DE102012101086A1 - Device for detecting image of sample or for detecting variable of sample, comprises container for sample, and sensor in container, where sensor indicates optical behavior corresponding to variable - Google Patents

Abstract

The device (1) comprises a container (40) for a sample, and a sensor (30) in the container. The sensor indicates the optical behavior corresponding to the variable. A module (2) is provided, which is assigned in the container. An image detector (4) is provided for capturing an image of the sample. An optical system (5) is provided for detecting the optical behavior of each sensor. An independent claim is also included for a method for detecting an image of a sample or for detecting a variable of a sample.

Description

The invention relates to a device with which both at least one image of a sample can be detected and at least one variable of the sample can be detected. Likewise, the invention relates to a method for this purpose.

When examining samples, it is often of interest to record different types of data in parallel in order to better understand processes in the sample. An example of this, to which the invention is expressly not limited, is the monitoring of cell cultures. On the one hand, it is of interest to observe the cells of the culture in order to obtain morphological information about the cells, on the other hand, at the same time recorded information about the environmental conditions of the cells, that is variable of the sample, allows an improved understanding of the processes in the cell culture.

This is how the article describes "Automated Multiparametric Platform for High-Content and High-Throughput Analytical Screening on Living Cells" by Thomas Geisler, Johann Ressler, Hartmann Harz, Bernhard Wolf and Rainer Uhl the study of cell cultures, which are located in a large number of cavities in a plate. In the cavities optical sensors are provided which indicate the pH value in the cell culture and the oxygen partial pressure prevailing there by changing their luminescence behavior. A specially designed microscope can be moved from cavity to cavity to capture images of cell cultures.

The German patent DE 199 49 029 C2 deals with the characterization of a culture fluid, for example in a bioreactor. The cells are microscopically imaged in the culture fluid using a dark field illumination. Alternatively, a bright field illumination is possible. The image analysis involves a comparison of the intensities of the scattered light from the cell interior and the scattered light from the cell edge to determine the vitality of the culture fluid.

The European patent application EP 1 811 017 A1 discusses a device for imaging cells in an incubator. For image capture incubator and camera are moved relative to each other.

In prior art devices, e.g. In the above-referenced article, image capture devices, such as a microscope, are moved over an array of a plurality of samples. Particularly in systems which have to cope with a high throughput, this means correspondingly fast movements of the image capture device. This promotes high wear. Even monitoring just one sample requires the entire microscope setup, which is problematic when used in systems with limited space requirements.

It is therefore an object of the invention to provide a device for detecting at least one image of at least one sample and / or for detecting at least one variable of the at least one sample, which is designed to be compact and space-saving, which makes it possible to monitor a plurality of samples, and which, moreover, is designed to significantly reduce wear and tear on the prior art.

This object is achieved by a device according to claim 1.

It is a further object of the invention to provide a method for detecting at least one image of at least one sample and / or for detecting at least one variable of the at least one sample, with which one or more samples can be monitored in a space-saving and low-wear manner.

This object is achieved by a method according to claim 19.

The device according to the invention has at least one container for each sample. By container is meant any feature of the device which is designed to receive a sample. In each container at least one sensor is provided, which shows a dependent on at least one variable of the sample optical behavior. The sensors of the device are thus selected in accordance with the variable to be determined during a measurement process of the respective sample to be examined. The variable may be, for example, a temperature, a pressure, a substance concentration, an ion concentration, a pH, or a partial pressure of a gas. It will be understood by those skilled in the art that any variance may be determined by the device for which suitable sensors are available. The optical behavior may be, for example, a color change of the at least one sensor, a change in the reflectivity of the at least one sensor, or a luminescence phenomenon. Luminescence encompasses at least phosphorescence and fluorescence.

According to the invention, at least one module is provided in the device, wherein the at least one module is associated with at least one container. For every container that has a particular Module is associated with the module can be detected at least one image of the sample in the respective container and the optical behavior of each located in each container sensor. If several containers are assigned to a module, then the at least one image of each sample can be detected as at least one common image of the samples in the containers. In principle, it is also possible to use only one of the possibilities of image recording or detection of the optical behavior of at least one sensor in a particular examination, but the module is designed to perform both. During an investigation, the association between a module and the at least one container is fixed, so the module is not moved from sample to sample or from container to container. Thus, an important cause of wear is eliminated. Since facilities for the movement of the image capture device from sample to sample eliminated, the device can make space-saving than the prior art.

In preferred embodiments, the module includes an image detector for capturing at least one image of at least one sample, imaging optics associated with the image detector, and an optical system for detecting the optical behavior of each sensor.

In embodiments of the invention, the at least one sensor is designed as a sensor spot. Moreover, the at least one sensor is fixed at a position within the container. The sensor spot may, for example, comprise a matrix, such as a polymer matrix, in which a substance is embedded which exhibits an optical behavior dependent on at least one variable to be determined. It must be ensured that the sensor, and in the special embodiment, the substance, in the examination of a sample in such contact with the material of the sample passes that the sensor function can be met. If the variable is a substance concentration, an ion concentration, a pH value or a partial pressure of a gas, then the sensor or the substance must come into material contact with the material of the sample. If the variable is a temperature, then heat transfer between the sample and the sensor must be possible. For detecting the optical behavior, the sensor spot is advantageously fixed to a container wall. The use of a sensor spot in place of e.g. added substance as a solution has the advantage that the sample itself is affected to a much lesser extent by not at all by the sensor. Especially in the monitoring of cell cultures, certain substances used in sensors to fulfill their sensor function can affect the cells, so that the results of such an investigation are falsified. However, if the substance is located in a sensor spot, contact of the substance with the cells is largely excluded, whereas contact with the solution in which the cells are located is possible. In this way, the sensor spot can be used to analyze about the chemical composition of this solution without affecting the cells.

In embodiments, at least one illumination light source may be provided in the module, which serves to illuminate the sample during image acquisition. It is also possible that this illumination light source is adjustable, wherein the control can be done depending on the embodiment by interaction of the module with an external control system or by a control device in the module.

In embodiments of the device according to the invention, in which the optical behavior of the at least one sensor is a luminescence phenomenon, the optical system for detecting the optical behavior of the at least one sensor comprises at least one excitation light source for exciting the luminescence phenomenon and a detector for detecting the luminescence phenomenon. For excitation of the luminescence, the excitation light source can emit, for example, constant continuous light, individual light pulses, pulse trains, or intensity-modulated continuous light, depending on the measuring method. It is also possible to use more than one excitation light source, for example when different luminescence phenomena are to be excited and for this excitation light from different wavelength ranges is required.

The imaging optics may include a variable focal length lens. In particular, it may be a liquid lens. In this case, the focal length is changed by deformation. Such a deformation can be effected by mechanical action on the lens, for example via piezo elements or servomotors, but the deformation of the liquid lens by applying an electrical voltage is particularly advantageous. This is completely dispensed with movable mechanical elements, which in turn contributes to the reduction of wear.

A configuration of the imaging optics can be changed by a drive, for example, the relative position of optical elements of the imaging optics to each other can be changed. This change in the configuration can be done for example by servomotors or piezo elements. The change of the configuration serves to change the imaging properties of the imaging optics, such as the variation of a focal length, to focus the image of at least one sample on the image detector. Likewise, it is possible to change a distance between the imaging optics and a respective container by a drive; Here, too, the respective sample should be focused by the imaging optics.

In an advantageous development, the module for controlling the aforementioned drives and / or for controlling the variation of the focal length of the lens via an autofocus device. Alternatively, an autofocus function can be realized by interaction of the module with an external system.

In embodiments, at least one container is associated with a reflector on a side of the container opposite the module. This is particularly advantageous if the module has at least one illumination device for illuminating the sample during image acquisition. In this case, the light from the at least one illumination device is reflected back to the sample after passing through the sample through the reflector, so that the illumination of the sample is improved. Such a reflector may be assigned separately to a container. But it is also possible that a common cover for a plurality of containers is designed to be reflective.

Embodiments of the device may be designed so that the device can be used in an incubator without being impaired in its function. Especially with studies in the field of biology or medicine, for example in the study of cell cultures, this is an advantage.

In order to avoid that unwanted reflections, such as the light of lighting devices in the module or the light of excitation light sources in the optical system for detecting the optical behavior of at least one sensor, for example on a container wall, interfere with the investigation of the sample, in a beam path of the imaging optics and / or at least one polarizing element and at least one polarizing filter are provided in a beam path of the optical system.

Likewise, optical filters with a wavelength-dependent transmission behavior can be provided in a beam path of the imaging optics and / or in a beam path of the optical system. In particular, such optical filters may be provided between the illumination light source and the container and / or between the excitation light source and the container and / or between the image detector and the container and / or between a luminescence light detector and the container.

In embodiments, the optical system may include at least one optical fiber for detecting the optical behavior of at least one sensor. The optical waveguide can serve, for example, to guide excitation light from an excitation light source in the module to at least one sensor, and / or serve to guide luminescence light from at least one sensor to a photodetector in the module.

The module may be designed so that within the module a plurality of carriers are formed, which are arranged in the direction of the module to the at least one module associated with the container in succession. Functional units of the module can be distributed to these carriers, for example, the optical system for detecting the optical behavior can be arranged on a first carrier, the imaging optics can be provided with the image detector on a second carrier, and illuminating light sources can be arranged on a third carrier , It must of course be ensured that the beam paths of the imaging optics and the optical system are not interrupted by other elements of the module. In this case, it may be helpful to guide at least a section of a beam path in a light guide. By arranging the functional units of the module on a plurality of carriers, the lateral extent of the module, that is to say in directions perpendicular to the direction from the module to the at least one container associated with the module, can be reduced. This sometimes favors the installation of a module in a system, in particular several modules can thus be set closer together so that more samples can ultimately be examined on a given area than if modules with a larger lateral extent are used.

The device according to the invention can be used particularly advantageously for the examination of a multiplicity of samples. In certain embodiments, the containers with the samples are arranged regularly, for example in the manner of a matrix or a honeycomb. Since the assignment between modules and containers is fixed during the examination, no effort has to be made to position a movable image capture device accurately during the examination. The data acquired by the modules, that is to say for each module at least the at least one image of at least one sample and / or the optical behavior of at least one sensor, are provided in embodiments for an external system for further evaluation; This can be done advantageously by a single external interface of the device. Likewise, in other embodiments, an evaluation of the acquired data within the device is possible. The further evaluation may include steps determine from the detected optical behavior of the at least one sensor at least one variable of a respective sample. It is clear to the person skilled in the art that prior calibrations of the at least one sensor and / or the respective module may be required for this purpose. Likewise, it is clear to the person skilled in the art that such an evaluation of the data acquired by a module can, of course, also be carried out and, as a rule, must also be carried out if a large number of samples is not examined, but only a single sample.

With the device, a plurality of samples can be examined substantially simultaneously. At the same time, here it means that, in contrast to the prior art, it is not necessary to move an image capture device or a device for detecting the optical behavior of a sensor from sample to sample or from container to container. It would be conceivable, for example, to activate the image detectors of different modules sequentially in time, so that an image is acquired only in the activated state, and then to supply this image for further evaluation. The typical time scale for the temporal successive activation of the image detectors is determined by the switching times of today's electronics, and is orders of magnitude shorter than the time it takes to move an image capture device from one container to the next in the prior art. In this sense, the image capture takes place at the same time in a practical sense compared to the prior art.

Alternatively, it is also possible to assign internal memories in the module to the image detectors, so that these image detectors can perform the acquisition of an image independently of one another and, in particular, actually at the same time. The acquired image is then first stored in the internal memory, and after the image acquisition, the individual internal memory can be quite time sequentially read out.

Analogous embodiments also apply to detectors of the optical system for detecting the optical behavior of at least one sensor.

The method according to the invention for detecting at least one image of at least one sample and / or for detecting at least one variable of the at least one sample proceeds as follows:

Each sample is assigned at least one sensor which exhibits an optical behavior dependent on the at least one variable. At least one module is provided which has an image detector and an imaging optic associated therewith. Each module is assigned at least one sample for a study. The module is therefore not moved from sample to sample in the case of examining several samples. With each module, at least one image of the at least one sample assigned to the respective module is detected. Furthermore, the optical behavior of at least one sensor is detected with an optical system provided for this purpose in the module. It is expressly also possible to use only one of the two options in certain examinations, that is, to perform only the image acquisition or to detect only the optical behavior of the at least one sensor. Finally, the data obtained, that is to say the at least one image and / or the optical behavior of the at least one sensor, can be transmitted to an external processing device or to a processing device provided in the device for evaluation in a manner familiar to the person skilled in the art.

The steps of image acquisition and detection of the optical behavior of the at least one sensor may also be performed repeatedly to track the behavior of the at least one sample over time. This also includes the detection of film sequences of both the sample and the optical behavior of the at least one sensor. The data transmission to the processing device is adapted to the acquisition of the data in a manner familiar to the person skilled in the art.

In one embodiment of the method, the module has at least two illumination light sources for illuminating a respective sample. These illumination light sources are activated in temporal change, so that, depending on the respectively activated illumination light sources, different illumination situations, among others different shadows, result in the sample. At least one image of the sample is acquired for each illumination situation.

The detection of at least one image of the sample and the detection of the optical behavior of the at least one sensor can be carried out in one embodiment of the method for a plurality of samples.

Due to the fixed association between the module and at least one sample in the above sense, the method is particularly predestined to perform this simultaneously for the plurality of samples. At the same time, this is again to be understood in the sense already explained above. In the method, the imaging optics, the image detector, the optical system, illumination light sources or excitation light sources can be controlled by an external control system. Likewise it is possible a part of these or all these components by a on control system provided for each module.

The method can be used in particular for the investigation of a cell culture. In this case, by capturing the at least one image of the sample, in this case the cell culture, information about the cell morphology and / or cell vitality and / or cell growth can be obtained. By capturing the at least one variable, information about the environmental conditions of the cell culture and / or about the metabolism of the cell culture is obtained.

The inventive method can be carried out in particular with a device according to the invention.

Embodiments of the invention will be explained in more detail below with reference to attached drawings. Show it:

1 a schematic representation of an embodiment of the device according to the invention;

2 a perspective view of a specific embodiment of the device according to the invention;

3 a further schematic representation of an embodiment of the device according to the invention;

4 a further schematic representation of an embodiment of the device according to the invention;

5 a further schematic representation of an embodiment of the device according to the invention;

6 a perspective view of another specific embodiment of the device according to the invention;

7 a further schematic representation of an embodiment of the device according to the invention;

8th a further schematic representation of an embodiment of the device according to the invention with a plurality of containers; and

9 a further schematic representation of an embodiment of the device according to the invention, in which a module two containers are assigned.

In the drawings, identical reference numerals are used for the same or equivalent elements. Furthermore, in the drawings, for clarity, only those reference numerals are shown, which are required for the description of the respective drawing.

1 shows a schematic representation of the device according to the invention 1 , In a container 40 the device 1 is a sample 100 filled. It is indicated that in the case shown it is a liquid sample 100 is. An example of such a liquid sample 100 would be about a cell culture in aqueous solution. Solid or gaseous samples would also be conceivable in principle. In the case of gaseous samples, of course, the container must be designed gas-tight accordingly. In the container 40 there is at least one sensor 30 which is one of at least one variable of the sample 100 dependent optical behavior; in the case shown here are two sensor spots 30 shown, which are on a wall 41 of the container 40 are located. The container 40 is a module 2 associated with the at least one image of the sample 100 and the optical behavior of each sensor 30 are detectable. For this purpose, the module comprises an imaging optics 3 which the sample 100 or the container 40 on one in the module 2 located image detector 4 maps. The image detector 4 then draw at least one picture of the sample 100 or the container 40 on. Further, in the module 2 an optical system 5 for detecting the optical behavior of each sensor 30 intended. Only for the sake of completeness it should be mentioned that the container wall 41 for all in image acquisition and detection of the optical behavior of the at least one sensor 30 must be permeable to involved light wavelengths. It is further shown that individual components of the module 2 on a common carrier 21 can be located here, especially the image detector 4 and the optical system 5 , Preferably, the sensor spots 30 on the container wall 41 fixed.

Shown are also an optically polarizing element 13 and a polarizing filter 14 as in some embodiments of the device according to the invention 1 in a beam path 31 the imaging optics 3 can be provided. The optically polarizing element 13 and the polarizing filter 14 serve to reflect the illumination light, which in embodiments for illuminating the sample 100 is used, from the container wall 41 to suppress, and so the quality of image capture by the photodetector 4 to improve. In other embodiments, an optically polarizing element and a polarizing filter are in one beam path 32 of the optical system 5 provided, or both in the beam path 31 the imaging optics 3 and in the beam path 32 of the optical system 5 , This can also be a optically polarizing element or a polarizing filter act, the two beam paths 31 . 32 is common. Optically polarizing element and polarizing filter in the beam path 32 of the optical system 5 serve to disturbing reflections of the excitation light, which in some embodiments by an excitation light source in the optical system 5 can be emitted, on the container wall 41 to reduce.

2 is a perspective view of a specific embodiment of the device according to the invention 1 , In this case, there is only one sensor spot 30 in the container 40 intended. A sample is not shown here. In the module 2 are the imaging optics 3 , the image detector 4 , and the optical system 5 ,

In the embodiment shown, the optical behavior of the sensor 30 , which depends on at least one variable of a sample, a luminescence behavior. The optical system 5 accordingly comprises an excitation light source 7 for stimulating the luminescence and a photodetector 8th to get away from the sensor 30 to detect emitted luminescence. Further, in this embodiment, a reference light source 60 present when calibrating the optical system 5 is used.

In the module 2 Here are also two illumination light sources 6 shown, which are used to illuminate a sample in the detection of an image of the sample. In other embodiments, more than two illumination light sources may also be used 6 or only one illumination light source 6 be provided.

The imaging optics 3 comprises at least one lens in the illustrated embodiment 9 , In embodiments, this is a lens of variable focal length. This can be the focal length of the lens 9 by deformation of the lens 9 be changed. Such deformations are possible, for example, in a liquid lens. The deformations can be effected by mechanical elements such as actuators or piezo elements forcing forces on the lens 9 However, the deformations are particularly advantageous by applying an electrical voltage to the lens 9 causes; no moving elements are required, which significantly reduces wear. The change in the focal length of the lens 9 serves to focus a sample in the container 40 , for example, one directly to the container wall 41 adjacent area of the sample.

Also shown is an optical filter 15 between module 2 and containers 40 , The optical filter 15 has three filter sections here 15a . 15b and 15c , The filter sections 15a . 15b . 15c have a wavelength-dependent transmission behavior, wherein the filter sections 15a . 15b . 15c with regard to this transmission behavior can differ from each other.

A first filter section 15a is the imaging optics 3 and the illumination light sources 6 assigned, and serves to light from the illumination light sources 6 suitable to filter before hitting the sample. In embodiments, for example, wavelength ranges of the illumination light which could falsify the examination of a sample can be filtered out. Such a falsification could result, for example, from the fact that certain wavelength ranges of the illumination light in a sample to be examined during the investigation trigger unwanted chemical reactions or that certain wavelength ranges of the illumination light can kill the cells of a cell culture to be examined. In addition, the first filter section 15a also serve, excitation light from the excitation light source 7 , which is attached to the container wall 41 reflected or scattered back to the sample, and / or luminescence from the sensor 30 that has been scattered in the sample, from the imaging optics 3 keep away, and so improve the quality of a captured image.

A second filter section 15b is the excitation light source 7 assigned. The second filter section 15b may be required to remove light wavelength ranges from the excitation light that is the sensor 30 negatively affect or in the sensor 30 stimulate such luminescence phenomena, which are not desirable in a specific examination to be carried out, so that it is thus ensured that only the luminescence phenomena required for an examination are excited. A negative influence on the sensor 30 by certain wavelength ranges of the excitation light may consist in that through these wavelength ranges a substance in the sensor 30 which shows the luminescence is destroyed. Furthermore, the second filter section 15b be necessary to remove wavelength ranges from the excitation light, which could distort the study of a sample, as it already in connection with the first filter section 15a and wavelength regions of the illumination light has been discussed.

A third filter section 15c is the photodetector 8th assigned to the sensor 30 to emit emitted luminescent light, before this on the photodetector 8th meets. Through the filter section 15c can unwanted luminescent light, ie those of a specific Lumineszenzerscheinung, although by the excitation light in spite of Any filtering through the second filter section 15b was excited, but does not belong to the luminescence phenomena relevant for the respective investigation, from the photodetector 8th be kept away. In addition, through the filter 15c Light of the illumination light sources 6 and also the excitation light source 7 from the photodetector 8th be kept away, which on the container wall 41 has been reflected or which has been backscattered by a sample.

The optical filter 15 may further be used together with an optically polarizing element 13 and a polarizing filter 14 , what a 1 are shown used.

Because the optical filter 15 easier to change than the excitation light source 7 or the illumination light sources 6 , by using different optical filters, the device can 1 easily and quickly adapted to different measuring tasks.

The illustration also shows one in the module 2 provided control system 44 shown. The control system 44 is in this embodiment for controlling the imaging optics 3 , the image detector 4 , the lighting light sources 6 and the optical system 5 provided, thus thus in particular also for controlling the excitation light source 7 and the photodetector 8th , In other embodiments, the control system is 44 provided for controlling only a part of said components, while other components of the module 2 be controlled by an external control system.

In the embodiment shown, the module has 2 furthermore via a processing system 46 which is the one from the image detector 4 and the photodetector 8th collected data for further evaluation.

3 shows a further schematic representation of the device according to the invention 1 , Most of the illustrated elements have already been linked to the 1 discussed. In this embodiment is a drive 22 provided by a distance 32 between the imaging optics 3 and the container 40 is changeable. The change in distance serves to focus the sample 100 with the imaging optics 3 , For this purpose, in the embodiment shown is also an auto-focus device 42 in the module 2 provided, which with the drive 22 and the image detector 4 interacts. In modifications, the autofocus device 42 be realized as part of an external control of the device according to the invention. The change of the distance 32 happens here by movement of the container 40 relative to the module 2 , In this embodiment, of course, an optically polarizing element 13 and a polarizing filter 14 , as in 1 shown, or an optical filter 15 , as in 2 shown to be used.

In the schematically illustrated embodiment, the drive engages 22 on the side of the container 40 at. It is of course equally possible that the drive in other configurations on the module 2 facing container wall 41 attacks.

4 shows a further schematic representation of the device according to the invention 1 , which is largely the representation in 3 equivalent. In contrast to the embodiment of 3 takes place in the embodiment of 4 a change of distance 32 between imaging optics 3 and containers 40 by movement of the imaging optics 3 relative to the module 2 ; to perform this movement is a drive 22 intended.

5 shows an embodiment of the device according to the invention 1 in which by a drive 22 a configuration of the imaging optics 3 can be changed. In 5 are three optical elements 36 . 37 . 38 the imaging optics 3 shown, the optical elements 36 . 37 . 38 through the drive 22 can be moved against each other. In this way, the imaging properties of the imaging optics 3 in particular, the sample can be varied 100 through the imaging optics 3 be focused. Also in the embodiment shown here is an autofocus device 42 provided which part of the module 2 is. It would also be conceivable to carry out the focusing by means of an external regulation or also externally by a user. Of course, there is a change in the configuration of the imaging optics 3 not limited to the movement of three optical elements. Likewise, any other number of optical elements of the imaging optics 3 to be moved.

6 shows a specific embodiment of the device according to the invention 1 in perspective view. The module 2 comprises several carriers, in the illustrated embodiment, these are a first carrier 21a , a second carrier 21b , and a third carrier 21c , The carriers 21a . 21b . 21c are doing along one direction 45 from the module 2 to the container 40 arranged one behind the other. The first carrier 21a includes illumination light sources 6 for illuminating a sample (not shown here) in the container 40 , as well as a diffuser 10 to homogenize the illumination of the sample. The second carrier 21b includes the imaging optics 3 and the image detector 4 , The third carrier 21c includes the optical system 5 for detecting the optical behavior of the at least one sensor.

In the embodiment of 6 are two sensor spots 30 in the container 40 provided accordingly includes the optical system 5 a first subsystem 5a and a second subsystem 5b In this embodiment, each subsystem 5a . 5b with exactly one sensor spot 30 interacts. Each subsystem 5a . 5b has an excitation light source 7 , a photodetector 8th and a reference light source 60 all of which have already been discussed above. So that each of the subsystems 5a . 5b with one of the sensor spots 30 can interact, is in each case a light guide 70 provided, each having an optical connection between a subsystem 5a . 5b and a sensor spot 30 manufactures. In modifications, a subsystem of the optical system may also interact with more than one sensor. Likewise, an optical fiber may make an optical connection between a plurality of sensor spots and the optical system, wherein the optical system may in turn comprise one or more subsystems. Furthermore, the carriers 21a . 21b . 21c also be arranged in a different order.

In the individual carriers 21a . 21b and 21c are breakthroughs 71 for the light guides 70 and the beam path 31 the imaging optics 3 intended.

7 shows an embodiment of the device according to the invention 1 similar to the one in 4 shown. In the 7 however, is additionally an illumination light source 6 shown, as well as a control device 43 for the illumination light source 6 , About the control device 43 can the lighting of the sample 100 adapted to the particular requirements of an investigation. For example, the intensity of the illumination light can be set, or a time profile of the intensity of the illumination light can be set, which also includes the delivery of illumination pulses by the illumination light source 6 includes. Furthermore, the device 1 a reflector 50 on which one on the module 2 opposite side of the container 40 is appropriate. Such a reflector 50 is particularly advantageous to light from the illumination light source 6 into the sample 100 to reflect back, and so the illumination of the sample 100 to improve. The use of a reflector 50 is not limited to the embodiment shown. Such a reflector can be used in any embodiment of the invention. Often, in investigations for which the device according to the invention 1 can be used, a cover of the container 40 required. Then it lends itself to the interior of the container 40 reflective side of the cover form, so that the cover of the container 40 as a reflector 50 serves.

8th shows an embodiment of the device according to the invention, which a plurality of containers 40 , in the embodiment shown twenty-four, which in a matrix-like manner in a base plate 90 are arranged. In the base plate 90 installed, and therefore not visible here, are the modules 2 ; it can be a module 2 one or more containers 40 be assigned. The data of all modules becomes advantageous 2 , So at least the captured images and the detected optical behavior of the in the respective containers 40 used sensors inside the base plate 90 detected by appropriate electronic devices and preferably a single interface 91 provided for a user. For example, the data via the interface 91 to an external processing device 95 be transmitted. The transmission can be wireless or wired, corresponding possibilities of data transmission are known in the art. the interface 91 can also be used to control signals from an external control system 96 to the device 1 to convey. For this purpose, but also, as shown here, another interface 92 to be available. The processing device 95 can make an evaluation of the data in order to conclude about the optical behavior of the sensors used to appropriate variables of the respective samples. But it is also possible, such processing steps already within each module 2 or inside the base plate 90 perform only their results to the external processing device 95 be transmitted. In the external processing device 95 then further processing steps can take place, as non-limiting examples may be mentioned as a graphical representation or a record of the time course of the transmitted data.

Depending on the measurement task can be in all containers 40 the device 1 similar sensors 30 located, or at least two containers 40 may be in terms of the sensors used 30 differ.

In a device 1 like in the 8th can show a common cover for the containers 40 be provided, in the embodiment shown approximately in the manner of a rectangular lid. Here then can the containers 40 facing side of the cover to be reflective to a reflector 50 of the type discussed above.

9 schematically shows a further embodiment of the device according to the invention 1 , A module 2 In this embodiment, for example, two containers 40 assigned. In every container 40 are a sample 100 , and in the embodiment shown two sensor spots 30 , The module 2 includes an imaging optic 3 , those who both samples 100 on an image detector 4 maps. In the illustration behind the image detector 4 arranged and dashed lines is the optical system 5 for detecting the optical behavior of the sensors 30 , The optical system 5 here includes a first subsystem 5a and a second subsystem 5b where each subsystem 5a . 5b the optical behavior of the sensors 30 in one of the two containers 40 detected.

It is not excluded that the imaging optics 3 Includes components, each for each container 40 , and thus for each sample to be imaged 100 , are available separately. Likewise, the imaging optics 3 Components include that for imaging each of the samples 100 be used.

In other embodiments, a module 2 also more than two containers 40 be assigned. It should again be emphasized that the module 2 not from container 40 to container 40 is moved.

The invention has been described with reference to preferred embodiments. It will be obvious to those skilled in the art that modifications of the embodiments are possible without departing from the scope of the following claims.

QUOTES INCLUDE IN THE DESCRIPTION

This list of the documents listed by the applicant has been generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Cited patent literature

• DE 19949029 C2 [0004]
• EP 1811017 A1 [0005]

Cited non-patent literature

• "Automated Multiparametric Platform for High-Content and High-Throughput Analytical Screening on Living Cells" by Thomas Geisler, Johann Ressler, Hartmann Harz, Bernhard Wolf and Rainer Uhl [0003]

Claims (25)

Contraption ( 1 ) for capturing at least one image of at least one sample ( 100 ) and / or for detecting at least one variable of the at least one sample ( 100 ), with at least one container ( 40 ) for the at least one sample ( 100 ), and with at least one sensor ( 30 ) in the container ( 40 ), whereby the sensor ( 30 ) shows an optical behavior dependent on the at least one variable, characterized in that at least one module ( 2 ), each module ( 2 ) at least one container ( 40 ) and with each module ( 2 ) at least one image of the sample ( 100 ) and the optical behavior of each sensor ( 30 ) in the at least one container ( 40 ), to which it is assigned, are detectable. Device according to claim 1, wherein the module ( 2 ) an image detector ( 4 ) for capturing an image of the sample ( 100 ), an imaging optics associated therewith ( 3 ) and an optical system ( 5 ) for detecting the optical behavior of each sensor ( 30 ) having. Apparatus according to claim 1 or 2, wherein the at least one sensor as a sensor spot ( 30 ) formed at a position within the container ( 40 ) is fixed. Device according to one of the preceding claims, wherein in the module ( 2 ) at least one illumination light source ( 6 ) for illuminating the respective sample ( 100 ) is provided in the image acquisition. Contraption ( 1 ) according to one of claims 2 to 4, wherein the optical behavior of at least one sensor ( 30 ) is a luminescent phenomenon, and the optical system ( 5 ) for detecting the optical behavior of the sensor ( 30 ) at least one excitation light source ( 7 ) for excitation of the luminescence phenomenon and a detector ( 8th ) for detecting the luminescence phenomenon. Contraption ( 1 ) according to one of claims 2 to 5, wherein the imaging optics ( 3 ) a lens ( 9 ) with variable focal length. Contraption ( 1 ) according to claim 6, wherein the lens ( 9 ) variable focal length is a liquid lens. Contraption ( 1 ) according to one of claims 2 to 7, wherein by a drive ( 22 ) a configuration of the imaging optics ( 3 ) and / or a distance ( 32 ) between the imaging optics ( 3 ) and a respective container ( 40 ) is changeable. Contraption ( 1 ) according to one of claims 6 to 8, wherein the module ( 2 ) an autofocus device ( 42 ) for the imaging optics ( 3 ) having. Contraption ( 1 ) according to one of claims 4 to 9, wherein the module ( 2 ) a control device ( 43 ) of the at least one illumination light source ( 6 ) having. Contraption ( 1 ) according to one of the preceding claims, wherein at least one container ( 40 ) a reflector ( 50 ) on a module ( 2 ) opposite side of the container ( 40 ) assigned. Contraption ( 1 ) according to any one of the preceding claims for use in an incubator. Contraption ( 1 ) according to one of claims 2 to 12, wherein in a beam path ( 31 ) of the imaging optics ( 3 ) and / or in a beam path ( 32 ) of the optical system ( 5 ) an optically polarizing element ( 13 ) and a polarizing filter ( 14 ) are provided. Contraption ( 1 ) according to one of claims 2 to 13, wherein in a beam path ( 31 ) of the imaging optics ( 3 ) and / or in a beam path ( 32 ) of the optical system ( 5 ) optical filters ( 15 ) are provided with a wavelength-dependent transmission behavior. Contraption ( 1 ) according to one of claims 2 to 14, wherein the optical system ( 5 ) at least one light guide ( 70 ) for detecting the optical behavior of at least one sensor ( 30 ) having. Contraption ( 1 ) according to one of claims 2 to 15, wherein the module ( 2 ) several carriers ( 21a . 21b . 21c ), and the illumination light source ( 6 ), the image detector ( 4 ) and the optical system ( 5 ) within the module ( 2 ) on the various carriers ( 21a . 21b . 21c ) are arranged. Contraption ( 1 ) according to one of the preceding claims, wherein the at least one variable, of which the optical behavior of the at least one sensor ( 30 ), is a temperature, a pressure, a substance concentration, an ion concentration, a pH or a partial pressure of a gas. Contraption ( 1 ) according to any one of the preceding claims, comprising a plurality of containers ( 40 ), and an interface ( 91 ), by means of the acquired data of all modules ( 2 ) are readable. Method for detecting at least one image of at least one sample ( 100 ) and / or to Detecting at least one variable of the at least one sample ( 100 ), comprising the following steps: a) assigning at least one sensor ( 30 ), which shows an optical behavior dependent on the at least one variable, for each sample ( 100 ); b) forming a fixed assignment of each sample ( 100 ) to a module ( 2 ), which has an image detector ( 4 ) and an imaging optics associated therewith ( 3 ), wherein a module ( 2 ) one or more samples ( 100 ) are assigned permanently; c) capturing at least one image of each sample ( 100 ) with the module ( 2 ) to which the respective sample ( 100 ) is permanently assigned; d) detecting the optical behavior of the at least one of each sample ( 100 ) associated sensor ( 30 ) with the module ( 2 ) to which the respective sample ( 100 ) and which for this purpose is an optical system ( 5 ); and e) transmitting the at least one image and / or the optical behavior of the at least one sensor ( 30 ) to a processing device ( 46 . 95 ). Method according to Claim 19, wherein step c and / or step d are carried out several times in succession. Method according to claim 19 or 20, wherein at least one module ( 2 ) at least two illumination light sources ( 6 ) for illuminating the respective sample ( 100 ), which are activated in a time change, so that, depending on the lighting situation, different images of the sample ( 100 ). The method of any of claims 19 to 21, wherein steps c and d are performed for a plurality of samples. Method according to one of claims 19 to 22, wherein the imaging optics ( 3 ) and / or the image detector ( 4 ) and / or the optical system ( 5 ) and / or at least one illumination light source ( 6 ) and or at least one excitation light source ( 7 ) for exciting a luminescence of the at least one sensor ( 30 ) by an external control system ( 96 ) be managed. Method according to one of claims 19 to 23, wherein the at least one sample ( 100 ) contains a cell culture. Method according to claim 24, wherein, by detecting at least one image of the at least one sample ( 100 Information about the cell morphology and / or cell vitality and / or cell growth are obtained, and wherein by detecting the at least one variable information about the environmental conditions of the cell culture and / or about the metabolism of the cell culture are obtained.

Images