System for the simultaneous thermal analysis of a large number of individual samples of a material, in particular a biological one, by dynamic differential scanning calorimetry (DSC), sample carrier and method for the simultaneous analysis of a large number of individual samples

Abstract

The present invention provides a system for the simultaneous thermal analysis of a plurality of individual samples of a material, in particular a biological one, by dynamic differential scanning calorimetry (DSC), comprising at least one sample carrier having a plurality of sample vessels, each sample vessel being assigned an individual sensor for measuring the amount of heat emitted or absorbed by the individual sample during the thermal analysis; a heating and / or cooling unit for the simultaneous application of temperature to the individual samples contained in the sample vessels, comprising a receptacle for the at least one sample carrier;a measuring device which is connected to the individual sensors and is designed to simultaneously record a measured value for the amount of heat released or absorbed by the individual samples during the thermal analysis, a sample carrier, in particular for use in this system, and a method for the simultaneous analysis of a plurality of individual samples or groups of individual samples by dynamic differential scanning calorimetry (DSC).;

Description

[0001] The present invention relates to a system for the simultaneous thermal analysis of a plurality of individual samples of a material, in particular a biological material, by dynamic differential scanning calorimetry (DSC), a sample carrier, in particular for use in such a system, and a method for the simultaneous analysis of a plurality of individual samples.

[0002] Differential scanning calorimetry (DSC) is a thermal analysis method for measuring the amount of heat released or absorbed by a sample during heating, cooling, or an isothermal process. Differential scanning calorimetry can be used for a variety of analyses, such as the analysis of melting and glass transition temperatures, the degree of crystallization, the kinetics of chemical reactions, specific heat capacity, and phase transitions. Differential scanning calorimetry (DSC) also allows analyses to be used to detect diseases and in medical research. Typically, measuring equipment for conducting analyses using differential scanning calorimetry only allows the simultaneous analysis of a few samples or individual samples.With high sample throughput and due to the limited capacity for analyses per unit of time, waiting times for required analyses are particularly long. Furthermore, analyses cannot be carried out on an economical scale because measuring individual samples is correspondingly time-consuming. Furthermore, conventional measuring equipment requires large sample volumes of 15 µl or more to perform reproducible measurements. Therefore, existing measuring equipment is not economically viable in the commercial sector.

[0003] Devices and methods are known that are typically used for research purposes.

[0004] US 2019 / 0003995 A1 describes a dynamic differential scanning calorimeter device for detecting diseases and monitoring therapeutic efficacy by detecting heat-stable variants of proteins and / or metabolites in biological samples.

[0005] WO 2017 / 066800 A1 describes methods for characterizing and / or predicting risk associated with a biological sample using thermal stability profiles.

[0006] DE 101 06 118 A1, DE 101 43 517 A1, DE 10 2016 117 754 A1, US 2009 / 0 031 826 A1, US 4 350 446 A, DE 10 2007 005 618 A1 and DE 101 37 954 A1 disclose systems for the simultaneous thermal analysis of a plurality of individual samples with sensors assigned to the samples and a heating unit for the simultaneous application of temperature, as well as measuring devices which record the values measured by the sensors.

[0007] The object of the present invention is to provide possibilities for carrying out analyses using dynamic differential calorimetry in a more cost-effective, simpler and faster manner.

[0008] According to the invention, this object is achieved by the subject matter of the independent claims.

[0009] According to a first aspect of the invention, a system for the simultaneous thermal analysis of a plurality of individual samples of a material, in particular a biological one, by dynamic differential scanning calorimetry (DSC) is provided. The system comprises at least one sample carrier having a plurality of sample vessels, each sample vessel being assigned an individual sensor for measuring the amount of heat released or absorbed by the individual sample during the thermal analysis, a heating and / or cooling unit for the simultaneous temperature application to the individual samples contained in the sample vessels, with a receptacle for the at least one sample carrier, a measuring device which is connected to the individual sensors and is designed to simultaneously record a measured value for the amount of heat released or absorbed by the individual samples during the thermal analysis.

[0010] According to a second aspect of the invention, a sample carrier is provided, in particular for use in the aforementioned system, wherein the sample carrier has a plurality of sample vessels, preferably arranged in a defined grid, each for an individual sample.

[0011] According to a third aspect of the invention, a method is provided for the simultaneous analysis of a plurality of individual samples or groups of individual samples of a material, in particular a biological material, by dynamic differential scanning calorimetry (DSC) in an aforementioned system.The method comprises the following steps: Placing the individual samples in sample vessels in a sample carrier as described above, with individual sensors assigned to the respective sample vessel, Placing the sample carrier in a heating and / or cooling unit, Connecting the individual sensors to a measuring device, Carrying out a thermal analysis with simultaneous measurement of the amount of heat released or absorbed by the individual samples during the thermal analysis by the individual sensors, Simultaneous recording of measured values of the individual samples or groups of individual samples by the measuring device, Sending the measured values to an evaluation unit that communicates with the measuring device and simultaneous evaluation of the measured values and deriving characterizing data structures of the individual samples or groups of individual samples on the basis of the measured values by means of the evaluation unit.

[0012] According to a fourth aspect of the invention, the use of a system according to the invention and / or a sample carrier according to the invention for the simultaneous thermal and / or visual analysis of, in particular, biological individual samples by dynamic differential scanning calorimetry (DSC) is provided.

[0013] One idea underlying the present invention is to perform reproducible measurements, even of small sample volumes, with high sample throughput, while simultaneously reducing the time required for sample preparation and analysis of the measurement results. The invention can accelerate product development cycles, particularly, but not limited to, biotechnological development, and shorten waiting times for analysis results, particularly in medical diagnostics. The proposed invention also allows the simultaneous analysis of multiple samples under the same analysis conditions and the derivation of differentiated measurement and analysis results.

[0014] Advantageous embodiments and further developments emerge from the subclaims which refer back to the independent claims and from the description with reference to the figures.

[0015] According to one embodiment of the system, the receptacle is arranged in a test chamber, wherein the ambient conditions within the test chamber are defined or variably controllable. This allows the simultaneous analysis of several samples in one measurement cycle and under the same ambient or measurement conditions or under the same variation of the environmental conditions, for example, during the course of an analysis. This offers advantages in terms of sample throughput but also with regard to the reproducibility of the measurement results and allows the simultaneous analysis of several similar sample series under identical conditions. In this context, the defined or variably controllable ambient conditions within the test chamber are selected in particular from: temperature, pressure, relative humidity, (inert) gas atmosphere and combinations thereof.

[0016] According to a further development, the system according to the invention further includes an evaluation unit configured to receive the measured values from the measuring device, analyze them, and estimate characterizing data structures based on the measured values for each individual sample. The system thus allows for the simultaneous derivation of data structures from measured values of individual samples that were acquired under identical conditions and are thus fully comparable with regard to all parameters. This enables and improves the achievement of reproducibility across a large number of measurements and samples.

[0017] According to a further development, the system includes a display designed to visualize measured values and / or data structures. The direct representation of the analysis process and the recorded measured values and / or data structures is thus significantly simplified and allows the system user real-time monitoring of the analysis and the recorded measured values before or after evaluation, as well as the direct display and comparison of the measured values and analysis results. This also offers advantages from a quality control perspective and can contribute to increased efficiency in system use. The display can also be used to show the analysis parameters. If the display is designed as a touchscreen, for example, it serves simultaneously for system control and for entering or selecting analysis parameters or analysis programs of the system.

[0018] According to the invention, the individual sensors are combined in a sensor plate. The number of individual sensors in the sensor plate corresponds to the number of sample vessels in the sample carrier. The individual sensors are arranged in the sensor plate at positions corresponding to the sample vessels. The use of a sensor plate contributes to simplifying the system and improving the positioning of the sensors combined in the sensor plate and fixed at defined, standardizable positions in the sensor plate relative to the sample or sample vessel. This also ensures consistently high quality of the measurement results, as the positioning accuracy and positional fidelity of the sensors are guaranteed.

[0019] In this context, the system according to the invention provides that the sensor plate is provided as a separate element that can be connected to the sample carrier in a form-fitting or force-fitting manner. The sensor plate can thus be easily connected to the sample carrier, for example, by plugging it onto it, locking it into place, or connecting it to the sample carrier using a clip connection or the like. The measurement or the measures preparatory to the measurement, such as sample preparation or preparation of the sample carrier, are thereby significantly accelerated and positioning is improved and reproducible. The data lines connected to the sensors can also be combined in the sensor plate and integrated into the system via a connection, for example a plug-in connection.

[0020] According to a further alternative embodiment of the system, the sensor plate is designed as an element permanently arranged in the holder and remains there. To perform the measurement, the sample carrier only needs to be placed, plugged, or latched or clipped onto the sensor plate, which is preferably fixed in the holder. Because the sensor plate remains permanently in the holder and thus in the system, positioning the sample carrier is considerably easier and faster. Since the sensor plate does not come into direct contact with the sample, there is no risk of contamination or cross-contamination within the system. There is also no need to clean or laboriously sterilize the sensor plate after the measurement, which increases the user-friendliness of the system and can increase the sample throughput per unit of time.

[0021] According to a further alternative embodiment of the system according to the invention, an individual sensor is provided that is integrated into each sample vessel or that can be positively or non-positively connected to each sample vessel. This allows for individual control of each sample vessel. This embodiment also allows for the evaluation of partially filled sample carriers.

[0022] According to a further embodiment, a base area of the individual sensor essentially corresponds to a base area of the sample vessel. This ensures that measured values are recorded across the entire base area of the sample vessel, thus significantly increasing measurement accuracy.

[0023] According to a further embodiment, the evaluation unit further comprises an interface or communication interface which is designed to establish a communication connection between the evaluation unit and an external communication participant. This enables the evaluation unit to transmit data records from the system, in particular to data storage devices such as a cloud or the like, or to servers without itself being communicatively coupled to a server or the like. In this way, the data can be transmitted more easily and, if necessary, protected during transmission. The interface can be designed as an interface for wired or wireless data transmission. Transmission, for example, via Bluetooth, a WLAN connection or another communication standard familiar to those skilled in the art is possible and encompassed by the invention.

[0024] According to a further development, the system further comprises an illumination unit, wherein the illumination unit is selected from: a UV light illumination unit, a illumination unit designed to emit visible light, a illumination unit designed to emit infrared light, a illumination unit designed to emit polarized light, and a illumination unit designed to emit fluorescent light, in particular blue, green, or red fluorescent light. The system thus enables simultaneous spectral analysis of the samples during the thermal analysis and expands the measurement and data spectrum that can be acquired with the system. Processes within the sample can also be visually recorded or made visible during the thermal analysis.

[0025] According to a further embodiment of the system, the heating and / or cooling unit, the receptacle for the at least one sample carrier, the measuring device, the evaluation unit, the test chamber, the lighting unit, and / or the display are at least partially enclosed by a housing, in particular a common housing. Thus, the system, or at least components of the system, are compactly combined into a single unit, and the design of a portable system is also enabled.

[0026] According to a further embodiment of the system, an interface and / or a viewing window is provided for arranging an optical evaluation device, in particular a camera device, a microscope device, a fluorescence microscope, or a Raman device. This enables a visual inspection of the analysis process and an optical analysis of the samples, thus improving the evaluation of the measurement results and expanding the range of analysis methods that can be performed with the system, particularly in conjunction with and using the previously described illumination unit and the illumination options provided thereby.

[0027] According to a further embodiment of the system, the interface and / or the viewing window are integrated into the housing and / or the test chamber. The integration of the interface enables simple and rapid connection of the system to third-party devices and the connection of optical evaluation devices, while the viewing window provides direct optical access to the samples and allows visual evaluation, for example, using a camera or microscope.

[0028] According to the invention, the sample carrier is designed as a microtiter plate with a standardized configuration. In a further development, the receptacle is designed as an insert compartment for the microtiter plate. This enables high sample throughput, while the microtiter plate, depending on its configuration, also allows the measurement of small volumes, in particular less than 10 µl of sample volume in the individual sample. The insert compartment significantly improves the user-friendliness of the system, as a reproducible positioning of the microtiter plate in the system can be carried out before each measurement.

[0029] According to a further development of the sample carrier, it is designed as a standardized microtiter plate made of a temperature-resistant material, in particular plastic, with between 6 and 1546 sample vessels. This enables the simultaneous measurement of a large number of samples with high reproducibility, thereby significantly increasing sample throughput. Furthermore, the use of standardized microtiter plates, for example in the laboratory-typical, so-called 96-well microtiter plate format, allows the previously described sensor plate to be connected to it in a similarly standardized design. This simplifies the precise positioning of the measuring sensors relative to the sample vessels in the microtiter plate. Sample preparation, which can also be carried out automatically due to the standard format of the sample carrier, is also significantly accelerated, with corresponding advantages for sample throughput.The standardized microtiter plate can also be inserted into appropriately matched receptacles in the measurement system, allowing the system to be quickly and easily loaded with a variety of samples. After the analysis is complete, the microtiter plate can be discarded or cleaned and reused, making the system immediately available for the next measurement.

[0030] According to a further embodiment of the sample carrier, the plastic material is temperature-resistant in a temperature range between -200°C and +250°C, preferably between -80°C and +200°C. This allows measurement in a high temperature range without any impairment of the sample carrier during the measurement. Furthermore, it is also possible to use sample carriers coming directly from cryogenic storage for the measurement. This allows a large number of samples to be prepared for measurement, stored at extremely low temperatures, for example -80°C, and then processed in the system without any further preparatory steps being necessary before the respective analysis or measurement. This increases the efficiency of the system and the sample throughput.

[0031] The sample carrier can be configured to assign an individual sensor to each sample vessel for measuring the amount of heat released or absorbed by the individual samples during a thermal analysis. The system thus operates with a multitude of individual sensors that perform measurements simultaneously. The clear assignment of the individual sensor to a sample vessel ensures that the sensor only measures the respective individual sample. The individual sensors are sufficiently miniaturized so that measured values from individual samples in the previously described microtiter plates can be reliably and reproducibly recorded, even in the smallest measurement volumes.

[0032] According to a further embodiment, the individual sensors are combined in a sensor plate, and the number of individual sensors on the sensor plate corresponds to the number of sample vessels in the sample carrier. The individual sensors are arranged in positions on the sensor plate that correspond to the sample vessels. The use of a sensor plate significantly simplifies the handling of the system, since the sensor plate, whose base area and arrangement of the sensors corresponds to the configuration of the sample carrier and the arrangement of the sample vessels provided there, can be connected to the sample carrier before the measurement. The connection can be made, for example, by plugging, locking, clipping, or in any other suitable manner to form a positive or non-positive connection.The connection between the sensor plate and the sample carrier features a high degree of positioning accuracy, ensuring that the samples contained in the sample vessels are measured reproducibly and with high precision. After the analysis is complete, the sensor plate can be easily separated from the sample carrier and prepared for the next measurement. This provides a modular system that can be used highly efficiently and to process high sample throughput, thus realizing time and cost savings.

[0033] According to one embodiment of the method, the analysis is carried out under defined or variably controllable environmental conditions. The environmental conditions are selected from temperature, pressure, relative humidity, (inert) gas atmosphere and combinations thereof. The method provides that the environmental conditions are kept constant by the system during the measurement, or that corresponding profiles for the environmental conditions, e.g. a variable temperature, variable pressure, a variation in the air humidity or the gas atmosphere, are generated in the system, whereby the behavior of the samples under varying parameters of the environmental conditions can be measured. The respective environmental conditions in the system are monitored by suitable sensors, which are arranged, for example, in the test chamber or the housing as described above.The ambient conditions can also be displayed on the previously described display or integrated into the data sets to ensure complete traceability and / or reproducibility of the measurement.

[0034] According to a further development of the method, this further comprises a visual analysis of the individual samples or groups of individual samples using an optical evaluation device, in particular a camera device, a microscope device, a fluorescence microscope, or a Raman device. In addition to or as an alternative to the acquisition of the measured values via the sensors described above, a visual evaluation of the samples can also be carried out during the analysis process, which allows additional conclusions to be drawn about the composition of the sample or the behavior of the sampled materials during the thermal analysis. The visual inspection of the individual samples or groups of individual samples is preferably carried out via the interface described above or a corresponding viewing window in the test chamber or the housing of the system.It is also possible for the system to automatically capture visual measurement values, and for the corresponding data sets to be output by the system in combination with the data sets captured by the sensors. The combination of captured sensor values and additionally or alternatively captured visual parameters of the samples increases the flexibility and thus the range of applications of the system, which can thus be easily adapted or deployed for various measurement tasks.

[0035] A further development of the method provides for the analysis to be carried out within a defined temperature profile. Using the previously described variation of the ambient conditions, this can be carried out simply and reproducibly, and controlled automatically or manually.

[0036] In a preferred embodiment of the method according to the invention, simultaneous evaluation of the individual samples in the evaluation unit is carried out automatically or manually. By thermally analyzing a large number of individual samples simultaneously in the system according to the invention, the sample throughput can be significantly increased and the efficiency of the system improved. Thus, a large number of data sets can be made available, which, with automated evaluation, allow direct conclusions to be drawn about the sample behavior or composition of the samples. Comparisons between different samples are thus made possible in a single measurement or analysis run. The option for manual evaluation allows the user to adjust parameters during the analysis or for the subsequent analysis process.The system provides appropriate software for this purpose, which records and simultaneously evaluates all measurements performed in parallel. The software can be connected to an integrated database, enabling fully automated evaluations. Manual evaluation is also possible in parallel or as an alternative. During the measurement, each sample can be optically analyzed in addition to or as an alternative. The corresponding measured values are also recorded automatically or manually and evaluated, preferably with software support.

[0037] In a further development, the method further comprises the step of visualizing the data structures, particularly on a display. This allows the analysis to be tracked in real time, with the recorded measured values additionally being forwarded to a subsequent evaluation instance via the previously described interface. Visualizing the data structures on a display also allows measurement errors or system malfunctions to be quickly identified.

[0038] The above embodiments and further developments can be combined with one another as desired, where appropriate. Further possible embodiments, further developments, and implementations of the invention also include combinations of features of the invention not explicitly mentioned above or described below with respect to the exemplary embodiments. In particular, those skilled in the art will also add individual aspects as improvements or additions to the respective basic form of the present invention.

[0039] The present invention will be explained in more detail below using exemplary embodiments with reference to the accompanying figures of the drawings. The figures show: Fig. 1 a schematic representation of a sample carrier according to an embodiment of the invention in plan view; Fig. 2 a schematic representation of a further embodiment of the sample carrier according to a further embodiment of the invention in side view; Fig. 3 a schematic representation of a system according to an embodiment of the invention in perspective view; and Fig. 4 a flowchart of a method for the analysis, in particular for the analysis by dynamic differential scanning calorimetry (DSC), of biological material, according to an embodiment of the invention.

[0040] In the figures of the drawing, identical, functionally identical and acting elements, features and components are provided with the same reference symbols, unless otherwise stated.

[0041] Although specific embodiments and modifications are illustrated and described herein, those skilled in the art will appreciate that a variety of alternative and / or similar embodiments may be substituted for the specific embodiments illustrated and described without departing from the scope of the present invention. This application is generally intended to cover all modifications or variations of the specific embodiments described herein.

[0042] The accompanying figures are intended to provide a further understanding of embodiments of the invention and, in conjunction with the description, serve to explain principles and concepts of the invention. Other embodiments and many of the noted advantages will be apparent upon reference to the drawings. The drawings are to be understood as schematic drawings only, and elements of the drawings are not necessarily to scale. Directional terminology such as "top", "bottom", "left", "right", "above", "below", "horizontal", "vertical", "front", "rear" and similar terms are used for purposes of explanation only and are not intended to limit generality to specific embodiments shown in the figures.

[0043] Dashed lines in the figures of the drawings illustrate that the connections between the components connecting the dashed lines do not necessarily have to have physical contact with each other, but can equally be wirelessly coupled to each other.

[0044] Fig. 1 shows a schematic representation of a sample carrier 10 according to an embodiment of the invention in plan view. The sample carrier 10 shown here is a microtiter plate 14 with a total of 56 individual sample vessels 11, which are arranged in a standardized grid in the microtiter plate 14. The sample carrier 10 is of course not limited to the embodiments and configuration shown here. Likewise, microtiter plates 14 with fewer or more sample vessels 11 can also be used in the system 20 according to the invention. The system 20 according to the invention is designed for the use of sample carriers 10 with, in particular, between 6 and 1536 sample vessels 11 and here allows a defined and reproducible measurement for each individual sample. The sample carrier 10 according to the invention allows the measurement of small volumes, i.e., samples with a sample volume of 10 µl or less.

[0045] In the system 20 according to the invention, standardized microtiter plates 14 available in the laboratory environment can thus be used. In the embodiment according to Fig. 1, the sample carrier 10 has individual sensors 12 integrated into the respective sample vessels 11. The individual sensors 12 measure the amount of heat released or absorbed by the individual samples during the thermal analysis by means of dynamic differential scanning calorimetry (DSC). Fig. The embodiment shown in Figure 1 shows an integrated sample carrier 10, i.e., the individual sensors 12 and the sample carrier 10 or the sample vessels 11 are firmly connected to one another, and the individual sensors 12 are integrated into the sample vessels 11. In an alternative embodiment not shown here, it is also possible for the individual sensors 12, in the form of sensor plates having the same base area as the sample vessels 11, to be individually detachably connected to the respective sample vessels 11, for example, by being plugged onto them, clipped onto them, or connected to them in some other way. The use of individual sensors 12 thus enables the individual, i.e., as-needed, configuration of the sample carrier 10.

[0046] Fig. Figure 2 shows a schematic representation of a further embodiment of the sample carrier 10 according to a further embodiment of the invention in side view. The individual sensors 12, which have already been described in connection with Fig. 1 are combined here in a sensor plate 13 arranged below the microtiter plate 14. This sensor plate 13 has a number of individual sensors 12 corresponding to the sample vessels 11 in the sample carrier 10, which are firmly joined into a unit, the sensor plate 13. Before carrying out a thermal analysis by means of dynamic differential calorimetry (DSC), this sensor plate 13 is connected to the sample carrier 10, in this embodiment a microtiter plate 14, and remains in this position during the measurement. The connection to the sample carrier 10 is detachable, ie the sensor plate 13 is plugged onto the sample carrier 10, locked to it, or clipped to it. The sensor plate 13 is configured in such a way that a precisely positioned arrangement on the microtiter plate 14 is possible.After the sensor plate 13 is arranged on the sample carrier 10, an individual sensor 12 is located below each sample vessel 11 and covers its entire base area G. This allows for a comprehensive measurement across the entire sample vessel 11. After the analysis is complete, the sensor plate 13 is removed from the sample carrier 10 and can immediately be reconnected to another sample carrier 10 intended for the subsequent measurement. Because the sensor plate 13 does not come into contact with the samples to be measured, but rather a measurement is taken through the sample carrier 10 or the base 15 of the sample carrier 10, there is no risk of contamination of the sensor plate 13, so that cleaning before use for the subsequent measurement can be omitted.Nevertheless, the sensor plate 13 can be made from a suitably sterilizable material, with the individual sensors 12 being embedded in the sensor plate 13 in a liquid-tight and gas-tight manner. With regard to the geometric dimension as well as the number of individual sensors 12 in the sensor plate 13, this can be adapted to various configurations of sample carriers 10, so that a suitable sensor plate 13 is always available for the respective sample carrier 10. The sample carrier 10 can, for example, be a microtiter plate 14 which can be used in a laboratory environment and which has between 6 and 1536 sample vessels 11, so-called wells. The individual sensors 12 are matched to the respective existing base area of the individual sample vessels 11. The individual sensors 12 are sufficiently miniaturized to ensure surface coverage of the sample vessels 11 orof the bottom 15 of the sample vessels 11 without being influenced in the measurement by neighboring sample vessels 11. The respective data lines (not shown) to the individual sensors 12 are also combined in the sensor plate 13, so that the sensor plate 13 has a single interface that is connected to the system 20 in order to output the recorded measured values from the system 20 and make them available to an evaluation unit 16. For the thermal analysis, the sensor plate 13 is attached to the sample carrier 10 and the entire unit consisting of sample carrier 10 and sensor plate 13 is then inserted into the system 20. Alternatively, there is also the possibility that the sensor plate 13 is already installed in the analysis system and only the sample carrier 10 with the individual samples to be measured held therein is inserted into a holder located there and only connected to the sensor plate 13 during or after this.

[0047] Fig. 3 shows a schematic representation of a system 20 according to an embodiment of the invention in perspective view. The system 20 according to the invention comprises a housing 17, which contains a test chamber 18, into which the sample carrier 10, which is filled with the samples to be analyzed, is placed. Associated with the test chamber 18, a heating or cooling unit 19 is located in the housing 17, via which a temperature application of the samples can be carried out based on defined temperature profiles. In the test chamber 18 there is a holder (not shown here) for the insertion of the sample carrier 10. The sample carrier 10 in the embodiment of the Fig. 3 is a correspondingly configured microtiter plate 14 with a plurality of sample vessels 11, which are firmly combined in the microtiter plate 14. These sample vessels 11 are filled with the respective samples before the thermal analysis and then subjected to a simultaneous thermal analysis in the system according to the invention. For this purpose, a sensor plate 13 is arranged below the sample carrier 10, as described in connection with Fig. 2 has already been described. The individual sensors 12 are assigned to the respective samples and record temperature changes in the respective sample during the thermal analysis. The sensor data are evaluated directly in the system 20. For this purpose, the system 20 comprises an evaluation unit 16, to which the sensor data is transmitted and made available for evaluation. At the same time, it is possible to forward the analysis data to a downstream evaluation instance (not shown) via the interface 21 present in the system 20 and arranged on the housing 17. This can be, for example, a computer unit with corresponding evaluation software. Due to the embodiment of the system 20 shown in the exemplary embodiment, the recorded values can also be evaluated directly using the evaluation unit 16. The evaluated results are then visually displayed on the display 22 arranged in the housing 17.The display 22 also serves to show the operating parameters of the system 20, for example a temperature change, a temperature gradient or other ambient conditions that are set in the test chamber 18 and are part of the parameters of the respective analysis method. The display 22 can also be designed as a touchscreen and used as an input means for controlling the system 20. Parameters can be changed, parameters can be entered or the measurement can be started or stopped via this display 22. In the exemplary embodiment, the display 22 is permanently connected to the housing 17; of course, it is also possible to provide a separate display 22 that is connected to the system 20 via the aforementioned interface 21. The display 22 can of course also be part of a computer unit that is also integrated in the system 20 or is designed to be connectable to the system 20.

[0048] In the exemplary embodiment, the housing 17 additionally has a viewing window 23 through which a visual inspection of the samples is possible. The visual inspection can be carried out by means of a microscope 24 or a camera device 25, a fluorescence microscope or a Raman device, which are each connected to the system 20, ie are arranged in the region of the housing 17 or on or in the housing 17. In the exemplary embodiment according to Fig. 3 an illumination unit 26, which is configured as a UV light illumination unit, an illumination unit configured to emit visible light, an illumination unit configured to emit infrared light, an illumination unit configured to emit polarized light, or an illumination unit configured to emit fluorescent light, in particular blue, green, or red fluorescent light. This illumination unit 26 supports the visual inspection of the samples during thermal analysis.

[0049] Fig.4 shows a flow diagram of a method for the simultaneous analysis of a plurality of individual samples or groups of individual samples of a particular biological material by dynamic differential scanning calorimetry (DSC), in particular in a system according to the invention as described above.The method comprises the steps of introducing 201 the individual samples into sample vessels 11 in a sample carrier 10, in particular a sample carrier 10 as previously described, with individual sensors 12 assigned to the respective sample vessel 11; introducing 202 the sample carrier 10 into a heating and / or cooling unit 19; connecting 203 the individual sensors 12 to a measuring device; carrying out 204 a thermal analysis with simultaneous measurement of the amount of heat emitted or absorbed by the individual samples during the thermal analysis by the individual sensors 12; simultaneously recording 205 measured values of the individual samples or groups of individual samples by the measuring device; sending 206 the measured values to an evaluation unit 16 that communicates with the measuring device; and simultaneously evaluating 207 the measured values and deriving characterizing data structures of the individual samples or groups of individual samples based on the measured values by means of the evaluation unit 16.The method according to the invention can be used to perform analysis by dynamic differential scanning calorimetry (DSC), particularly of biological material, such as blood, urine, sweat, or skin tissue of animal or human origin. Furthermore, other materials can also be analyzed using the method. The method is therefore not limited to use with biological material.

[0050] To introduce 201 the individual sample, it is placed or poured into a sample vessel 11. The sample vessel 11 is part of a sample carrier 10, which comprises a plurality of sample vessels 11. This sample carrier 10 can, for example, be a microtiter plate 14 with a standardized configuration and surface area; the sample can be filled or inserted, for example, by pipetting. The sample is applied to the individual sensors 12 assigned to the respective sample vessel 11. However, these are not in direct contact with the sample, but are separated from it by the sample carrier 10. Nevertheless, the sample carrier 10 is configured such that a loss-free measurement by the individual sensors 12 is possible.

[0051] To insert 202 the sample carrier 10 into a heating and / or cooling unit 19, a test chamber 18 present there is opened, and the sample carrier 10 is then inserted into a receptacle provided in the test chamber 18. After insertion, the individual sensors 12 are connected 203 to the measuring device. The individual sensors 12 can each be connected individually to the measuring device, for example via a plug connection. Alternatively, it is also possible for the respective individual sensors 12 to be combined in a plug connection, which is then connected to a corresponding interface within the test chamber 18. In an alternative embodiment, the individual sensors 12 are combined in a sensor plate 13, which additionally has the correspondingly combined lines of the individual sensors 12 and is equipped with a plug connector for connecting to the measuring device.

[0052] To perform the thermal analysis 204, the sample carrier 10 is subjected to a temperature in the test chamber 18. The exposure can follow a defined temperature profile or be maintained at a constant temperature. The temperature range can be between -200°C and +250°C, preferably between -80°C and +200°C. The system 20, as well as the sample carrier 10 and the individual sensors 12 or the sensor plate 13, are constructed of materials such that the respective upper and lower temperature ranges do not impair the measurement performance or durability of the elements. During the temperature exposure, the individual sensors 12 record the amount of heat emitted or absorbed by the individual samples during the thermal analysis and transmit this value as a sensor value to an evaluation unit 16. The method provides for simultaneous recording 205 of measured values from the individual samples or groups of individual samples by the measuring device. D.This means that a large number of individual samples can be processed in a single measurement cycle, and the method thus offers the possibility of significantly increasing sample throughput. When using a microtiter plate 14 with, for example, 96 sample vessels, 96 individual samples can be analyzed simultaneously and the associated measurement data output accordingly. Compared to conventional methods with individual sample measurements, this results in a decisive saving in capacity and time during analysis. The configuration of the system 20 ensures that reliable individual values are recorded for the respective individual samples and made available for analysis. The simultaneous analysis also allows individual or group-wise evaluation of measurement data for individual or groups of individual samples. The transmission of the measured values 206 to an evaluation unit 16, which communicates with the measuring device, takes place via an interface 21 provided in the system 20.Transmission can be done both wired and wirelessly, for example, via a Bluetooth or WLAN connection. The recorded measured values are forwarded to a downstream evaluation instance, for example, a computer equipped with appropriate software, where they are further analyzed. At the same time, a visual representation of the recorded and / or evaluated measured values can also be provided on a display 22 provided in the system 20, which can display not only the measurement results but also the operating parameters of the system 20, such as the temperature gradient in the test chamber 18. During the simultaneous evaluation 207 of the measured values and the derivation of characterizing data structures of the individual samples or groups of individual samples based on the measured values, the raw data provided by the individual sensors 12 are processed and made available for a detailed evaluation of the analysis performed.The detailed evaluation can be carried out in the evaluation unit 16 or in a downstream evaluation instance with software support or manually.

[0053] In the foregoing detailed description, various features have been combined into one or more examples for clarity of illustration. It should be understood, however, that the above description is merely illustrative and not restrictive. It is intended to cover all alternatives, modifications, and equivalents of the various features and embodiments. Many other examples will be readily apparent to those skilled in the art based on their skill in the art in light of the above description.

[0054] The embodiments were chosen and described in order to best illustrate the principles underlying the invention and their possible practical applications. This will enable those skilled in the art to optimally modify and utilize the invention and its various embodiments with respect to the intended purpose. In the claims and the description, the terms "including" and "having" are used as neutral language terms for the corresponding term "comprising." Furthermore, the use of the terms "a," "an," and "an" is not intended to exclude a plurality of features and components described in this way. List of reference symbols 10 sample carriers 11 Sample container 12 single sensors 13 Sensor plate 14 microtiter plates 15 Floor 16 Evaluation unit 17 housings 18 test chamber 19 Heating or cooling unit 20 systems 21 Interface 22 Display 23 viewing windows 24 Microscope 25 Camera setup 26 Lighting unit 201 Insertion of the individual sample 202 Inserting the sample carrier 203 Connecting the individual sensors 204 Performing a thermal analysis 205 Simultaneous recording of measured values 206 Sending the measured values 207 Simultaneous evaluation of measured values G Floor area

Claims

[1] System (20) for the simultaneous thermal analysis of a plurality of individual samples of a material, in particular a biological material, by differential scanning calorimetry (DSC), comprising: - at least one sample carrier (10) having a plurality of sample vessels (11), each sample vessel (11) being assigned an individual sensor (12) for measuring an amount of heat emitted or absorbed by the individual sample during the thermal analysis; - a heating and / or cooling unit (19) for simultaneously applying temperature to the individual samples contained in the sample vessels (11), with a receptacle for the at least one sample carrier (10); - a measuring device which is connected to the individual sensors (12) and is designed to simultaneously record a measured value for the amount of heat emitted or absorbed by the individual samples during the thermal analysis, characterized bythat the sample carrier (10) is designed as a microtiter plate (14) with a standardized configuration and the individual sensors (12) are combined in a sensor plate (13), wherein the number of individual sensors (12) of the sensor plate (13) corresponds to the number of sample vessels (11) in the sample carrier (10), and wherein the individual sensors (12) are arranged at positions in the sensor plate (13) corresponding to the positions of the sample vessels (11) and a measurement is carried out through the bottom (15) of the sample carrier (10). [2] System (20) according to claim 1, wherein the receptacle is arranged in a test chamber (18) and wherein the ambient conditions within the test chamber (18) are defined or variably controllable. [3] System (20) according to claim 2, wherein the defined or variably controllable environmental conditions within the test chamber (18) are selected from: temperature, pressure, relative humidity, (inert) gas atmosphere and combinations thereof. [4] System (20) according to one of the preceding claims, wherein an evaluation unit (16) is further provided which is designed to receive the measured values from the measuring device, to analyze them and to estimate characterizing data structures on the basis of the measured values for each individual sample. [5] System (20) according to one of the preceding claims, wherein a display (22) is further provided which is designed to visualize measured values and / or data structures. [6] System (20) according to one of the preceding claims, wherein the sensor plate (13) is provided as a separate element which can be connected to the sample carrier (10) in a form-fitting or force-fitting manner. [7] System (20) according to one of the preceding claims, wherein the sensor plate (13) is designed as an element arranged in the receptacle. [8] System (20) according to one of the preceding claims, wherein a base area of the individual sensor (12) substantially corresponds to a base area (G) of the sample vessel (11). [9] System (20) according to one of the preceding claims, wherein the evaluation unit (16) further comprises an interface (21) which is designed to establish a communication connection between the evaluation unit (16) and an external communication participant. [10] System (20) according to claim 9, wherein the external communication participant is designed as a data processing device and is communicatively coupled to the evaluation unit (16) via the interface (21). [11] System (20) according to at least one of claims 1 to 10, further comprising an illumination unit (26), wherein the illumination unit (26) is selected from: a UV light illumination unit, a illumination unit designed to emit visible light, a illumination unit designed to emit infrared light, a illumination unit designed to emit polarized light, a illumination unit designed to emit fluorescent light, in particular blue, green or red fluorescent light. [12] System (20) according to at least one of claims 1 to 11, wherein the heating and / or cooling unit (19), the receptacle for the at least one sample carrier, the measuring device, the evaluation unit (16), the test chamber (18), the lighting unit (26) and / or the display (22) are at least partially surrounded by a housing (17), in particular a common housing (17). [13] System (20) according to one of the preceding claims, wherein an interface (21) and / or a viewing window (23) is provided for arranging an optical evaluation device, in particular a camera device (25), a microscope device, a fluorescence microscope or a Raman device. [14] System (20) according to claim 12 or 13, wherein the interface (21) and / or the viewing window (23) is provided integrated into the housing (17) and / or the test chamber (18). [15] System (20) according to one of the preceding claims, wherein the receptacle is designed as an insertion compartment for the microtiter plate (14). [16] Sample carrier (10) in a system (20) according to one of the preceding claims, wherein the sample carrier (10) has a plurality of sample vessels (11) arranged in a defined grid, each for an individual sample. [17] Sample carrier (10) according to claim 16, wherein the sample carrier (10) is designed as a standardized microtiter plate (14) made of a temperature-resistant material, in particular plastic material, with between 6 and 1536 sample vessels (11). [18] Sample carrier (10) according to claim 17, wherein the plastic material has a temperature resistance in a temperature range of between -200°C and +250°C, preferably between -80°C and +200°C. [19] Sample carrier (10) according to one of claims 16 to 18, wherein each sample vessel (11) is assigned an individual sensor (12) for measuring the amount of heat released or absorbed by the individual sample during a thermal analysis. [20] Sample carrier (10) according to one of claims 16 to 19, wherein a number of individual sensors (12) corresponding to the number of sample vessels (11) are combined in a sensor plate (13) which can be connected to the sample carrier (10) in a form-fitting or force-fitting manner, and the individual sensors (12) are arranged in positions in the sensor plate (13) corresponding to the positions of the sample vessels (11). [21] Method for the simultaneous analysis of a plurality of individual samples or groups of individual samples of a material, in particular a biological material, by dynamic differential scanning calorimetry (DSC) in a system according to one of claims 1 to 15, comprising: - introducing (201) the individual samples into sample vessels (11) in a sample carrier (10) according to one of claims 16 to 20, with individual sensors (12) assigned to the respective sample vessel (11); - introducing (202) the sample carrier (10) into a heating and / or cooling unit; - connecting (203) the individual sensors (12) to a measuring device; - carrying out (204) a thermal analysis with simultaneous measurement of the amount of heat released or absorbed by the individual samples during the thermal analysis by the individual sensors (12); - simultaneous recording (205) of measured values of the individual samples or groups of individual samples by the measuring device; - sending the measured values (206) to an evaluation unit (16) which communicates with the measuring device; and - Simultaneous evaluation (207) of the measured values and derivation of characterizing data structures of the individual samples or groups of individual samples on the basis of the measured values by means of the evaluation unit (16). [22] Method according to claim 21, wherein the analysis is carried out under defined or variably controllable environmental conditions, wherein the defined or variably controllable environmental conditions are selected from: temperature, pressure, relative humidity, (inert) gas atmosphere and combinations thereof. [23] Method according to one of claims 21 or 22, further comprising a visual analysis of the individual samples or groups of individual samples by means of an optical evaluation device, in particular a camera device (25), a microscope device, a fluorescence microscope or a Raman device. [24] Method according to one of claims 21 to 23, wherein the analysis is carried out in a defined temperature profile. [25] Method according to one of claims 21 to 24, wherein the simultaneous evaluation (207) in the evaluation unit (16) is carried out automatically or manually. [26] Method according to at least one of claims 21 to 25, further comprising: visualizing the data structures, in particular on a display (22). [27] Use of a system (20) according to at least one of claims 1 to 15 and / or a sample carrier (10) according to one of claims 16 to 20 for the simultaneous thermal and / or visual analysis of, in particular, biological individual samples by dynamic differential scanning calorimetry (DSC).

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