This application claims benefit to European Patent Application No. EP 22156635.9, filed on Feb. 14, 2022, which is hereby incorporated by reference herein.
The present invention relates to a microscope parameter controller for controlling microscope parameters, and to a microscope arrangement including such a microscope parameter controller, and to a method for controlling microscope parameters. The present invention also relates to controlling microscope parameters for handling, maintaining and/or imaging a sample before and/or during microscopic examination.
Especially in the field of microscopic examination of living samples like cells, it is of great interest to keep the sample as long as possible under favourable and stress-free environmental conditions. To this end, incubators can be used for generating an incubation atmosphere or microclimate adapted to the sample to be examined. Microscopic examination of a sample, particularly a living sample, typically involves handling the sample, maintaining/preserving the sample during and before examination and/or imaging the sample.
Incubators can be distinguished in stage top incubators, on the one hand, and cage incubators, on the other hand. Cage incubators are, typically, mounted to a standard microscope and comprise a large climatic chamber covering the main parts of the microscope, such as the objective revolver, the microscope stage including the sample carrier and an illumination condenser, such that a large volume needs to be incubated. On the other hand, a stage top incubator provides a small volume to be incubated as the stage top incubator only encloses the sample itself and is placed onto the microscope stage. While a cage incubator entails relatively high energy and gas consumption to maintain the required incubation atmosphere, a stage top incubator provides a small closed incubated space including connected supply conduits for supplying the desired incubation atmosphere.
When examining a sample, particularly using such a microscope and incubator, various microscope parameters have to be set automatically and/or by a user in order to be able to properly handle and maintain a sample before and during examination and to choose a suited imaging mode for imaging the sample. To this end, the user needs to have a good understanding of the sample properties, on the one hand, and of the technical parameters of the microscope including the incubator.
In an embodiment, the present disclosure provides a microscope parameter controller for controlling microscope parameters for handling, maintaining and/or imaging a sample, the microscope parameter controller being configured to determine at least one predefined setting of microscope parameters from one or more user-defined user settings of microscope parameters.
Subject matter of the present disclosure will be described in even greater detail below based on the exemplary figures. All features described and/or illustrated herein can be used alone or combined in different combinations. The features and advantages of various embodiments will become apparent by reading the following detailed description with reference to the attached drawings, which illustrate the following:
In view of the situation described above, there is a need for an improved control of microscope parameters for handling, maintaining and/or imaging a sample before and during examination by a microscope. According to embodiments of the invention, a microscope parameter controller, a microscope arrangement including such a microscope controller, a method for controlling microscope parameters, and a computer program for performing such a method are provided.
Some embodiments of the invention relate to a microscope parameter controller for controlling microscope parameters for handling, maintaining and/or imaging a sample, said microscope parameter controller being configured to determine at least one predefined setting of microscope parameters from one or more of user-defined user settings of microscope parameters.
“Handling” a sample comprises e.g. placing a sample onto a microscope stage of a microscope, removing the sample from the stage, and/or manipulating the sample during or before examination. “Maintaining” a sample comprises maintaining or preserving a sample before and/or during examination, particularly during imaging of the sample by means of the microscope and its accessories like a sample atmosphere incubator. “Imaging” a sample comprises illuminating the sample and imaging the sample by means of imaging optics of the microscope. Possible imaging methods comprise e.g. widefield, lightsheet and confocal microscopy including fluorescence microscopy.
“Microscope parameters for handling, maintaining and/or imaging a sample” comprise, especially in case of an incubated sample, sample incubation atmosphere parameters and microscope imaging parameters. Such parameters are, for instance, the temperature at the sample and/or of the incubation atmosphere, the relative humidity and a CO2 and/or N2 content of the incubation atmosphere, the incubation mode, like cage or stage top incubation or integrated sample chamber incubation as explained below, the kind of sample carrier, like Petri dish, multiwell plate, etc. Further, the imaging mode, like widefield, lightsheet or confocal microscopy, and in case of fluorescence microscopy, excitation wavelengths and emission or observation wavelengths. Further microscope parameters may be associated with illumination intensity, magnification of microscope objective and any other parameters influencing imaging, maintaining or manipulation of a sample.
“Determining at least one predefined setting of microscope parameters from one or more of user-defined user settings of microscope parameters” may generally comprise registering/remembering all or at least a part of user-defined user settings of microscope parameters, which user-defined user settings may be microscope parameter settings previously input by a user and/or otherwise used by a user. A microscope parameter setting input and/or otherwise used by a user comprises microscope parameters, which are input by a user and/or selected and/or accepted from a number of predefined microscope parameters and/or accepted microscope parameters from factory defaults (recommendations) such as e.g. certain temperature settings for certain specific samples types. Such a registering may be performed by storing the microscope parameter settings as input or otherwise used by a user in a memory/storage e.g. together with a time indication of the time of input/use of the respective user setting, and, optionally, together with a user identification (ID). The time indication may comprise a clock time and/or a sequence indication like “previous”, “penultimate” etc. or “first”, “second”, “third” etc. usage of input/used user setting. It is noted that it is not necessary to store each and every user-defined user setting input or used by a user. In an embodiment, the microscope parameter controller is a learning system, which adapts to a user, either user-specific or in relation to a plurality of users, such that e.g. the most frequently used user setting or e.g. the two most frequently used user settings are stored while other rarely or only once used user settings are discarded. Thus, alternatively or additionally to a time indication, a probability indication may be used for designating a user setting as the most, second most etc. frequently used user setting. In a simple embodiment, only the most frequently used user setting is stored. The microscope parameter controller is further configured to process said one or more user-defined user settings as will be explained in further detail below, to determine at least one predefined setting of microscope parameters, i.e. at least one microscope parameter setting defined by the microscope parameter controller, which microscope parameter setting thus constitutes, from a user perspective, a predefined microscope parameter setting. This one or more predefined microscope parameter setting may be suggested to a user at a next time of using the microscope and/or may be used to immediately start a microscope operation at a next time of using the microscope, as will be explained below.
In an embodiment, the microscope parameter controller is further configured to select one of the at least one predefined setting of microscope parameters for starting a microscope operation applying the selected predefined setting of microscope parameters. In other words, the microscope parameter controller automatically starts operation of the microscope with a selected predefined microscope parameter setting (e.g. fulfilling minimal requirements of microscope operation or adapting the microscope and its accessories to the needs of a specific sample type or organism) in order to more quickly achieve the operating status for examining and/or for maintaining a sample. Still, while the system already starts operation in order to reach the selected predefined setting of microscope parameters, a user may be allowed to change the selected predefined setting.
In an embodiment, the microscope parameter controller is further configured to receive a user selection of one of the at least one predefined setting of microscope parameters for a microscope operation applying the user-selected predefined setting of microscope parameters. As explained above, such a user-selected predefined setting of microscope parameters can also be regarded a user-defined user setting of microscope parameters and registered accordingly, e.g. regarding a frequency of use.
In an embodiment, the microscope parameter controller is further configured to determine at least one predefined setting of microscopic parameters user-specifically for one or more users of a microscope. This increase safety of operation and enables user-specific traceability of use.
In an embodiment, the at least one predefined setting of microscope parameters is determined in dependence of the current user of the microscope. In other words, the one or more predefined settings of microscope parameters are user-specifically proposed to a user.
In an embodiment, the at least one predefined setting of microscope parameters is determined as at least one of: one or more of the previous user settings; the most frequently used user setting; the second, third or nth, n>3, most frequently used user setting; and a setting comprising one or more mean values of one or more respective microscope parameters of previous user settings. This saves considerable time in defining a microscope parameter setting, especially in case of recurrent identical or similar settings.
In an embodiment, the microscope parameter controller is configured to control sample incubation atmosphere parameters of a sample incubation atmosphere provided for handling, maintaining and/or imaging of an incubated sample. In this embodiment, the microscope parameter controller can be regarded a “sample incubation atmosphere parameter controller”. This and the following embodiments and their advantages will be described in further detail below.
In an embodiment, the sample incubation atmosphere parameters comprise at least one of a temperature, a carbon dioxide concentration, a humidity content of the sample incubation atmosphere, and a kind of sample carrier used for carrying the sample.
In an embodiment, the microscope parameter controller is configured to render a graphical user interface providing at least one symbol configured to display the at least one predefined setting of microscope parameters and/or providing at least one widget configured to receive a user input for setting at least one microscope parameter.
The term “widget” shall, in the understanding used herein, refer to any element of interaction rendered as a part of a graphical user interface including, but not limited to, elements configured for selection and for the display of elements or collections such as buttons (including radio buttons, check boxes, toggle switches, toggle buttons, split buttons, cycle buttons), sliders, list boxes, spinners, drop-down lists, menus (including context menus and pie menus), menu bars, tool bars (including ribbons), combo boxes, icons, tree views, grid views, elements configured for navigation such as links, tabs and scrollbars, elements for textual input such as text and combo boxes, elements for output of information such as labels, tool tips, help balloons, status bars, progress bars and information bars, and containers such as (modal) windows, dialog boxes, palettes, frames and canvas elements.
In an embodiment, the present invention also relates to a microscope arrangement comprising a microscope and the microscope parameter controller according to embodiments of the present invention for controlling microscope parameters of the microscope.
In an embodiment, the microscope comprises a sample incubation system for providing a sample incubation atmosphere for handling, maintaining and/or imaging of an incubated sample, wherein the microscope parameter controller is configured to control sample incubation atmosphere parameters of a sample incubation atmosphere, and wherein the microscope parameter controller is preferably further configured for controlling other microscope parameters e.g. for a microscope imaging operation.
In an embodiment, the present invention also relates to a method for controlling microscope parameters for handling, maintaining and/or imaging a sample by means of a microscope, said method comprising the step of determining at least one predefined setting of microscope parameters from one or more user-defined user settings of microscope parameters.
In an embodiment, said method comprises the further step of selecting one of the at least one predefined setting of microscope parameters for starting a microscope operation applying the selected predefined setting of microscope parameters (e.g. based on type of organism analysed).
In another embodiment, the method comprises the further step of offering a user of the microscope to choose one of the at least one predefined setting of microscope parameters for a microscope operation applying the user-selected predefined setting of microscope parameters. Such a user-selected predefined setting of microscope parameters can also be regarded a user-defined user setting of microscope parameters.
In an embodiment, the microscope parameters are or comprise sample incubation atmosphere parameters, as already discussed above, of a sample incubation atmosphere provided for handling, maintaining and/or imaging of an incubated sample.
In an embodiment, the invention also relates to a computer program with a program code for performing the method according to embodiments of the invention as described above, when the computer program is run on a processor, particularly on a microscope parameter controller according to embodiments of the present invention as described above.
In the following, the figures will be described comprehensively, same reference signs relating to same or at least functionally same elements. The figures and their description are to be understood as illustrating, without loss of generality, examples of a microscope parameter controller, a microscope, and a method for controlling microscope parameters according to embodiments of the present invention.
An embodiment of a microscope parameter controller is shown in
“Microscope parameters for handling, maintaining and/or imaging a sample” thus particularly comprise, in case of an incubated sample, sample incubation atmosphere parameters and microscope imaging parameters. Such parameters are, for instance, the temperature at the sample and/or of the incubation atmosphere, the relative humidity and a CO2 and/or N2 content of the incubation atmosphere, the incubation mode, like cage or stage top incubation or integrated sample chamber incubation as explained below, the kind of sample carrier, like Petri dish, multiwell plate, etc. Further, the imaging mode, like widefield, lightsheet or confocal microscopy, and in case of fluorescence microscopy, excitation wavelengths and emission or observation wavelengths. Further microscope parameters may be associated with illumination intensity, magnification of microscope objective and any other parameters influencing imaging of a sample.
Through its user interface 148, the microscope parameter controller 140 is configured to receive user input setting microscope parameters for handling, maintaining and/or imaging the sample 120. “Determining at least one predefined setting of microscope parameters from one or more of user-defined user settings of microscope parameters” may generally comprise registering/remembering all or at least a part of user-defined user settings of microscope parameters, which user-defined user settings may be microscope parameter settings previously input by a user and/or otherwise used by a user, e.g. by selecting a predefined microscope parameter setting as suggested by the system. Such a registering may be performed by storing the microscope parameter settings as input or otherwise used by a user in a cache, buffer or other memory/storage e.g. together with a time indication of the time of input/use of the respective user setting, and, optionally, together with a user identification (ID). The time indication may comprise a clock time and/or a sequence indication like “previous”, “penultimate” etc. or “first”, “second”, “third” etc. input/used user setting. It is noted that it is not necessary to store each and every user setting input or used by a user. In an embodiment, the microscope parameter controller is a learning system, which adapts to a user (or to the users) such that e.g. the most frequently used user setting or e.g. the two most frequently used user settings are stored while other rarely or only once used user settings are discarded. Thus, alternatively or additionally to a time indication, a probability indication may be used for designating a user setting as the most, second most etc. frequently used user setting. In a simple embodiment, only the most frequently used user setting is stored. The microscope parameter controller 140 is further configured to determine at least one predefined setting of microscope parameters from one or more of the tracked user-defined user settings as will be explained further below.
The controller 140 may include one or more processors. The processor(s) can be of any type and can be provided in any number and at any position and in any component of the microscope 100. As used herein, the term processor(s) may refer to any type of computational circuit, such as, but not limited to, a microprocessor, a microcontroller, a complex 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 multiple core processor, a field programmable gate array unit (FPGA). Other types of processing circuits that may be included in the controller 140 may be a custom circuit, an application-specific integrated circuit (ASIC), or the like, such as, for example, one or more circuits (such as a communication circuit) for use in wireless devices like mobile telephones, tablet computers, laptop computers, two-way radios, and similar electronic systems.
The memory/storage of the controller 140 may comprise one or more memory elements suitable to the particular application, such as a 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 disks (CD), flash memory cards, digital video disk (DVD), and the like.
Before discussing the way of determining at least one predefined setting of microscope parameters by the microscope parameter controller 140 in more detail, the embodiment of microscope 100 shown in
Sample 120 can be placed onto microscope stage 116. Microscope housing 102 encloses an illumination optics 118, the microscope stage 116 and an imaging optics 124. An integrated sample chamber 106 is located within the microscope housing 102 and formed by a separated housing section 104 within said microscope housing 102. The housing 102 comprises a hinged lid 109, which provides, in its opened state, direct access to the microscope stage 116 for placing, removing and/or manipulating the sample 120 in the sample chamber 106.
The embodiment shown in
The construction of the microscope housing section 104 allows—after closing the lid 109—to form a dedicated sample chamber 106, which constitutes a closed space, which can be incubated such that sample 120, like living cells, can be kept under favourable and stress-free environmental conditions. To this end, microscope 100 further comprises a sample incubation system 110. In the embodiment shown in
Suitable incubation atmospheres comprise, e.g., air with a predefined content of H2O (water or water vapour, relative humidity) and a predefined content of CO2 (carbon dioxide). It may also be desirable to conduct hypoxia experiments with a deficiency of oxygen in the atmosphere. For further details about specific parameters and suitable or preferred ranges of sample incubation atmosphere parameters, please refer to the description of the following figures.
Note that controlling the relevant parameters (incubation atmosphere parameters like temperature, humidity, carbon dioxide concentration, oxygen concentration, and other parameters like fan speed, and possibly further microscope parameters relating to imaging of a sample as explained above), in this embodiment, will be performed in an automated manner by means of the microscope parameter controller 140. To this end, target setpoints for at least a part of said parameters can be set by a user of the microscope 100, other parameters may be predefined or even fixedly predetermined. In order to control said incubation atmosphere parameters, it is preferred to arrange sensors in or at least one of the conduits 108, the sample chamber 106 and/or the microscope stage 116 close to the sample 120.
For increasing the lifespan of the imaging optics 124, and, particularly, in case of using immersion objectives, an atmosphere control for the imaging optics chamber 122 may be provided. Such an atmosphere control may also be operated by the microscope parameter controller 140.
As already explained above, microscope parameter controller 140 is configured to control the operation of the sample incubation system 110. To this end, in this embodiment, the microscope parameter controller is connected to a sample incubation controller 112, which is controlled by microscope parameter controller 140 and provided for implementing and monitoring/checking the sample incubation atmosphere parameters as set by the microscope parameter controller 140. At the backside of the housing section 104, there is an atmosphere regulation module 113, which includes the above-mentioned sensors for detecting actual values of incubation atmosphere parameters and/or for receiving such sensor signals. Atmosphere regulation module 113 is connected to the sample incubation controller 112 of the sample incubation system 110. In that way, a feedback control can be implemented to set a group of sample incubation atmosphere parameters to the desired setpoints. It is noted that, in other embodiments, the sample incubation controller 112 can be part of or integrated into microscope parameter controller 140.
Apart from the above-described sample chamber incubation, another incubation mode, namely a stage top incubation may be realised by a stage top sample chamber 156 as indicated by dashed lines. A connection to an opening 114 and/or a conduit 108 can also be established in order to provide the respective incubation atmosphere into the smaller stage top sample chamber 156. As explained further below, the user can select which incubation mode to use, in this embodiment, either sample chamber incubation or stage top incubation.
Graphical user interface 142 of the microscope parameter controller 140 displays various symbols 244a, 244b, and 244c for parameters, which are, at least in part, adjustable by corresponding widgets 246a, 246b, and 246c. In the embodiment shown, 244a is a symbol for the temperature of the sample or of the sample incubation atmosphere, 244b is a symbol for the relative humidity of the incubation atmosphere, and 244c is a symbol for the carbon dioxide (CO2) concentration in the sample chamber 106. Said parameters may be set either by a user or may be predefined by the microscope parameter controller 140, optionally including the option of a user altering a predefined parameter. In the embodiment shown in
The right side of
By user input via widgets 246a, 246c and optionally 246b, target setpoints of sample incubation atmosphere parameters, namely temperature, CO2 concentration and optionally relative humidity can be input by a user. The microscope parameter controller 140 with the support of the sample incubation controller 112 controls the sample incubation system 110 to generate and maintain the desired incubation atmosphere inside the sample chamber 106 as explained above in connection with
Other widgets may be provided in graphical user interface 142 configured to receive user settings of other microscope parameters. For example, a user may select the kind of sample carrier by widget 346g, the kind of microscopic imaging mode by widget 346h, the fluorescence channel for observing a sample image by widget 346i, etc.
The microscope parameter controller 140 of this embodiment is configured to register a user setting of microscope parameters represented by widgets 246a to 246c, and 346d to 346i. Such a registering may comprise storing the user setting of microscope parameters in a memory designated to this purpose of the microscope parameter controller 140, and keeping it e.g. together with a suitable time and/or probability indication, as explained above, even if the respective user has completed sample examination and, possibly, turned off the microscope parameter controller 140. The microscope parameter controller is further configured to determine at least one predefined setting of microscope parameters from the user-defined user setting(s) such that the graphical user interface 142 of the microscope parameter controller 140 may display such a predefined setting according to
As shown in
In an embodiment, the microscope parameter controller 140 is further configured to select the predefined setting of microscope parameters as represented by widget 348 for starting a microscope operation applying the selected predefined setting of microscope parameters. In other words, the microscope parameter controller 140 automatically starts microscope 100 with microscope parameters as defined in
The inventors found that a specific user, and sometimes even a plurality of users using the same microscope 100, typically chooses the same or at least essentially the same microscope parameters, at least when examining the same kind of sample. Thus, displaying the predefined setting of microscope parameters in the form of symbol 348 to a user saves the user from again defining setpoints of microscope parameters as illustrated in
Embodiments of the present invention thus, in a particular example, allow a user to examine zebrafish in Petri dishes at 28° C. and a predetermined humidity and CO2 concentration initially in transmitted light (corresponding to a first predefined microscope parameter setting), and subsequently in confocal fluorescence microscope imaging (corresponding to a second predefined microscope parameter setting) using a microscope being able to provide the corresponding imaging modes, since the microscope parameter controller 140 is able of self-learning these two predominantly used microscope parameter settings.
This situation is illustrated by
It is noted that a user identity may not be required for the embodiment according to
In an embodiment, it is, however, possible to register user-defined user settings of microscopic parameters user-specifically for one or more users of the microscope 100. The user-specific tracking may be performed by the microscope parameter controller 140 by using, for instance, a user ID, which the user uses when logging on to the computer/PC 146 as shown in
In the embodiments of
As used herein the term “and/or” includes any and all combinations of one or more of the associated listed items and may be abbreviated as “/”.
Although some aspects have been described in the context of an apparatus, it is clear that these aspects also represent a description of the corresponding method. Analogously, aspects described in the context of a method step also represent a description of a corresponding feature of a corresponding apparatus.
Some or all of the method steps may be executed by (or using) a hardware apparatus, like for example, a processor, a microprocessor, a programmable computer or an electronic circuit. In some embodiments, some one or more of the most important method steps may be executed by such an apparatus.
Depending on certain implementation requirements, embodiments of the invention can be implemented in hardware or in software. The implementation can be performed using a non-transitory storage medium such as a digital storage medium, for example a floppy disc, a DVD, a Blu-Ray, a CD, a ROM, a PROM, and EPROM, an EEPROM or a FLASH memory, having electronically readable control signals stored thereon, which cooperate (or are capable of cooperating) with a programmable computer system such that the respective method is performed. Therefore, the digital storage medium may be computer readable.
Some embodiments according to the invention comprise a data carrier having electronically readable control signals, which are capable of cooperating with a programmable computer system, such that one of the methods described herein is performed.
Generally, embodiments of the present invention can be implemented as a computer program product with a program code, the program code being operative for performing one of the methods when the computer program product runs on a computer. The program code may, for example, be stored on a machine readable carrier.
Other embodiments comprise the computer program for performing one of the methods described herein, stored on a machine readable carrier.
In other words, an embodiment of the present invention is, therefore, a computer program having a program code for performing one of the methods described herein, when the computer program runs on a computer.
A further embodiment of the present invention is, therefore, a storage medium (or a data carrier, or a computer-readable medium) comprising, stored thereon, the computer program for performing one of the methods described herein when it is performed by a processor. The data carrier, the digital storage medium or the recorded medium are typically tangible and/or non-transitionary. A further embodiment of the present invention is an apparatus as described herein comprising a processor and the storage medium.
A further embodiment of the invention is, therefore, a data stream or a sequence of signals representing the computer program for performing one of the methods described herein. The data stream or the sequence of signals may, for example, be configured to be transferred via a data communication connection, for example, via the internet.
A further embodiment comprises a processing means, for example, a computer or a programmable logic device, configured to, or adapted to, perform one of the methods described herein.
A further embodiment comprises a computer having installed thereon the computer program for performing one of the methods described herein.
A further embodiment according to the invention comprises an apparatus or a system configured to transfer (for example, electronically or optically) a computer program for performing one of the methods described herein to a receiver. The receiver may, for example, be a computer, a mobile device, a memory device or the like. The apparatus or system may e.g. comprise a file server for transferring the computer program to the receiver.
In some embodiments, a programmable logic device (for example, a field programmable gate array) may be used to perform some or all of the functionalities of the methods described herein. In some embodiments, a field programmable gate array may cooperate with a microprocessor in order to perform one of the methods described herein. Generally, the methods are preferably performed by any hardware apparatus.
While subject matter of the present disclosure has been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered illustrative or exemplary and not restrictive. Any statement made herein characterizing the invention is also to be considered illustrative or exemplary and not restrictive as the invention is defined by the claims. It will be understood that changes and modifications may be made, by those of ordinary skill in the art, within the scope of the following claims, which may include any combination of features from different embodiments described above.
The terms used in the claims should be construed to have the broadest reasonable interpretation consistent with the foregoing description. For example, the use of the article “a” or “the” in introducing an element should not be interpreted as being exclusive of a plurality of elements. Likewise, the recitation of “or” should be interpreted as being inclusive, such that the recitation of “A or B” is not exclusive of “A and B,” unless it is clear from the context or the foregoing description that only one of A and B is intended. Further, the recitation of “at least one of A, B and C” should be interpreted as one or more of a group of elements consisting of A, B and C, and should not be interpreted as requiring at least one of each of the listed elements A, B and C, regardless of whether A, B and C are related as categories or otherwise. Moreover, the recitation of “A, B and/or C” or “at least one of A, B or C” should be interpreted as including any singular entity from the listed elements, e.g., A, any subset from the listed elements, e.g., A and B, or the entire list of elements A, B and C.
Number | Date | Country | Kind |
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22156635.9 | Feb 2022 | EP | regional |