Controlling system and examination system for microscopic examination of sample and corresponding methods

Abstract

To provide a controlling system for operating an examination system for the microscopic examination of a sample.SOLUTION: A controlling system (140) is configured to: receive a target set value (TS**, CO2**) of at least one examination parameter (TS, CO2), upon user input via a user interface (142); select, based on the received at least one target set value (TS**,CO2**), predefined adjustment set values for at least one incubation environment parameter (RH, CO2) of an incubation mode and at least one microscope parameter; and operate an incubation environment conditioning unit (110) and a microscope (100) based on the selected adjustment set values.SELECTED DRAWING: Figure 1a

Description

[Technical Field]

[0001] The present invention relates substantially to a control system for operating an inspection system configured for microscopic examination of a sample, such an inspection system, a method for microscopic examination, and a method for operating an inspection system. [Background technology]

[0002] In the field of microscopic examination of biological samples such as cells, it is particularly important to maintain the sample under favorable, stress-free environmental conditions for as long as possible. For this purpose, incubators can be used to create a microclimate suited to the sample being examined. Incubators can be distinguished into two types: stage-top incubators and cage incubators.

[0003] Cage incubators are typically mounted on standard microscopes, which can be either upright or inverted, and require a large volume to be incubated because they have a large climate chamber that covers the main parts of the microscope, such as the objective lens revolving nosepiece, the microscope stage containing the sample carrier, and the condenser. Access to the work area for placing or manipulating the sample is located inside the cage incubator and can be accessed through a dedicated opening in the wall of the cage incubator. Due to the large dimensions of the cage incubator, particularly due to these working openings, the cage incubator extends considerably beyond the microscope stand. Therefore, it is impossible to equip a microscope with a cage incubator in a space-saving manner. On the other hand, stage-top incubators surround only the sample itself and are placed on the microscope stage, so the volume to be incubated is small. Although the space requirements of stage-top incubators are minimal, access to the sample is minimized because the sample is enclosed in a sealed box, and this sealed box must be opened, disrupting the incubation atmosphere inside the box. Due to the strict space limitations of stage-top incubator modules, introducing additional equipment for accessing and manipulating the sample is difficult, if not impossible. While cage incubators consume a lot of energy and gas, stage-top incubators have a small, enclosed incubation chamber that includes connected supply conduits for supplying the desired incubation atmosphere. On the other hand, the amount of air exchanged per hour in a cage incubator is usually higher than that of a stage-top incubator, so a stage-top incubator module can quickly equilibrate any disturbances in the incubation atmosphere (e.g., after opening the module) or reach the desired setup.

[0004] The stage top incubator enables precise control of the direct incubation environment surrounding the sample, minimizes the regulated volume, and thereby allows for rapid changes to the incubation environment. However, access to the sample itself is very restricted, and conventionally, stage top solutions add significant complexity and cost to the customer's system. On the other hand, cage incubators are easy to access to the sample, but it takes time to reach the set value of the environmental conditions change and the pre-defined incubation atmosphere.

[0005] When inspecting a sample using such a microscope and incubator, the user needs to set various temperatures and other parameters to specific values in order to achieve the desired sample temperature.

Summary of the Invention

Means for Solving the Problems

[0006] In view of the above situation, it is necessary to improve the incubation solution in microscopy. According to embodiments of the present invention, a control system, an inspection system, a microscopy method, and a method of operating an inspection system having the features of the independent claims are proposed. Advantageous further developments form the subject matter of the dependent claims and the following description.

[0007] Embodiments of the present invention relate to an inspection system configured for microscopic examination of specimens, particularly biological specimens such as cells. It should be noted that the examination of the specimen may also include imaging of such specimen. The inspection system comprises a microscope, an incubation environment conditioning unit connected to the microscope, and a user interface. The user interface preferably comprises at least one of a display and an input device. For example, the user interface may include or be a touch display. Furthermore, the inspection system comprises a control system for operating the inspection system, which is also the subject of embodiments of the present invention. The control system and the inspection system, as well as the corresponding operating methods, will be described together below.

[0008] The microscope comprises, for example, an illumination optical system having a light source and a condenser; a microscope stage (on which a sample is placed); and an imaging optical system having, for example, an objective lens and an image detector. The microscope further comprises a sample chamber configured to receive a sample (preferably, the sample side of the microscope stage is part of such sample chamber); a microscope interface configured to connect an incubation environment conditioning unit to the sample chamber; and an imaging optical system chamber separated from the sample chamber and surrounding the imaging optical system.

[0009] The inspection system configured for microscopic inspection further provides an incubation mode in which the sample chamber is incubated by supplying an incubation atmosphere generated by the incubation environment conditioning unit. This may include supplying a specific gas or humidity to the sample chamber and heating the sample chamber. The sample chamber may be a stage-top chamber or a cage chamber, as described above. Preferably, the microscope is configured to provide both a stage-top chamber and a cage chamber, and the user can select and use one of them when inspecting a sample. Further details of specific types of sample chambers will be provided later.

[0010] The inventors recognize that setting and adjusting the temperature and other parameters of incubators and microscopes is difficult and time-consuming. In a fully equilibrated system, all components of the microscope surrounding the sample, as well as the sample itself, should reach a mutually set temperature. This means that the temperatures of the air above and below the sample, the sample container, the objective lens, and the sample surface must be brought close to each other. Therefore, cage incubators typically include the objective lens and objective lens revolving nosepiece, as well as the bottom side of the sample, within the incubated volume, as described above. In addition, especially when used with a stage-top incubator, several devices (e.g., a silicone pad incorporating heating foil wrapped around the objective lens) are available to introduce and control the precise temperature of the objective lens itself.

[0011] Cage incubators typically include components and volume below the sample plane inside the volume being incubated. However, this type of setup has several drawbacks, as we recognize, namely (a) areas within the incubator assembly that are poorly ventilated, (b) the absence of sensors to check the temperature around the objective lens, and (c) the inability to change the air temperature within the substage compartment without changing the overall temperature setpoint of the system. Because these systems are fully integrated systems, (d) it is not possible to compensate for the introduction of heat into the substage volume by the microscope's electronic components during operation or during changes in the microscope's operating mode.

[0012] A heated collar can be attached to the objective lens itself, which may help partially overcome the aforementioned problem (c). However, such a collar cannot be attached to all types of objective lenses (e.g., motorized objective lenses), and is ultimately under the control of the incubator, not the microscope. The air surrounding the microscope cannot be controlled by such a solution.

[0013] In the existing configuration, the microscope and incubator are two independent systems. The incubator displays the current readings on the microscope user interface and can also receive setting commands from the microscope software, but each system operates and is controlled independently.

[0014] However, a control system of one embodiment of the present invention is configured to perform certain steps to operate the inspection system. These steps include receiving a target setting for at least one inspection parameter, such as sample temperature, upon user input via the user interface, and selecting predefined adjustment setting values ​​for at least one incubation environment parameter of the incubation mode, such as temperature or humidity in the sample chamber, and at least one microscopy parameter, based on the received target setting.

[0015] These predefined adjustment settings are preferably part of one or more datasets, for example, the dataset may take the form of a lookup table containing target settings for inspection parameters that correlate to at least one specific adjustment setting among incubation environment and microscopy parameters. Such specific correlations can be obtained from testing and / or simulation and preferably represent optimal inspection conditions for a sample. Different datasets or lookup tables can be used for different incubation environments and / or microscopy parameters. In other words, the adjustment settings for incubation environment parameters and microscopy parameters are selected from one or more datasets, each dataset containing at least one adjustment setting among incubation environment parameters and microscopy parameters that correlates to a target setting for sample temperature.

[0016] Furthermore, the control system is configured to operate the incubation environment conditioning unit and microscope based on selected (predefined) adjustment setpoints. This includes, for example, operating the heater and pump in the incubation environment conditioning unit and the fan in the microscope to reach the selected adjustment setpoints. This typically takes some time after user input and requires measurement of the current values ​​of these parameters and feedback for closed-loop control.

[0017] Therefore, the idea of ​​one embodiment of the present invention is to integrate a microscope and incubation solution by implementing feedback control between two systems. With a single click in the user interface (which may correlate with the microscope software), the user can change multiple parameters in the incubator and microscope in parallel, for example, by setting the desired temperature of the sample. This allows both systems to work together to perfectly equilibrate the entire inspection system, including the temperatures of the objective lens, sample, sample chamber, and substage volume (imaging optical system chamber).

[0018] In particular, when the user changes the target temperature setting of the sample, the incubator and microscope are forced to utilize various parameter datasets or lookup tables, preferably containing predefined adjustment settings for parameters that have been previously validated by integrated testing.

[0019] As described above, a preferred test parameter for which the user can set a target value is the sample temperature. Furthermore, target values ​​for one or more other or additional test parameters can preferably be set via user input and user interface. These parameters may include the carbon dioxide concentration and oxygen concentration within the sample chamber. Depending on the specific sample and / or test procedure being performed, target values ​​for such test parameters (if provided by the incubation environment conditioning unit) can be used. It should be noted that a further parameter particularly relevant to such sample testing may be the (relative) humidity (concentration of moisture in the air or atmosphere) within the sample chamber. Selecting a target value for this parameter is not an easy task for the user due to its strong dependence on other parameters, and excessively high humidity can cause condensation or evaporation of the sample within the chamber. Therefore, in a preferred embodiment of the present invention, an appropriate humidity as an incubation environment parameter is automatically provided by the incubation environment conditioning unit, either by the user or in response to one or more temperature (adjusted) settings or values ​​already selected from a dataset. Furthermore, it is possible to switch the humidity on and off, meaning the user can choose whether or not to provide a controlled level of relative humidity within the sample chamber.

[0020] Preferably, at least one incubation environment parameter includes at least one of the group consisting of temperature and humidity within the sample chamber. The temperature within the sample chamber is particularly related to the temperature of the air or atmosphere within the sample chamber. Furthermore, the carbon dioxide concentration and / or oxygen concentration within the sample chamber of the incubation environment can be used. The latter can be used as both a test parameter and an incubation environment parameter.

[0021] As described above, adjustment settings for at least one microscope parameter are also selected. Such at least one microscope parameter includes, in particular, the operating speed of the microscope fan configured to ventilate the imaging optical system chamber. Note that the fan operating speed may also include the case where the fan is not operating (speed 0). Depending on the fan, only zero and a specific operating speed may be selectable, or the operating speed settings may differ or be set continuously within a certain range. Alternatively or additionally, such microscope parameters may include at least one of the group of temperatures within the imaging optical system chamber (i.e., the temperature of the air or atmosphere within the imaging optical system chamber) and the temperature of the imaging optical system. Such a fan typically affects both temperatures. These temperatures then affect the sample temperature, in particular when the sample stage is located near the imaging optical system or near an objective lens that is heated by electronic equipment. The sample temperature can be a further microscope parameter, which correlates with the temperature of the immersion medium, if one is used, and the temperature of the immersion medium affects the diffraction index. This diffraction index can then be used to adapt the imaging optical system.

[0022] In summary, these adjustment settings include, in particular, the incubator ambient air temperature settings in cage mode or stage-top mode, as well as dedicated humidity settings. The latter value is specifically intended to prevent condensation or evaporation of the sample or inside the sample chamber at each temperature setting. For this reason, humidity is not used as a test parameter from which the user can select a target setting; rather, humidity is set automatically according to the predefined adjustment settings or values ​​described above. A separate dataset or lookup table may be used for the temperature and humidity inside the sample chamber.

[0023] In addition, further datasets or lookup tables can be used to variably utilize the heat generated by the microscope's electronic components to bring the temperature of the objective lens and the substage volume (within the imaging optical chamber) closer to the sample temperature. Furthermore, such datasets may be of a type other than lookup tables, and for example, characteristic lines, curves, or functions can be used.

[0024] For example, when zebrafish (typical target temperature in the sample: 28°C) or yeast (30°C) are imaged in the imaging system, a fan or fan assembly introduces air from the surrounding room into the imaging optical chamber, and the warm air is expelled from the system. Electron heat is thus expelled from the objective lens, and the objective lens is equilibrated at a temperature very close to the sample temperature. This procedure is applied, for example, from room temperature up to a verified temperature limit in the sample, which ensures that the objective lens temperature, the air temperatures above and below the stage, and the sample temperature exhibit the smallest possible deviations. As a result, the objective lens temperature closely follows the sample temperature within this range.

[0025] However, when performing experiments using the inspection system at temperatures higher than the aforementioned temperature limits, such as cell culture experiments (e.g., at 37°C), the fan or fan assembly is stopped, and electronic components are allowed to introduce additional heat to the objective lens. This brings the temperature of the objective lens closer again to the higher temperature of the sample. This procedure is applied, for example, between room temperature and 45°C.

[0026] Advantageously, the control system is further configured to determine when at least one of at least one inspection parameter, at least one incubation environment parameter, and at least one microscope parameter reaches a value within a predetermined range near its respective selected adjustment setting value, or reaches the value of the selected adjustment setting value, and to indicate to the user via the user interface that the inspection system is ready for inspection. Indicating to the user may include displaying corresponding text on the display, activating a (real or virtual) lamp (such as switching from red to green), etc. It may also be possible to play a sound. This allows the user to do other things while waiting for the inspection system to be ready for use and inspection of the sample.

[0027] A more preferred method for operating the incubation environment conditioning unit and microscope based on selected adjustment settings is when the control system is configured to determine whether at least one of the following has reached a predefined value: the temperature of the sample, the temperature in the sample chamber, the temperature in the imaging optics chamber, and the temperature of the imaging optics. Each predefined value may be a value defined by the respective target setting or selected adjustment setting, or a value within a range (in the sense of a threshold) near the respective target setting or selected adjustment setting.

[0028] It should be noted that each of the temperatures mentioned is either a test parameter, an incubation environment parameter, or a microscopy parameter. Furthermore, each of these temperatures affects the temperature of the sample and the temperature inside the sample chamber, and consequently, the maximum value of the humidity (or concentration of moisture in the atmosphere) inside the sample chamber. For example, the higher the temperature inside the sample chamber, the higher the maximum value (saturation) of humidity (or relative humidity). In addition, the temperature typically affects the evaporation of moisture in the sample.

[0029] Therefore, after each temperature reaches its predetermined value, the incubation environment conditioning unit is activated to begin controlling the humidity within the sample chamber. This prevents condensation of moisture in the sample or elsewhere within the sample chamber during the low-temperature startup phase. Furthermore, it prevents the evaporation of undesirable moisture. It is not necessary to wait while controlling the humidity until the target setpoint or selected adjustment setpoint is reached; rather, since it takes some time for the humidity to rise, humidity control may be started before that. A specific range near the setpoint (threshold) can be determined individually for each situation.

[0030] As described above, the inspection system combines two subsystems: an incubation environment conditioning unit and a microscope. Typically, each of these two subsystems has its own control unit, etc. In a preferred embodiment, the control system comprises a microscope control unit (typically including a processor) configured to operate the microscope based on selected adjustment setpoints for microscope parameters, and at least one incubation control unit (typically including a processor) configured to supply the incubation atmosphere based on selected adjustment setpoints for incubation environment parameters. This means that both control units together form a control system, and essentially each control unit enables processing of its respective parameters, which includes receiving target setpoints and selecting the respective adjustment parameters. For example, the microscope control unit includes at least one dataset for microscope parameters, each with its respective adjustment setpoint, and the incubation control unit includes at least one dataset for incubation environment parameters, each with its respective adjustment setpoint. Therefore, in a preferred embodiment, the selection of predefined adjustment settings for incubation environment parameters can be performed within the incubation control unit, and the selection of predefined adjustment settings for microscope parameters can be performed within the microscope control unit. Receiving a target setting for at least one inspection parameter from the user interface can be done within the microscope control unit (or within the incubation environment control unit).

[0031] However, in another preferred embodiment, the microscope control unit is further configured to receive a target setting for at least one inspection parameter from the user interface, select predefined adjustment setting values ​​for the incubation environment parameters and microscope parameters, and transmit the selected adjustment setting values ​​for the incubation environment parameters to the incubation control unit. Thus, the microscope control unit is used to process user input and operate or execute any necessary software to select appropriate adjustment setting values ​​for all parameters based on the dataset. This also means that the dataset is provided in the microscope control unit, preferably, for example, in the control unit's memory. Thus, the incubation control unit only receives the relevant setting values ​​for the incubation environment parameters and does not need to process any particular decision or selection process. It should be noted that at least one incubation control unit does not necessarily have to be part of the control system.

[0032] The inspection system is preferably configured to display to the user, via the user interface, the current values ​​of at least one inspection parameter, such as sample temperature, and at least one incubation environment parameter. This provides the user with an overview of the current process status. Furthermore, if necessary, the current values ​​of microscope parameters (e.g., fan on or off) can be displayed.

[0033] Advantageously, the inspection system further comprises an atmosphere control module for controlling at least one incubation environment parameter in incubation mode. Such an atmosphere control module can be connected to a control system or incubation control unit, thereby allowing for further adjustment or fine-tuning of the incubation atmosphere. For this purpose, a sensor may be provided within the atmosphere control module, or at least a sensor signal may be provided to the atmosphere control module, the sensor signal representing the value of at least one incubation environment parameter. If the actual value of such parameter deviates from the set value of that parameter, the atmosphere control module can adjust / readjust each parameter.

[0034] For this purpose, it is advantageous for the atmosphere control module to communicate with the incubation control unit and / or the pump control unit for the incubation mode. In this embodiment, if the temperature or humidity of the incubation atmosphere deviates from a corresponding setpoint, the atmosphere control module can send a request to the corresponding (pump) control unit to adjust / re-adjust the temperature or humidity to the correct setpoint. Alternatively, the atmosphere control module may be provided with corresponding means for such adjustment / re-adjustment. For example, the atmosphere control module may be provided with at least one of a heater / cooler and a humidifier to adjust the temperature and / or humidity of the incubation atmosphere independently, without communicating with the corresponding (pump) control unit, once an adjustment setpoint is provided.

[0035] As already mentioned, in a preferred embodiment, the inspection system is configured to provide or supply an incubation atmosphere to two different types of sample chambers. For this purpose, the microscope further comprises a microscope housing surrounding illumination optics, a microscope stage, and imaging optics. Furthermore, the microscope comprises an integrated sample chamber located within the microscope housing and formed by a separation housing section within the microscope housing. The imaging optics chamber is located within the microscope housing and separated from the sample chamber. Thus, the first type of sample chamber is a sample chamber integrated into the microscope housing. This type of sample chamber is also referred to as a cage chamber, as well as a cage incubator that provides a sample chamber.

[0036] A second type of sample chamber is located within the integrated sample chamber. This second type of sample chamber is also referred to as a stage-top chamber, as is the case with stage-top incubators that provide sample chambers. Furthermore, the housing section includes the microscope interface configured to connect an incubation environment conditioning unit to the integrated sample chamber and / or a stage-top sample chamber located within the integrated sample chamber. It should be noted that such a second type of sample chamber is typically not fixed to the microscope or integrated sample chamber, but can be located within them as required.

[0037] In this configuration, the inspection system provides individual incubation modes for each sample chamber. Specifically, the inspection system provides a first incubation mode and a second incubation mode, in which the integrated sample chamber is incubated by supplying a first incubation atmosphere by the incubation environment conditioning unit, and in the second incubation mode, the stage top chamber is incubated by supplying a second incubation atmosphere by the incubation environment conditioning unit. Furthermore, the control system is configured to operate the incubation environment conditioning unit and the microscope based on selected adjustment settings for one of the selected incubation modes, either the first or the second. It should be noted that this may require different datasets for the two incubation modes, and that these datasets correlate adjustment settings for one or more incubation environment parameters and / or microscope parameters that correlate to a target setting for at least one inspection parameter.

[0038] This provides customers with two incubation solutions implemented within the same testing system. In the first incubation mode, the volume to be incubated is reduced to the volume of the isolation housing section within the microscope housing, and this volume is already minimized as it is specifically designed for the needs of each microscope and intended application. The sample chamber has enough space to perform all the necessary sample manipulations required by the application, leaving ample space for any additional necessary equipment. Furthermore, this system allows the user to utilize a stage-top incubator without switching to a different system. This preferred embodiment combines the stage-top and sample chamber incubators into a single system, sharing common components and achieving reproducible incubation conditions with respect to temperature uniformity, heating stages, etc. For both types of sample chambers or incubation modes, a one-click solution is available for setting various parameters.

[0039] In a further embodiment of the present invention, a method is provided for microscopic examination of a sample using the inspection system described above. Such a method includes the steps of: providing a sample in a sample chamber (depending on the type of inspection system, this may include selecting one of two different sample chambers); providing a target setting value for at least one inspection parameter upon user input via the user interface; and examining the sample by microscope after reaching defined thresholds for predefined adjustment setting values ​​for at least one incubation environment parameter of the incubation mode and at least one microscopic parameter. These defined thresholds may correspond to or slightly differ from values ​​set by the adjustment setting values. In this regard, see also the above view addressing when the inspection system is ready for inspection.

[0040] The adjustment settings for incubation environment parameters and microscopy parameters are selected from one or more datasets, each dataset containing one or more adjustment settings for incubation environment parameters and / or microscopy parameters that correlate to a target setting for at least one test parameter.

[0041] In a further embodiment of the present invention, a method is provided for operating an inspection system configured for microscopic inspection of a sample, the inspection system comprising a microscope, an incubation environment conditioning unit connected to the microscope, and a user interface. The microscope comprises an illumination optical system, a microscope stage, an imaging optical system, a sample chamber configured to receive a sample, a microscope interface configured to connect the incubation environment conditioning unit to the sample chamber, and an imaging optical system chamber separated from the sample chamber and surrounding the imaging optical system. Furthermore, the inspection system provides an incubation mode in which the sample chamber is incubated by supplying an incubation atmosphere generated by the incubation environment conditioning unit.

[0042] The method includes the steps of: receiving a target setting value for at least one inspection parameter, preferably including at least the target temperature of the sample, when a user input is received via the user interface; selecting predefined adjustment setting values ​​for at least one incubation environment parameter and at least one microscope parameter of the incubation mode based on the received target setting value for at least one inspection parameter; and operating the incubation environment conditioning unit and microscope based on the selected adjustment setting values. For further preferred embodiments of the inspection system, please refer to the views described herein as applied accordingly.

[0043] For any further details of the method, preferred embodiments, and advantages, including aspects of the method, please also refer to the views described herein as applied accordingly.

[0044] The present invention also relates to a computer program having program code for performing a method according to the present invention when the computer program is executed on one or more processors or a control system according to the present invention.

[0045] Further advantages and embodiments of the present invention will become apparent from the description and accompanying drawings.

[0046] It should be noted that the features described above and those further described below can be used not only in the combinations shown, but also in further combinations or individually, without departing from the scope of the present invention. [Brief explanation of the drawing]

[0047] [Figure 1a] This figure schematically shows a perspective view of an inspection system according to a preferred embodiment of the present invention. [Figure 1b] This figure schematically illustrates an inspection system according to a more preferred embodiment of the present invention. [Figure 2] This figure schematically illustrates an inspection system and flowchart according to a more preferred embodiment of the present invention, for explaining the various steps of operation. [Figure 3a] This figure schematically illustrates various steps for operating an inspection system according to a more preferred embodiment of the present invention. [Figure 3b] This figure schematically illustrates various steps for operating an inspection system according to a more preferred embodiment of the present invention. [Figure 4a] This figure schematically illustrates an inspection system according to a more preferred embodiment of the present invention in two different operating states. [Figure 4b] This figure schematically illustrates an inspection system according to a more preferred embodiment of the present invention in two different operating states. [Modes for carrying out the invention]

[0048] Figure 1a schematically shows, in a perspective view, an inspection system 130 for microscopic inspection of a sample 120 according to a preferred embodiment of the present invention. The inspection system 130 comprises a microscope 100, an incubation environment conditioning unit 110, a control system 140 including, for example, a PC 146, and a user interface 142, which comprises, for example, a display or display screen, a keyboard, and a computer mouse for providing the user interface to the user.

[0049] The control system 140 comprises a microscope control unit 214, an incubation control unit 212, and, for example, a PC 146, the PC being connected to a user interface. The functions of the PC can also be integrated into, for example, the microscope control unit 214. The user interface means may alternatively include, for example, a touchscreen.

[0050] Microscope 100 is used for microscopic examination of a sample 120 placed on a microscope stage 116. The microscope housing 102 surrounds the illumination optical system 118, the microscope stage 116, and the imaging optical system 124. An integrated sample chamber 106 is located within the microscope housing 102 and is formed by a separate housing section 104 within the microscope housing 102. The housing section 104 is equipped with a hinged lid 109, which provides direct access to the microscope stage 116 for placing the sample 120 in the sample chamber 106 onto the microscope stage 116, and for changing and / or manipulating the sample 120 when the lid is open.

[0051] The embodiment shown in Figure 1a is a back-transmitted light microscope 100, in which a transmitted light illumination optical system 118 is located within a housing section 104, and an imaging optical system 124 is located below the microscope stage 116 in a second housing section, forming an imaging optical system chamber 122. The imaging optical system 124 typically includes a microscope objective lens and an image detector as its main components. The image detector usually includes a camera that generates a microscope image, which is typically displayed on a display screen of a user interface 142 outside the microscope housing 102.

[0052] The structure of the microscope housing section 104 allows for the formation of a dedicated sample chamber 106 after the lid 109 is closed. This sample chamber 106 provides a preferred sealed space that can be incubated, allowing biological samples 120, such as cells, to be kept under good, stress-free environmental conditions during microscopic examination / imaging. For this purpose, the housing section 104 includes an interface 108 for connecting an external incubation environment conditioning unit 110 to the sample chamber 106. The interface 108 is configured to provide a connection between the incubation environment conditioning unit 110 and the sample chamber 106, so that the conditioning unit 110 can control the environmental conditions within the sample chamber 106 when connected to the interface 108. This configuration implements a first incubation mode ("sample chamber incubation").

[0053] In the illustrated embodiment, the interface 108, as part of the housing section 104, comprises two openings 112 on the rear of the housing section 104, each opening 112 configured to receive a conduit 114. The incubation atmosphere can be introduced into the sample chamber 106 through at least one of the conduits 114. Depending on the amount of leakage from the sample chamber 106, a portion of the incubation atmosphere can be released from the sample chamber 106. Conversely, a portion of the incubation atmosphere can be withdrawn from the sample chamber 106 through another conduit 114.

[0054] A suitable incubation atmosphere includes, for example, air containing a predefined amount of H2O (water or water vapor, relative humidity) and a predefined amount of CO2 (carbon dioxide). It is also desirable to conduct hypoxic experiments in an oxygen-deficient atmosphere. For further details regarding specific parameters and appropriate or preferred ranges, please refer to the diagram description below.

[0055] It should be noted that the control of relevant parameters (incubation environment parameters, e.g., sample chamber temperature, humidity, carbon dioxide concentration, oxygen concentration; microscope parameters, e.g., fan speed) is performed automatically by the control system 140, and the user sets the target value for the sample temperature as an inspection parameter, for example.

[0056] To control the above parameters, it is preferable to place the sensor in or on at least one of the vicinity of the sample 120 in the conduit 114, the sample chamber 106, and the microscope stage 116. In a preferred embodiment, at least a portion of the sensor is incorporated into the conduit 114 for supplying the incubation atmosphere to the sample chamber 106.

[0057] As shown in Figure 1a, the housing section 104 has a lower boundary by the work surface 107, which includes the upper side of the microscope stage, in other words, the tabletop of the microscope stage. This structure provides user-friendly access to the work area for positioning and manipulating the sample 120. On the other side, the housing section is bounded by the inside of the lid 109 and the back of the housing section 104 itself.

[0058] To extend the lifespan of the imaging optical system 124, and when using immersion objective lenses, for example, the imaging optical system chamber 122 is air-conditioned and / or temperature-controlled. For this purpose, a fan 126 is provided for ventilating the imaging optical system chamber 122, which can be operated or controlled by the control system 140, or in particular by the microscope control unit 214 as part thereof.

[0059] The microscope control unit 214 further controls functional components of the microscope 100, such as the illumination optical system 118, microscope stage 116, and imaging optical system 124, to control the microscopic examination / imaging of the sample 120. Typically, the user interface 142 provides a graphical user interface (GUI) displayed on the display screen for user-friendly operation of the microscope 100.

[0060] The control system 140 is further configured to control the operation of the incubation environment conditioning unit 110 when the conditioning unit 110 is connected to interface 108, in particular via the incubation control unit 212 provided for this purpose. Cables and lines for communication between PC 146 and / or microscope control unit 214 and incubation control unit 212 can be routed through one or more of the above-mentioned openings / conduits of interface 108.

[0061] As shown in Figure 1a, the default configuration is the first incubation mode, which in this embodiment is the sample chamber incubation mode. The incubation environment conditioning unit 110 includes the incubation control unit 212 shown in Figure 1a. Inside the housing section 104, on its rear side, is an atmosphere control module interface to which the atmosphere control module 216 is connected, as shown in Figure 1a.

[0062] The sensors described above for detecting one or more of the incubation atmosphere parameters are preferably located within the sample chamber 106, particularly within or on the atmosphere control module 216. The atmosphere control module 216 is connected to the incubation environment conditioning unit 110 via a communication line. In this way, in response to sensor signals corresponding to parameter values, the first atmosphere control module 216, together with the incubation control unit 212, can provide feedback control to set a first group of parameters of the first incubation atmosphere to desired setpoints. This process will be further described with reference to the following figures.

[0063] Furthermore, the stage-top sample chamber 206 is indicated by a dashed line. Such a stage-top (or table-top) sample chamber will be placed within the integrated sample chamber 106, and connections to the opening 112 and / or conduit 114 can also be established to provide the respective incubation environment within the smaller stage-top sample chamber 206. The user can select which sample chamber to use, and to use the table-top sample chamber 206, it must be placed within the integrated sample chamber 106.

[0064] Figure 1b schematically illustrates an inspection system 130 according to the present invention in a further preferred embodiment. The inspection system 130 may correspond to that shown in Figure 1a. However, Figure 1b specifically shows the components and parameters of the inspection system 130, which are particularly relevant within embodiments of the present invention. Note that similar components and parameters are given the same reference numerals throughout the drawings.

[0065] The left side of Figure 1b shows the user interface 142, where the sample temperature T is used as an inspection parameter. S The symbol is displayed, and next to it, the target temperature setting T for this sample. S ** The interface displays input fields. The user can increase or decrease the target setting value for that temperature by, for example, clicking each soft button. Furthermore, the user interface 142 displays the temperature in the sample chamber, the carbon dioxide concentration (CO2) as a test parameter, and next to it, the target setting value (CO2) for this concentration. ** The system displays fields for inputting values. Users can increase or decrease the target value for each concentration by, for example, clicking the respective soft buttons. Note that typically the most relevant test parameter is the sample temperature, and changes to or use of carbon dioxide concentration may be invalid. In the following, carbon dioxide concentration is not considered (or is considered invalid).

[0066] Furthermore, the user interface 142 displays a symbol for the (relative) humidity RH in the sample chamber. The humidity is an incubation parameter that is automatically set, not an inspection parameter. The user cannot change the set value. Therefore, only the current value may be displayed, and it is also possible to switch on and off the use of humidity (moisture in the sample chamber). Furthermore, the user interface 142 displays a colored symbol 144 representing a (virtual) lamp. Such a lamp can, for example, switch from red to green when the inspection can be started. This will be described in detail later.

[0067] The right side of FIG. 1b very schematically shows the sample chamber 106 and the imaging optical system chamber 122. In particular, the illumination optical system 118, the microscope stage 116, the sample 120, and the imaging optical system 124 are shown. Note that the imaging optical system, as an example, includes a motorized objective lens on a turret.

[0068] FIG. 2 shows an inspection system 130 and a flow diagram according to a further preferred embodiment of the present invention, and explains various steps for operating the inspection system based thereon. In particular, FIG. 2 shows a sample chamber 106, an imaging optical system chamber 122, an illumination optical system 118, a microscope stage 116, a sample 120, and an imaging optical system 124 similar to those in FIG. 1b. Furthermore, an incubation control unit 212 and a microscope control unit 214 (both of which may be part of the control system) are schematically shown.

[0069] In the first step S1, the user can set a target set value T for the temperature T of the sample via the user interface as described above with respect to FIG. 1b. The control system, particularly the microscope control unit 214 and / or the incubation control unit 212, receives this target set value T. S to the target set value T S ** . The control system, particularly the microscope control unit 214 and / or the incubation control unit 212, receives this target set value T S ** .

[0070] In a further step S2, the control system receives the target setting value T. S ** Based on this, a predefined adjustment set value RH for the (relative) humidity RH in the sample chamber. * And the temperature T of the sample chamber ch Predefined adjustment setting T for ch * Select and . These two parameters are incubation environment parameters because they refer to the sample chamber 106 where the incubation environment is provided. In addition, a predefined adjustment set value v for the operating speed v of the fan 226 in the imaging optical system chamber. * This is selected. This parameter is a microscope parameter because it refers to the components of the microscope and the corresponding imaging optical chamber 122 in which the fan is located. The method for selecting such adjustment settings based on the target setting is described below with reference to Figure 3a.

[0071] Next, in a further step S3, the incubation environment conditioning unit 110 and the microscope 100 use the control system or microscope control unit 214 and / or incubation control unit 212 respectively to control three parameters RH, T ch and v are the respective adjustment setting values ​​RH selected earlier. * , T ch * and v * It is manipulated to reach a certain point.

[0072] In the imaging optical system chamber 122, this refers to the temperature T inside the imaging optical system chamber. sub and the temperature T of the imaging optical system (equipped with an objective lens) obj However, this means that it changes due to the heat generated by the operation of the imaging optical system (e.g., including the motor for the imaging detector and motorized objective lens, and other electronic components). Depending on the fan operating speed v, the effect of the heat generated by the electronic components will be greater or smaller, but for a more detailed explanation, please refer to Figures 4a and 4b. As mentioned above, temperature Tsub and T obj (and sample temperature T S These can also be used as microscope parameters, each with its own adjustment setting value.

[0073] It should be noted that controlling these parameters to achieve each adjustment setpoint typically involves repeatedly measuring (or otherwise determining) the current values ​​of these parameters, feeding these current values ​​back into the control system, and changing the operating variables as needed. It should be noted that this can be accomplished by typical closed-loop control. In this regard, the atmosphere control module 216 and the sensors described above can be used.

[0074] After a certain period of time, the adjustment setpoint is reached as shown in step S5, and therefore the target setpoint T for the sample temperature is reached. S ** It also reaches that point.

[0075] Figures 3a and 3b schematically illustrate the various steps for operating the inspection system according to a more preferred embodiment of the present invention, particularly with respect to Figure 2. Furthermore, a user interface 142 displaying all the elements shown in Figure 1 is shown on the right side of each of Figures 3a and 3b.

[0076] The left side of Figure 3a shows dataset 300, where the temperature T of the sample chamber is measured. ch The adjustment settings for humidity RH (incubation environment parameter) and fan operating speed v (microscope parameter) within the sample chamber are controlled by the sample temperature T. SThe (inspection parameters) are correlated with target setting values. Specifically, the graph curves show a dataset of 300 for each of these parameters, and the parameter values ​​are defined by the vertical axis. Note that the specific values ​​or paths of the lines are not relevant to the description of the present invention. Possible physical units for the parameters include °C (Celsius) for temperature, % (percentage) for humidity, and rpm (revolutions per minute) for fan speed (the latter can also be expressed as on / off as a simple example).

[0077] Next, we will explain how to select adjustment settings based on the target setting. As mentioned above, the user selects the target setting T. S ** The desired temperature of the sample can be selected. In the specific dataset 300 shown in the figure, the corresponding adjustment setting value RH * , T ch * and v * is, T S The curve represents the target value T. S ** It can be determined by drawing a perpendicular line passing through the point where it intersects. The adjustment setting value RH obtained in this way * , T ch * , v * The next option is selected, and the system operates based on these options.

[0078] It should be noted that graphical representation of dataset 300 is a preferred method primarily for showing the correlation between various parameters and their setpoints. A typical way to implement such a dataset in a control system is, for example, as a set of multiple values, each set containing one value for each parameter. This makes it possible, for example, to select a set in which the sample temperature value matches a given target setpoint.

[0079] The left side of Figure 3b shows the humidity RH inside the sample chamber and the temperature T inside the sample chamber over time t, according to a preferred embodiment of the present invention. ch and the temperature T of the objective lens objThis shows the change. When the incubation environment conditioning unit and microscope start operating (see the far left of the figure), the temperature T inside the sample chamber changes. ch and the temperature T of the objective lens obj It increases over time, reaching its final value. These final values ​​are determined by the temperature T inside the sample chamber. ch For the selected adjustment setting value T ch * This corresponds to the objective lens being in very close proximity to the sample 120 and the sample chamber 106, so the temperature of the objective lens T obj The final value is the temperature T inside the sample chamber. ch Please note that this is very close to the final value.

[0080] As can be seen from the figure, humidity RH decreases as operation begins. This is because the change or control of humidity RH is not started together with other parameters. Rather, humidity is not actively changed from the beginning. However, the temperature T inside the sample chamber ch The increase in humidity results in only a slight decrease in humidity. The reason for not actively increasing humidity from the start is that if the humidity becomes too high at low ambient temperatures, moisture may condense on the sample or other components within the sample chamber. At low temperatures, the maximum relative humidity in the air is lower than at high temperatures.

[0081] At time point t1, indicated by the black star, the temperature inside the sample chamber T ch (Threshold) T ch It reached '. This is considered a sufficiently high temperature so that condensation does not occur even if the humidity RH is increased. Therefore, the control system sets the selected adjustment setpoint RH. * To achieve this, the incubation environment conditioning unit 110 is started to increase the humidity RH.

[0082] Similarly, at time point t2, indicated by the hollow star, the temperature inside the sample chamber T ch The selected adjustment setting value T ch *Once reached, the humidity RH will be set to the respective selected adjustment setting value RH. * The value RH' has reached a value slightly below the target value. These conditions are considered sufficient to begin testing the sample once the sample temperature reaches the target setpoint, for example. This is indicated to the user via the user interface 142, for example, by the color of symbol 144 (a virtual lamp) changing from red to green.

[0083] Note that, depending on the situation, the point at which the inspection system indicates it is ready for inspection can also be set to when the humidity (RH) reaches the selected adjustment setpoint. Furthermore, other parameters may be included.

[0084] Figures 4a and 4b show the inspection system 130 according to a more preferred embodiment of the present invention in two different operating states. The inspection system 130 corresponds to the one shown in Figure 2. As described with respect to step S2 in Figure 2, the fan operating speed v is set to a selected adjustment setting, whether or not it is a microscope parameter.

[0085] Figure 4a shows the situation where the operating speed is set to 0, i.e., the fan 128 is not operating, and therefore no ventilation occurs, and the heat generated from the electronic component 128 of the imaging optical system 124 (or other heat sources in the imaging optical system chamber 122) is not disturbed. This is indicated by a long arrow starting from component 128. As a result, the imaging optical system 124, in particular the objective lens, is heated, and the temperature of the objective lens rises to a relatively high value. Note that typically the objective lens is thermally and optically coupled to the microscope stage (sample carrier) via the immersion medium. Since most of the heat for heating the sample is introduced through the incubation atmosphere, if the respective temperatures are too low, the heat from the sample flows to the objective lens (and imaging optical system chamber). Therefore, the heat generated by the electronic component 128 is used to introduce heat to the objective lens and imaging optical system chamber. The sample chamber is heated in parallel by the incubation unit. The inspection system reaches an equilibrium state in which the temperature of the sample, the temperature of the objective lens, and the temperature of the air below and above the sample plane are nearly identical, especially at higher temperatures. This is preferable when the target temperature of the sample is high (typically around 37°C), for example, when performing cell culture experiments.

[0086] Figure 4b shows a situation where the operating speed is set to a specific value higher than 0, i.e., the fan 128 is operating, and therefore the imaging optical system chamber is ventilated, and the electronic components 128 of the imaging optical system 124 (or other heat sources in the imaging optical system chamber 122) are actively cooled, thereby reducing the heat generated and allowing warm air to be expelled to the outside of the system. This is indicated by a short arrow starting from component 128. As a result, the imaging optical system chamber 122 and the imaging optical system 124, particularly the objective lens, are not heated as much as when the fan is not operating, the temperature of the objective lens does not rise, or at least rises less than when the fan is not operating, the temperature reaches a relatively low value, and the objective lens introduces only minimal heat to the sample, if any. The sample chamber is heated very slightly in parallel by the incubation unit. Thus, the inspection system reaches an equilibrium state of operation, in which the temperature of the sample, the objective lens, and the air temperatures below and above the sample plane are nearly identical at lower temperatures. This is preferable when the target temperature of the sample is low, such as when required for zebrafish (e.g., 28°C) and yeast (e.g., 30°C).

[0087] Note that, depending on the fan's functionality, various operating speeds may be used for different target temperature settings for the sample. However, it is also possible to use a simple fan with only on and off modes.

[0088] In summary, the idea behind one embodiment of the present invention is to integrate a microscope and incubation solution by implementing feedback control between two systems. This provides the user with a one-click solution, for example, where the microscope software changes multiple parameters in parallel in both the incubator and the microscope. This allows both systems to work together to perfectly equilibrate the temperatures of the objective lens, sample, sample chamber, and imaging optical system chamber (substage volume). In particular, the user does not need to pay attention to anything other than the inspection parameters. In a preferred embodiment, the only value the user needs to provide is the desired sample temperature. The remaining parameters are automatically set to optimal values.

[0089] As used herein, the term "and / or" includes all possible combinations of one or more of the related items and may be abbreviated as " / ".

[0090] While several embodiments have been described in the context of the apparatus, it is clear that these embodiments also represent descriptions of the corresponding methods, where blocks or apparatus correspond to steps or features of steps. Similarly, embodiments described in the context of steps also represent descriptions of the corresponding blocks, items, or features of the corresponding apparatus.

[0091] Some embodiments relate to a microscope that includes a system such as those described in relation to one or more of the figures from Figures 1a to 4b. Optionally, the microscope may be part of a system such as those described in relation to one or more of the figures from Figures 1a to 4b. Figure 1a shows a schematic diagram of a system 130 configured to carry out the methods described herein. The system 130 includes a microscope 100 and a computer (control) system 140. The microscope 100 is configured to take images and is connected to the computer system 140. The computer system 140 is configured to carry out at least some of the methods described herein. The computer system 140 may be configured to run machine learning algorithms. The computer system 140 and the microscope 100 may be separate entities or may be integrated within a common housing. The computer system 140 may be part of the central processing system of the microscope 100, and / or the computer system 140 may be part of a dependent component of the microscope 100, such as a sensor, actor, camera, or illumination unit of the microscope 100.

[0092] The computer system 140 may be a local computer device (e.g., a personal computer, laptop, tablet computer, or mobile phone) comprising one or more processors and one or more storage devices, or it may be a distributed computer system (e.g., a cloud computing system comprising one or more processors and one or more storage devices distributed to various locations such as local clients and / or one or more remote server farms and / or data centers). The computer system 140 may include any circuit or combination of circuits. In one embodiment, the computer system 140 may include one or more processors, which can be of any kind. As used herein, the processor may be intended to be any kind of computing circuit, such as a microprocessor for a microscope or microscopic component (e.g., a camera), a microcontroller, a composite instruction set computing (CISC) microprocessor, a reduced instruction set computing (RISC) microprocessor, a very long instruction word (VLIW) microprocessor, a graphics processor, a digital signal processor (DSP), a multicore processor, a field-programmable gate array (FPGA), or any other kind of processor or processing circuit. Other types of circuits that may be included in the computer system 140 may be custom circuits, application-specific integrated circuits (ASICs), etc., such as one or more circuits (communication circuits, etc.) used in wireless devices such as mobile phones, tablet computers, laptop computers, two-way radios, and similar electronic systems. The computer system 140 may also include one or more storage devices that may include one or more memory elements suitable for a particular application, such as main memory in the form of random access memory (RAM), one or more hard drives and / or one or more drives that handle removable media such as compact discs (CDs), flash memory cards, digital video discs (DVDs), etc.The computer system 140 may also include a display device, one or more speakers and a controller which may include a keyboard and / or mouse, trackball, touchscreen, voice recognition device, or any other device which enables the user of the system to input information into and receive information from the computer system 140.

[0093] Some or all of the steps may be performed by a hardware device (or by using a hardware device), such as a processor, microprocessor, programmable computer, or electronic circuit. In some embodiments, one or more of the most critical steps may be performed by such a device.

[0094] Depending on certain implementation requirements, embodiments of the present invention may be implemented in hardware or software. This implementation is feasible using a non-transient recording medium, which is a digital recording medium, etc., that stores electronically readable control signals and cooperates (or can cooperate) with a programmable computer system to carry out each method. Examples include floppy disks, DVDs, Blu-rays, CDs, ROMs, PROMs and EPROMs, EEPROMs, or FLASH memory. Thus, the digital recording medium may be computer-readable.

[0095] Some embodiments of the present invention include a data carrier having electronically readable control signals that can cooperate with a programmable computer system so as to carry out any of the methods described herein.

[0096] Generally, embodiments of the present invention can be implemented as a computer program product comprising program code, which operates to perform one of the methods when the computer program product is executed on a computer. This program code may be stored, for example, on a machine-readable carrier.

[0097] Another embodiment includes a computer program stored in a machine-readable carrier for carrying out any of the methods described herein.

[0098] Therefore, in other words, embodiments of the present invention are computer programs having program code for carrying out any of the methods described herein when the computer program is executed on a computer.

[0099] Accordingly, another embodiment of the present invention is a recording medium (or data carrier or computer-readable medium) containing a stored computer program for carrying out any of the methods described herein when executed by a processor. The data carrier, digital recording medium, or recording medium is typically tangible and / or non-transient. Another embodiment of the present invention is an apparatus, such as those described herein, comprising a processor and a recording medium.

[0100] Therefore, another embodiment of the present invention is a data stream or signal sequence representing a computer program for carrying out any of the methods described herein. The data stream or signal sequence may be configured to be transmitted, for example, over a data communication connection, such as the Internet.

[0101] Another embodiment includes processing means, for example, a computer or programmable logic device configured or adapted to carry out any of the methods described herein.

[0102] Another embodiment includes a computer having an installed computer program for carrying out any of the methods described herein.

[0103] Another embodiment of the present invention includes an apparatus or system configured to transfer (e.g., electronically or optically) a computer program for carrying out any of the methods described herein to a receiver. The receiver may be, for example, a computer, a mobile device, a storage device, etc. The apparatus or system may include, for example, a file server for transferring the computer program to the receiver.

[0104] In some embodiments, a programmable logic device (e.g., a field-programmable gate array) may be used to perform some or all of the functions of the methods described herein. In some embodiments, the field-programmable gate array may cooperate with a microprocessor to carry out any of the methods described herein. Generally, the methods are advantageously carried out by any hardware device. [Explanation of Symbols]

[0105] 100 Microscopes 102 Microscope Housing 104 Separation Housing Section 106 Sample Chamber 107 Work surface 108 Microscope Interface 109 Lid 110 Incubation Environment Conditioning Unit 112 Opening 114 Conduit 116 Microscope Stages 118 Illumination optical system 120 samples 122 Imaging optical system chamber 124 Imaging Optical System 126 Fans 128 Electronic Components 130 Inspection Systems 140 Control Systems 142 User Interface 144 Symbols on the User Interface 146 PC 206 Stage Top Chamber 212 Incubation Control Unit 214 Microscope Control Unit 216 Atmosphere control module T S Sample temperature T ch Temperature of the sample chamber T obj objective lens temperature T sub Temperature inside the imaging optical system chamber Humidity inside the RH sample chamber CO2 (carbon dioxide concentration) T S ** CO2 ** Target setting T ch * RH * Adjustment setting T ch ',RH' value t1, t2 hours

Claims

1. A control system (140) for operating an inspection system (130) configured for microscopic inspection of a sample (120), the inspection system (130) comprising a microscope (100), an incubation environmental conditioning unit (110) connected to the microscope (100), and a user interface (142); The microscope (100) comprises illumination optics (118), a microscope stage (116), imaging optics (124), a sample chamber (106) configured to receive the sample (120), a microscope interface (108) configured to connect the incubation environmental conditioning unit (110) to the sample chamber (106), and an imaging optics chamber (122) separated from the sample chamber (106) and surrounding the imaging optics (124); the inspection system (130) configured for microscopy provides an incubation mode in which the sample chamber (106) is incubated by the supply of an incubation atmosphere generated by the incubation environmental conditioning unit (110); The control system (140) Upon user input via the user interface (142), at least one inspection parameter (T Ｓ , CO ２ ) target set value (T Ｓ ＊＊ , CO ２ ＊＊ ) (S1); and At least one of the received target set values ​​(T Ｓ ＊＊ , CO ２ ＊＊ ) based on at least one incubation environment parameter (T ｃｈ , RH, CO ２ ) and at least one microscope parameter (v,T ｏｂｊ , T ｓｕｂ ) with a predefined adjustment setting (T ｃｈ ＊ , R.H. ＊ , v ＊ ) (S2); and operating (S3) the incubation environment conditioning unit (110) and the microscope (100) based on the selected adjustment setting value; 4. The method of claim 3, A control system (140).

2. The target set point of the at least one inspection parameter is at least a target temperature (T Ｓ ＊＊ ), The control system (140) of claim 1.

3. The at least one incubation environmental parameter is the temperature in the sample chamber (T ｃｈ ) and humidity (RH) in the sample chamber; The control system (140) of claim 1.

4. The control system (140) is further configured to automatically provide a value of the humidity (RH) in the sample chamber, the value being related to the temperature (T Ｓ ), the temperature in the sample chamber (T ｃｈ ), the temperature in the imaging optical chamber (T ｓｕｂ ) and the temperature of the imaging optical system (T ｏｂｊ ) depending on the selected or chosen value of at least one of The control system (140) of claim 3.

5. The at least one incubation environment parameter further includes at least one of a group consisting of a carbon dioxide (CO ２ ) concentration in the sample chamber and an oxygen concentration in the sample chamber. The control system (140) of claim 3.

6. The at least one microscope parameter may include an operating speed (v) of a fan (126) configured to ventilate the imaging optics chamber (122) of the microscope (100) and a temperature (T) within the imaging optics chamber. ｓｕｂ ), the sample temperature, and the temperature of the imaging optical system (T ｏｂｊ ) and at least one of the groups The control system (140) of claim 1.

7. The at least one incubation environmental parameter includes humidity (RH) in the sample chamber and is adjusted to the selected adjustment set point (T ｃｈ ＊ , R.H. ＊ , v ＊ ) operating the incubation environment conditioning unit (110) and the microscope (100) based on the The temperature of the sample (T Ｓ ), the temperature in the sample chamber (T ｃｈ ), the temperature in the imaging optical chamber (T ｓｕｂ ) and the temperature of the imaging optical system (T ｏｂｊ ) are at least one of the respective predefined values ​​(T ｃｈ determining whether a After each temperature reaches a predetermined value, start the operation of the incubation environment conditioning unit (110) to control the humidity (RH) in the sample chamber. Including, Each of the predefined values ​​may be a value defined by each of the target set values ​​or the selected adjustment set values, or a value defined by each of the target set values ​​or the selected adjustment set values ​​(T ｃｈ ＊ ) in the range of neighborhood (T ｃｈ ') The control system (140) of claim 3.

8. The control system (140) At least one of the group of the at least one inspection parameter, the at least one incubation environment parameter, and the at least one microscope parameter reaches a value (RH' within a predetermined range in the vicinity of the selected adjustment set value (RH ＊ ), or when reaching the value of the selected adjustment set value (T ｃｈ ＊ ), and determining the time point; indicating to a user (S5) via the user interface (142) that the inspection system (130) is ready for inspection; and further configured to: The control system (140) of claim 1.

9. The at least one test parameter may be a carbon dioxide concentration (CO ２ ) and an oxygen concentration in the sample chamber; The control system (140) of claim 1.

10. The adjustment settings (T Ｓ ＊＊ , R.H. ＊ , T ｃｈ ＊ , v ＊ ) is selected from one or more data sets (300), each data set including adjustment settings of one or more of the group of incubation environment parameters and microscope parameters that correlate to a target setting of the at least one inspection parameter; The control system (140) of claim 1.

11. The control system includes: The selected adjustment setting value (T ｃｈ ＊ , R.H. ＊ at least one incubation control unit (212) configured to provide said incubation atmosphere based on The selected adjustment setting for the microscope parameter (v ＊ a microscope control unit (214) configured to operate the microscope based on the Equipped with The control system of claim 1 .

12. The microscope control unit (214) The at least one inspection parameter (T Ｓ ) the target set value (T Ｓ ＊＊ ) and Predefined adjustment settings for the incubation environment parameters and the microscope parameters (T ｃｈ ＊ , R.H. ＊ , v ＊ ) and transmitting the selected adjustment settings for the incubation environment parameters to the incubation control unit (212); and further configured to: The control system of claim 11.

13. The control system (140) adjusts the selected adjustment setting (T ｃｈ ＊ , R.H. ＊ a microscope control unit (214) configured to operate the microscope (100) based on A target setpoint (T) of the at least one inspection parameter is input from the user interface (142). Ｓ ＊＊ ) and Predefined adjustment settings for the incubation environment parameters and the microscope parameters (T ｃｈ ＊ , R.H. ＊ , v ＊ ) and The selected adjustment setpoints (T ｃｈ ＊ , R.H. ＊ ) to at least one incubation control unit (212); [0023] The method according to claim 1, further comprising: The at least one incubation control unit (212) is configured to supply the incubation atmosphere based on the selected adjustment setting value (T ｃｈ ＊ , RH ＊ ) for the incubation environment parameters. The control system (140) of claim 1.

14. An inspection system (130) configured for microscopic inspection of a sample (120), said inspection system (130) comprising a microscope (100), an incubation environmental conditioning unit (110) connected to said microscope (100), and a user interface; The microscope (100) comprises illumination optics (118), a microscope stage (116), imaging optics (124), a sample chamber (106) configured to receive the sample, a microscope interface (108) configured to connect the incubation environmental conditioning unit (110) to the sample chamber (106), and an imaging optics chamber (122) separated from the sample chamber (106) and surrounding the imaging optics (124); the testing system (130) provides an incubation mode in which the sample chamber (106) is incubated by supplying an incubation atmosphere generated by the incubation environmental conditioning unit (110); The inspection system (130) further comprises a control system (140) according to claim 1. An inspection system (130).

15. the user interface (142) comprising at least one of a display and an input device; The inspection system (130) of claim 14.

16. The inspection system (130) is configured to input, via the user interface (142), the at least one inspection parameter (T Ｓ ) and displaying to a user a current value of at least one of the group of the at least one incubation environment parameter (RH), The inspection system (130) of claim 14.

17. The inspection system (130) adjusts the at least one incubation environment parameter (T ｃｈ , RH), The inspection system (130) of claim 14.

18. The atmospheric control module (216) controls the at least one incubation environment parameter (T ｃｈ , RH), The inspection system (130) of claim 17.

19. The microscope (100) further comprises a microscope housing (102) enclosing the illumination optics (118), the microscope stage (116) and the imaging optics (124), and an integral sample chamber (106) located within the microscope housing (102) and formed by a separate housing section (104) within the microscope housing (102); the imaging optics chamber (122) is located within the microscope housing (102) and is separated from the sample chamber (106); the separated housing section (104) comprises the microscope interface (108) configured to connect the incubation environmental conditioning unit (110) to at least one of the integrated sample chamber (106) and a stage-top sample chamber (206) disposed within the integrated sample chamber (106); The inspection system (130) provides a first incubation mode and a second incubation mode, in which the integrated sample chamber (106) is incubated by the provision of a first incubation atmosphere by the incubation environmental conditioning unit (110) in the first incubation mode, and in which the stage-top sample chamber (206) is incubated by the provision of a second incubation atmosphere by the incubation environmental conditioning unit (110) in the second incubation mode; the control system (140) is configured to operate the incubation environmental conditioning unit (110) and the microscope (100) based on the selected adjustment setting value for the selected one of the first incubation mode and the second incubation mode. The inspection system (130) of claim 14.

20. A method for microscopic inspection of a specimen (120) with an inspection system (130) as recited in claim 14, the method comprising: Providing a sample (120) in the sample chamber (106); Upon user input via the user interface (142), a target set point (T Ｓ ＊＊ ) providing - inspecting the sample (120) by the microscope (100) after reaching a defined threshold (RH') of the predefined adjustment settings for the at least one incubation environment parameter and the at least one microscope parameter of the incubation mode; The method includes:

21. The adjustment settings (T ｃｈ ＊ , R.H. ＊ , v ＊ ) is selected from one or more data sets (300), each data set including adjustment set points for one or more incubation environment parameters and / or microscope parameters that correlate to a target set point for the at least one inspection parameter; 21. The method of claim 20.

22. A method of operating an inspection system (130) configured for microscopic inspection of a sample (120), the inspection system (130) comprising a microscope (100), an incubation environmental conditioning unit (110) connected to the microscope (100), and a user interface (142), The microscope (100) comprises illumination optics (118), a microscope stage (116), imaging optics (124), a sample chamber (106) configured to receive the sample (120), a microscope interface (108) configured to connect the incubation environmental conditioning unit (110) to the sample chamber (106), and an imaging optics chamber (122) separated from the sample chamber (106) and surrounding the imaging optics (124); the testing system (130) provides an incubation mode in which the sample chamber (106) is incubated by supplying an incubation atmosphere generated by the incubation environmental conditioning unit (110); The method comprises: Upon user input via the user interface (142), preferably at least a target temperature (T Ｓ ＊＊ ) at least one target set point (T Ｓ ＊＊ , CO ２ ＊＊ ) (S1); Based on the received target setpoints of the at least one inspection parameter, a predefined adjustment setpoint (T ｃｈ ＊ , R.H. ＊ , v ＊ ) (S2); operating (S3) the incubation environment conditioning unit (110) and the microscope (100) based on the selected adjustment setting value; The method includes:

23. Operating the inspection system (130) of claim 14, 23. The method of claim 22.

24. A computer program having a program code for performing the method according to claim 22 when the computer program is executed on a processor or a control system (140) according to claim 1. Computer program.

Images