first result measurement data from a comparison of the measurement dataset with a reference dataset, in particular by means of the difference between the measurement dataset and the reference dataset, in particular comprising reference measurement values ​​of N>1 VOC sensors recorded as a function of time, the reference measurement values ​​being characteristic of the detected measurement signal of each VOC sensor recorded in the presence of a purge gas originating from a purge device and present in the measurement area of ​​the VOC sensor.

[0160] Optionally, (iii) recognizing a characteristic data pattern in a result measurement dataset comprising said result measurement data, said characteristic data pattern being representative of a given VOC or VOC mixture detected in said ambient gas, in particular also the concentration or amount of said VOC. For example, result measurements of different types of MOX sensors can record a characteristic data pattern at one or more measurement time points, in particular taking into account a common scaling factor or taking into account a normalization factor.

[0161] 9 shows a diagram containing measurements during the measurement of VOCs from a CHO-CD medium grown in a cell culture flask in the incubator chamber of an incubator according to the invention, which was measured by the sensor device 61 and the received measurement signal of the gas sensor was plotted against time.

[0162] 10 shows a diagram containing measurements during the measurement of VOCs from DH5a in CHO-CD medium grown in a cell culture flask in the incubator chamber of an incubator according to the invention. DH5a in CHO-CD medium was measured and the measurement signal received by the gas sensor was plotted against time.

[0163] 11 shows a diagram containing measurements when measuring DH5a and CHO-S in CHO-CD medium grown in cell culture flasks in the incubator chamber of an incubator according to the invention, where DH5a and CHO-S in CHO-CD medium were measured and the measurement signal received by the gas sensor was plotted against time.

[0164] 12 shows a diagram containing measurements during the measurement of VOCs from DH5a in CHO-CD medium grown in a cell culture flask in the incubator chamber of an incubator according to the invention. The received measurement signal of the gas sensor is plotted against time and possibly present warning times are marked (vertical black markings).

[0165] Based on the test results, it is shown that the sensor device 61 can detect the increasing microbial contamination of the cell culture. The gas sensor system can thus contribute to prevent the microbial contamination from going unnoticed and thus avoid further problems in the application of cell culture. The integration of the gas sensor system in the CO2 gas sensor system is effective and makes the gas sensor system easily usable in the laboratory environment of the CO2 incubator.

[0166] Example of an incubator equipped with a sensor device having a single VOC sensor Fig. 13 shows an incubator 50 for incubating living cell cultures. The incubator 50 comprises a housing 52, an incubator chamber 53 for receiving objects, in particular cell culture containers, in an internal space of the incubator chamber that has a controllable gas atmosphere in the housing and that can be closed by an incubator door 54, and a sensor device for detecting the accumulation, in particular contamination, of volatile organic compounds (VOCs) in the gas atmosphere of the internal space, the sensor device having exactly one VOC sensor 51 for detecting the VOCs and the VOC sensor 51 having a measurement area 51a, the VOC sensor 51 being a thick film sensor, MOX sensor, commercially available through Figaro USA, Inc., named Figaro TGS2602. Such a sensor can also be used in an incubator with a sensor device having two or more VOC sensors. This also applies to the aspects of its installation in the incubator, its control by a constant or variable voltage and the evaluation of the measurement signal.

[0167] The sensor 51 is fixedly attached to the inner wall of the chamber 53, so that the metal oxide surface serving as the measurement area is arranged in fluid connection with the ambient gas of the inner space. An electrical cable 51d passes through the housing 52 in a housing region in which the electrical control device 51' is arranged, through a port 52a in the chamber wall. To the control device 51', the sensor 51 is connected by the cable 51d. The sensor 51 is controlled and evaluated by the control device 51'. The heating element of the sensor 51 is operated by the control device with a measurement voltage U_H_setpoint measured in volts. The measurement voltage is applied to the electrode 51b of the sensor 51 (FIG. 13b). An electrical resistance value measured in ohms, for example an electrical resistance R_sensor, or a conductivity G_sensor measured in siemens, is further detected via the electrode 51c. The corresponding measurement signal is evaluated by the control device 51'. The electrical resistance value output by the sensor can be output as a voltage (volts). The desired measured value R_sensor or G_sensor can be derived based on a known dependency, in particular a proportionality, in that the output voltage value is proportional to the desired measured value R_sensor or G_sensor.

[0168] The control device 51' serves as an evaluation device and includes a data processing device. The evaluation device is programmable with a program code and is programmed in particular according to such program code to carry out the following steps: receiving a measurement signal R / G_sensor, in particular of measurement data, of a MOX sensor, in particular receiving a series of measurement signals successively in time, in particular over the duration of a measurement time Δt, said measurement signals forming in particular a measurement course over time of one MOX sensor, comparing the measurement signal with a reference value; determining, based on the results of such comparison, whether there is a change in the concentration of VOCs in the gas atmosphere of the interior space, in particular a change which is characteristic for contamination of the interior space.

[0169] The control device 51' is arranged to control the heating element of the sensor 51 with a periodically varying voltage UH-setpoint, thereby generating a correspondingly periodically varying temperature at the metal oxide surface. Such an operation of the sensor device is also called "temperature cycled operation (TCO)". For this, the heater is controlled here with a voltage UH-setpoint having a step-like progression. The voltage provides a number of different values ​​per heating period T, here the voltage values ​​4.0 volts, 4.5 volts and 5.0 volts. This is shown in FIG. 14. Each such voltage value is adjusted for a defined portion of the heating period T. The heating period is preferably between 5 seconds [s] and 30 s, preferably between 15 s and 25 s, preferably between 17 s and 23 s, and here is about 20 s. From the control a periodically varying measurement signal with a measurement period T results.

[0170] In the case of periodic measurement signals, the evaluation is preferably carried out by statistically evaluating one or preferably more periods of the measurement signal. Preferably, the data processing device is programmed to determine the average course of one measurement period. This may involve superimposing the values ​​of M measurement periods and then multiplying such an added period course by the reciprocal 1 / M. In this way, the measurement signal is smoothed and the influence of measurement artifacts is reduced.

[0171] Preferably, the data processing device is programmed to derive from the signal of a single measurement period or from the average course of the measurement period at least one secondary value related to a characteristic of the measurement period, called secondary characteristic. As shown in Fig. 15, the secondary value may be a slope present at a characteristic time point of the measurement period, for example at a transition point of the voltage value. As can be seen in Fig. 15, the characteristic slope can in particular be recorded just before or just after such a time point. For further evaluation, the secondary value can be compared, as described above, with at least one reference value corresponding to such secondary value.

[0172] Preferably, the data processing device is programmed to determine an average value of a number of measurement signals, in particular an average value of a number or substantially all of the measurement signals during one measurement period, which can be compared, as described above, with at least one reference value corresponding to such an average value for further evaluation.

[0173] In Fig. 16a the time course of the measured values ​​determined with the sensors of the "turbine" type sensor arrangement 61 is shown. The measurement signal of each sensor reacts with a time delay to the addition of bacteria, i.e. a VOC source, into the chamber inner space, so that in this case an increase in the measurement signal can be detected after about 15 hours. In Fig. 16b, in a comparative experiment a single sensor (Figaro as shown in Figs. 13a, 13b) was operated in TCO mode. The measurement point is one mean value of one cycle or one measurement period T = 20 seconds, respectively, specified according to the sensor control shown in Fig. 14. A secondary feature of the measurement signal period was evaluated, in this case the quotient m0e / m_ges. The string "m0e" stands for the secondary feature. Each measurement cycle consists of several temperature cycles. Each temperature cycle has a number starting with 0. Each temperature cycle has a start "s" and an end "e". There are two classes of features: the mean value "m" and the slope "s". According to this the quotient means: m0e=mean value at the end of the 0th cycle / m_ges=mean value over all measurement cycles.

[0174] FIG. 17a shows a series of different curves of the evaluated measurement signal (conductivity of the measurement layer in Siemens) acquired in different experiments, superimposed for better comparison. The measurement setup corresponds to the device of FIG. 13a,b, operated in TCO mode, measurement period 20 s. Each curve, distinguishable by color or scale, corresponds to one experiment. The volume percentage content of ethanol (e.g. 0.1% to 0.4%) was varied in a predefined total volume of ethanol-water mixture, which was always placed in the same open container inside the chamber. The reference time is the moment when the chamber door is closed again after a brief insertion of the sample container. In FIG. 17a, the mean value, here smoothed, of the measurement signal of the measurement period is plotted for each cycle (measurement period), “m_ges smoothed”. In Fig. 17b, for normalization of the measurement signals, the value "m_ges smoothed" is further divided by the minimum value of the respective curve at the reference time and the value 1 is subtracted from this quotient (m_ges smoothed / Min-1). All signals are normalized to such a value (mges / min), in which case the minimum value is equal to 1. Subtracting 1 from the measured value then pulls the curve towards zero.

[0175] In FIG. 18, the maximum values ​​of the measurement curve of FIG. 17b are plotted against the respective alcohol concentration (ethanol in water, wt.%). On the one hand, it can be seen that the measurement setup is efficiently suitable for detecting and quantifying the EtOH-VOC inside the chamber by means of a chemical MOX sensor, since the maximum values ​​of the evaluated quantity (m_ges smoothed / Min-1) lie on a straight line. From the position of the maximum of the curve and the linear slope from the respective further comparative experiments (m_ges smoothed / Min-1) of unknown ethanol concentrations, the ethanol concentration of the sample can be determined. This test is very suitable for detecting bacteria inside the chamber, since the main component of the VOCs liberated during the metabolic processes of bacteria is alcohol. The slope of the line itself is also a measure of the sensitivity of the measurement setup, meaning that the greater the slope, the easier the evaluated quantity can be discerned. Any estimation of the detection limit, detection limit and quantification limit of the measurement setup / measurement method can be determined according to DIN 32645. For FIG. 18, the slope takes into account the drift of the measurement signal with respect to time and the noise of the measurement signal.

Claims

1. An incubator (1; 50; 200; 300; 400; 500; 600; 700; 800; 900; 1000) for incubating living cell cultures, said incubator comprising: - an incubator chamber (2) having a controllable gas atmosphere for receiving an object, in particular a cell culture container, in a closable internal space of said incubator chamber; A sensor device (11; 21; 31; 41) for detecting the accumulation, in particular contamination, of volatile organic compounds (VOCs) in the gas atmosphere of the interior space, the sensor device having at least one VOC sensor (11) for detecting the VOCs, the at least one VOC sensor having at least one measurement area, the measurement area being arranged in fluid connection with the atmospheric gas of the interior space; The incubator has:

2. 2. The incubator according to claim 1, further comprising a flow path, in particular at least one gas conduit, leading from the inner space of the incubator chamber into a measuring chamber arranged in the outer space of the incubator chamber, so that atmospheric gas from the incubator chamber is transported into the measuring chamber.

3. 3. The incubator according to claim 2, further comprising a flow passage, in particular an exhaust gas conduit, which is arranged for conveying exhaust gas from the measuring chamber into a space outside the measuring chamber.

4. 3. The incubator according to claim 2, further comprising a flow path, in particular a return gas conduit, which is arranged to transport exhaust gas from the measurement chamber, preferably through a filter, in particular a HEPA filter, back into the incubator chamber.

5. 3. The incubator of claim 2, wherein the sensor device has a plurality of VOC sensors, and the measurement areas of the VOC sensors, in particular the adsorption surfaces of the VOC sensors, are arranged in contact with the interior space of the measurement chamber.

6. 6. The incubator according to claim 2 or 5, wherein the or the VOC sensor is a MOX sensor and has a heated side, the heated side being in particular arranged respectively outside the measuring chamber.

7. 3. The incubator of claim 2, wherein the measurement chamber has a torus-shaped internal space of a torus-shaped measurement chamber section of the measurement chamber, and the measurement areas of the multiple VOC sensors are arranged along a wall of the torus-shaped measurement chamber section.

8. 3. The incubator according to claim 2, wherein the sensor device is configured as an electronic nose and has an electronic control device as well as a plurality of different VOC sensors, and in particular a purge device by means of which the measuring chamber can be purged with a purge gas.

9. The control device comprises a data processing device with at least one data memory, the data processing device comprising the following steps: i) storing in a data memory a measurement data set comprising measured values, in particular as a function of time, of N>1 of the VOC sensors, the measured values ​​being characteristic of the detected measurement signals of each of the VOC sensors, obtained in the presence of a volume of gas atmosphere originating from the incubator chamber and applied to the measurement range of the VOC sensors, ii) determining first result measurement data from a comparison of the measurement data set with a reference data set, in particular using the differences between the measurement data set and the reference data set, the reference data set in particular comprising reference measurements of N>1 of the VOC sensors recorded as a function of time, the reference measurements being characteristic of the detected measurement signal of each of the VOC sensors recorded in the presence of the purge gas coming from the purge device and applied to the measurement area of ​​the VOC sensor; Optionally: iii) recognising a characteristic data pattern in an outcome measurement dataset comprising said outcome measurement data, said characteristic data pattern being indicative of a VOC, in particular a concentration or amount of said VOC, detected in said ambient gas; 9. The incubator of claim 8, programmed to perform the steps:

10. 10. The incubator of claim 9, wherein step iii) comprises that a classification algorithm determined by machine learning, in particular a neural network, is used to classify the characteristic data patterns.

11. A data processing apparatus having at least one data memory, said data processing apparatus comprising: i) storing in a data memory a test measurement data set comprising test measurements of N>1 VOC sensors, in particular test measurement measurements obtained as a function of time, said test measurements being characteristic of the detected measurement signal of each of said VOC sensors, obtained in the presence of a volume of a pre-known test gas, in particular having a pre-known VOC content in terms of type and / or amount, supplied to the measurement chamber and applied to the measurement area of ​​said VOC sensors, ii) determining second result measurement data from a comparison of the test measurement data set with a reference data set, in particular using the difference between the test measurement data set and a reference data set comprising reference measurement values ​​recorded, in particular as a function of time, of N>1 of the VOC sensors, the reference measurement values ​​being characteristic of the detected measurement signal of each of the VOC sensors, removed from the purge device and recorded in the presence of a purge gas applied to the measurement area of ​​the VOC sensor; 10. The incubator of claim 8, further programmed to perform the step of: iii) storing a second outcome measurement data set including said second outcome measurement data and having a known data pattern characteristic of said test gas.

12. 12. The incubator of claim 11, further comprising a step iv) in which the second outcome measurement data is used as label data to train an adaptive classification algorithm, in particular a neural network, by machine learning, and the adaptive classification algorithm / neural network is subsequently used to classify the measured characteristic data patterns.

13. The incubator of claim 1, further comprising an information output system, in particular a display, a speaker or a data interface with an external data processing device, for outputting information related to the detection, in particular warning information to a user or a monitoring system, in response to the detection of the VOC detected by the sensor device.

14. A laboratory monitoring system for detecting the accumulation of said VOCs in said incubator chamber, in particular for detecting contamination, comprising: At least one incubator according to claim 1; at least one data processing device arranged outside the at least one incubator and in particular in data exchange connection with the at least one incubator, in particular via an intranet or the internet, the data processing device is programmed to obtain measurement data relating to possible contamination of the incubator chamber obtained from the at least one incubator and determined by detection using a sensor device of the incubator, to store said measurement data in a data storage device, in particular to communicate said measurement data to a further device, in particular to a mobile radio device, Laboratory monitoring systems.

15. A method for detecting an accumulation of VOCs in the interior space of the incubator chamber of an incubator according to claim 1, in particular for detecting contamination, comprising: * acquiring measurement data by the sensor device of the incubator, the sensor device having at least one VOC sensor (11) for detecting volatile organic compounds (VOCs), the VOC sensor having the measurement area arranged in fluid connection with the ambient gas of the interior space; determining possible contamination of the gas atmosphere of the interior space by evaluating the measurement data; A method for detecting the accumulation of VOCs comprising:

16. A retrofittable sensor device for detecting VOCs, in particular possible accumulation of contamination, in the gas atmosphere of an internal space of an incubator chamber, the sensor device having at least one VOC sensor (11) for detecting volatile organic compounds (VOCs), the VOC sensor having a measurement area that can be placed in fluid connection with the atmospheric gas of the internal space, the sensor device preferably having a gas conduit that can be placed between the internal space and the measurement area, and preferably having a pump for transporting a predetermined volume of the gas atmosphere of the internal space of the incubator chamber through the gas conduit to the measurement area.

17. 17. An incubator apparatus comprising an incubator with an incubator chamber and a sensor device according to claim 16, the sensor device being arranged on the incubator or in the incubator chamber of the incubator for detecting possible accumulation of VOCs, in particular contamination, in the gas atmosphere of the internal space of the incubator chamber.

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