A system, sample carrier, and method for simultaneous thermal analysis of multiple single samples, particularly biological materials, using differential scanning calorimetry (DSC).

Abstract

This invention provides a means to perform differential scanning calorimetry analysis more cost-effectively, simply, and quickly. [Solution] A system for simultaneous thermal analysis of multiple single samples, particularly biological materials, by differential scanning calorimetry (DSC) comprises a sample carrier having multiple sample containers, each sample container assigned a single sensor for measuring the amount of heat released or absorbed from a single sample during thermal analysis; a heating and / or cooling unit having a receptacle for the sample carrier and for simultaneously applying temperature load to the single samples contained in the sample containers; and a measuring instrument connected to a single sensor and configured to simultaneously acquire measured values ​​of the amount of heat released or absorbed by a single sample during thermal analysis. Furthermore, a sample carrier for use in this system and a method for simultaneously analyzing a single sample or a group of single samples by differential scanning calorimetry (DSC) are provided.

Description

Technical Field

[0001] The present invention relates to a system for simultaneously thermally analyzing a plurality of single samples, particularly biological materials, by differential scanning calorimetry (DSC), a sample carrier for use in such a system, and a method for simultaneously analyzing a plurality of single samples.

Background Art

[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 plurality of analyses, such as analysis of melting point and glass transition temperature, crystallinity, dynamic observation of chemical reactions, specific heat capacity, and analysis of phase transitions. Differential scanning calorimetry (DSC) can also be used for detection of diseases and analysis of research in the medical field. Measuring instruments for performing analysis by differential scanning calorimetry can usually only perform simultaneous analysis of a small number of samples or single samples. Therefore, when the sample throughput is high, the analysis ability per unit time may be low, and particularly the waiting time for performing necessary analysis becomes extremely long. In addition, since measurement of a single sample requires a correspondingly large amount of time, analysis cannot be economically carried out. Furthermore, conventional measuring instruments for performing reproducible measurements also require a large amount of sample of 15 μm or more. Therefore, known measuring instruments are not suitable for economic use in the commercial field.

[0003] Typically, devices and methods used for research purposes are known.

[0004] Patent Document 1 (U.S. Patent Publication No. 2019 / 0003995) describes a differential scanning calorimetry device for detecting heat-resistant variants of proteins and / or metabolites in a biological sample to monitor disease detection and treatment effects.

[0005] Patent document 2 (International Publication No. 2017 / 066800) describes a method for characterizing and / or predicting risks associated with biological samples using thermal stability profiles. [Prior art documents] [Patent Documents]

[0006] [Patent Document 1] U.S. Patent Publication No. 2019 / 0003995 [Patent Document 2] International Publication No. 2017 / 066800 Brochure [Overview of the Initiative] [Problems that the invention aims to solve]

[0007] The object of the present invention is to provide a means for performing differential scanning calorimetry analysis more cost-effectively, simply, and quickly. [Means for solving the problem]

[0008] According to the present invention, this problem is solved by the subject matter of the independent claim.

[0009] According to a first aspect of the present invention, a system is provided for simultaneous thermal analysis of multiple single samples, particularly of biological materials, by differential scanning calorimetry (DSC). The system comprises at least one sample carrier having multiple sample containers, each sample container being assigned a single sensor for measuring the amount of heat released or absorbed from a single sample during thermal analysis; a heating and / or cooling unit having a receptacle for at least one sample carrier and for simultaneously applying temperature load to the single samples contained in the sample containers; and a measuring instrument connected to a single sensor and configured to simultaneously acquire measured values ​​of the amount of heat released or absorbed by a single sample during thermal analysis.

[0010] According to a second aspect of the present invention, a sample carrier is provided for use in the system described above, the sample carrier comprising, for each single sample, a plurality of sample containers preferably arranged in a predetermined grid.

[0011] A third aspect of the present invention provides a method for simultaneously analyzing multiple single samples or groups of single samples, particularly biological materials, by differential scanning calorimetry (DSC), especially in the system described above. This method includes the steps of: introducing a single sample into a sample carrier, particularly a sample container of the sample carrier described above (each sample container is assigned a single sensor); introducing the sample carrier into a heating and / or cooling unit; connecting the single sensor to a measuring instrument; performing thermal analysis while simultaneously measuring the amount of heat emitted or absorbed by the single sample during thermal analysis using the single sensor; simultaneously acquiring measured values ​​of the single sample or group of single samples using the measuring instrument; transmitting the measured values ​​to an evaluation unit that communicates with the measuring instrument; and simultaneously evaluating the measured values ​​using the evaluation unit and estimating the characteristic data structure of the single sample or group of single samples based on the measured values.

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

[0013] The underlying idea of ​​this invention is to perform highly reproducible measurements with high sample throughput even with smaller sample volumes, while simultaneously reducing the time required for, for example, sample preparation and analysis of measurement results. This allows the invention to accelerate product development cycles, particularly in the biotechnology field (but not limited to it), and to shorten waiting times for analytical results, especially in medical diagnostics. Furthermore, the invention makes it possible to analyze multiple samples simultaneously under the same analytical conditions and derive differentiated measurement and analytical results from them.

[0014] Advantageous embodiments and further configurations will become apparent from the description with reference to the dependent claims and drawings that depend on the independent claims.

[0015] According to one embodiment of the system, the receptacle is placed inside a test chamber, and the environmental conditions inside the test chamber are defined or variably adjustable. This allows for the simultaneous analysis of multiple samples in a single measurement cycle under the same environment or measurement conditions, or, for example, while the environmental conditions are uniformly changed during the analysis process. This offers advantages not only in sample throughput but also in the reproducibility of measurement results, enabling the simultaneous analysis of multiple similar sample series under the same conditions. In this regard, the defined or variably adjustable environmental conditions inside the test chamber are selected from temperature, pressure, relative humidity, (inert) gas atmosphere, and combinations thereof.

[0016] In a further configuration, the system according to the present invention further includes an evaluation unit configured to receive measurement values ​​from a measuring instrument, analyze these measurement values, and evaluate the feature data structure based on the measurement values ​​of each single sample. This makes it possible for the system according to the present invention to simultaneously derive data structures from measurement values ​​of single samples acquired under identical conditions and therefore fully comparable with respect to all parameters. Thus, it becomes possible to achieve and improve reproducibility across a large number of measurements and samples.

[0017] In a further configuration, the system may include a display configured to visualize measured values ​​and / or data structures. This significantly simplifies the direct display of the analysis process and acquired measured values ​​and / or data structures, allowing system users to monitor and directly view the analysis and acquired measured values ​​before and after evaluation, as well as compare measured values ​​with analysis results. This offers advantages from a quality control perspective and can also contribute to improved efficiency during system use. The display can also be used to display analysis parameters. If the display is configured as a touchscreen, for example, it can also be used for system control and for inputting or selecting system analysis parameters and analysis programs.

[0018] In a further embodiment of the system, the single sensor is integrated into a sensor plate. In this case, the number of single sensors on the sensor plate corresponds to the number of sample containers in the sample carrier. In this case, the single sensor is positioned in a location corresponding to the location of the sample container on the sensor plate. The use of a sensor plate contributes to system simplification and improved positioning accuracy of the sensor, which is integrated into the sensor plate and fixed in a standardizable, predetermined position on the sensor plate (relative to the sample or sample container). This also ensures consistent high quality of measurement results because the positioning accuracy and location accuracy of the sensor are guaranteed.

[0019] In this regard, in an advantageous further embodiment of the system according to the present invention, the sensor plate is provided as a separate element that can be connected to the sample carrier either shape-fittingly or frictionally. Thus, the sensor plate can be easily connected to the sample carrier, for example, by plugging, latching, or clipping connections. This significantly speeds up measurement or measurement preparation, such as sample preparation or sample carrier preparation, and improves positioning accuracy and repeatability. Data lines connected to the sensor can also be bundled into the sensor plate and integrated into the system via connections such as plug connections.

[0020] According to an alternative further embodiment of the system, the sensor plate is envisioned as an element permanently positioned and remaining in the receptacle. To perform a measurement, the sample carrier is simply attached, inserted, latched, or clipped to the sensor plate, preferably fixed to the receptacle. The permanent retention of the sensor plate within the receptacle and thus the system makes the placement of the sample carrier significantly 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. Furthermore, since the sensor plate does not require time-consuming cleaning or sterilization after measurement, the usability of the system and the sample throughput per unit time are improved.

[0021] According to an alternative further embodiment of the system according to the present invention, a single sensor is provided integrated within each sample container, or a single sensor is provided that can be connected to each sample container by shape-fitting or frictional engagement. This makes it possible to control each sample container individually. In this embodiment, it is also possible to evaluate only partially filled sample carriers.

[0022] In a further embodiment, the surface area of ​​a single sensor substantially corresponds to the surface area of ​​the sample container. This allows measurements to be obtained over the entire surface area of ​​the sample container, thus significantly improving measurement accuracy.

[0023] According to a further embodiment, the evaluation unit further has an interface or a communication interface configured to establish a communication connection between the evaluation unit and an external communication participant. Thereby, the evaluation unit can transmit a data set from the system, particularly on a data storage such as a cloud or to a server, even if the evaluation unit itself is not communicatively connected to the server or the like. Thus, the data can be transmitted more easily and can be protected during transmission if necessary. In this case, the interface can be configured for wired or wireless data transmission. Transmission by Bluetooth (registered trademark), a WLAN connection, or other communication standards known to those skilled in the art is possible and is included in the present invention.

[0024] According to a further configuration, the system further comprises a lighting unit, and the lighting unit is selected from a UV light lighting unit, a lighting unit designed to emit visible light, a lighting unit designed to emit infrared light, a lighting unit designed to emit polarized light, and a lighting unit designed to emit fluorescence, particularly blue, green, or red fluorescence. Thereby, the system enables simultaneous spectral analysis of the sample during thermal analysis, and the measurement and data range that can be obtained by the system is expanded. Also, the processes within the sample during thermal analysis can be visually detected or visualized.

[0025] The heating and / or cooling unit, the receptacle for 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 surrounded by a housing, particularly a common housing. Thereby, the system or at least the components of the system are compactly integrated into a unit, and it is also possible to form a portable system.

[0026] According to a further embodiment of the system, an interface and / or an observation window for arranging an optical evaluation device, in particular a camera device, a microscope device, a fluorescence microscope, or a Raman device, is provided. Thereby, visual inspection of the progress of the analysis method and optical analysis of the sample become possible, improving the evaluation of the measurement results or expanding the range of analysis methods that can be implemented in the system. This applies particularly in relation to the illumination unit described above and the illumination options provided by the illumination unit.

[0027] According to a further embodiment of the system, the interface and / or the observation window is provided to be integrated with the housing and / or the test chamber. By integrating the interface, the system can be easily and quickly connected to third-party devices and optical evaluation devices, and the observation window enables direct optical access to the sample and visual evaluation by, for example, a camera device or a microscope.

[0028] According to a further embodiment, the sample carrier is configured as a microtiter plate having a standardized configuration, and the receptacle is configured as an insertion tray for the microtiter plate. Thereby, a high throughput of samples becomes possible, and the microtiter plate enables measurement of even small amounts, particularly less than 10 μl per single sample, regardless of its configuration. The insertion tray significantly improves the usability of the system because it enables reproducible positioning of the microtiter plate within the system before each measurement.

[0029] According to a further embodiment of the sample carrier, the sample carrier comprises 6 to 1546 sample containers and is configured as a standardized microtiter plate made of a heat-resistant material, particularly plastic. This enables simultaneous measurement of multiple samples with high reproducibility, significantly improving sample throughput. For example, by using a standardized microtiter plate in the form of a so-called 96-well microtiter plate commonly used in laboratories, the sensor plates described above can also be connected to each other in a similarly standardized configuration. This facilitates accurate alignment of the measurement sensor with respect to the sample containers within the microtiter plate. The standardized form of the sample carrier also significantly speeds up sample preparation, which can be automated, providing a corresponding advantage in sample throughput. The standardized microtiter plate can further be inserted into a suitable receptacle within the measurement system, allowing for quick and easy setup of multiple samples. After the analysis is complete, the microtiter plate can be discharged or washed and reused, and the system can be immediately used for the next measurement.

[0030] In a further embodiment of the sample carrier, the plastic material is heat-resistant in a temperature range of -200°C to +250°C, preferably -80°C to +200°C. This allows for measurements in a high-temperature range without damaging the sample carrier during measurement. Furthermore, it is possible to use the sample carrier directly removed from the low-temperature storage section for measurement. This allows multiple samples to be prepared for measurement, stored at a minimum temperature of, for example, -80°C, and then processed in the system, without requiring further preparation before each analysis or measurement. This improves the efficiency of the system and sample throughput.

[0031] In a further embodiment of the sample carrier, it is assumed that a single sensor for measuring the amount of heat released or absorbed from a single sample during thermal analysis is assigned to each sample container. Thus, the system operates with multiple single sensors performing measurements simultaneously. By clearly assigning the single sensors to the sample containers, it is ensured that only each single sample is measured by the sensor. In this case, since the single sensors are sufficiently small, the measurements from a single sample in the microtiter plate described above can be obtained reliably and reproducibly, even at the smallest volume.

[0032] Each single sensor is envisioned to be either integrated within the sample container or connectable to the sample container via shape-fitting or frictional engagement. This allows for the provision of a sample carrier in which a single sensor is placed in each sample container or in only one sample container. Thus, a sample carrier suitable for measurement in the system described above and appropriately prepared is provided. This sample carrier can be supplied as a consumable or as an accessory for the system.

[0033] In an alternative embodiment, each single sensor can be connected to each sample container as needed. This allows the use of standardized sample containers that can be prepared for measurement by attaching a single sensor. Sample containers, such as standardized microtiter plates, can be separated from the single sensor after use, discarded, or cleaned and reused. This improves not only the flexibility of the system but also the efficiency of measurement and therefore the sample throughput.

[0034] In a further embodiment, the single sensor is integrated into a sensor plate, and the number of single sensors on the sensor plate corresponds to the number of sample containers in the sample carrier. In this case, the single sensor is positioned in a location corresponding to the location of the sample container on the sensor plate. The use of a sensor plate greatly simplifies the handling of the system because the surface area of ​​the sensor plate and the arrangement of the sensors correspond to the configuration of the sample carrier and the arrangement of the sample containers provided therein, and the sensor plate can be connected to the sample carrier before measurement. This connection can be a shape-fit or friction-engagement connection, for example, by plugging, latching, clipping, or other appropriate method. Since the connection between the sensor plate and the sample carrier has high positional accuracy, it is ensured that the sample in the sample container is measured with reproducible high accuracy. After analysis, the sensor plate can be easily separated from the sample carrier and used immediately for the next measurement. The modular system thus provided can achieve extremely efficient high sample throughput, thereby reducing time and cost.

[0035] According to one embodiment of the method of the present invention, the analysis is performed under specified or variably adaptable environmental conditions. In this case, the environmental conditions are selected from temperature, pressure, relative humidity, (inert) gas atmosphere, and combinations thereof. In this method, the system maintains the environmental conditions constant during measurement, or a profile corresponding to the environmental conditions, i.e., changes in variable temperature, variable pressure, humidity, or gas atmosphere, is generated within the system, thereby enabling the measurement of the behavior of the sample under changing parameters of the environmental conditions. Each environmental condition within the system is monitored, for example, by appropriate sensors located in the test chamber or housing described above. The environmental conditions can be displayed on the display described above or output to be integrated into the data set, thereby ensuring complete traceability and / or reproducibility of the measurement.

[0036] A further configuration of the method according to the present invention further includes visually analyzing a single sample or a group of samples using an optical evaluation device, particularly a camera device, a microscope device, a fluorescence microscope, or a Raman device. Visual evaluation of the sample can also be performed during the analysis process as an addition to or alternative to the acquisition of measurements by the sensors described above, thereby making it possible to draw further conclusions about the composition or material behavior of the sample during thermal analysis. Visual inspection of a single sample or a group of samples is preferably performed via the interface or observation window described above in the test chamber or housing of the system. Acquisition of visual measurements can be performed automatically within the system, and a corresponding dataset can be output from the system and combined with the dataset acquired by the sensors. The combination of acquired sensor values ​​and additionally or alternatively acquired visual parameters of the sample expands the flexibility of the system, and therefore the range of applications, making the system easily adaptable to or available for different measurement tasks.

[0037] According to a further configuration of the method according to the present invention, the analysis is assumed to be carried out under a defined temperature profile. This can be carried out easily and reproducibly and can be controlled automatically or manually via the environmental condition change options described above.

[0038] According to a preferred embodiment of the method of the present invention, simultaneous evaluation of single samples is performed automatically or manually in the evaluation unit. Simultaneous thermal analysis of multiple single samples in the system according to the present invention significantly improves sample throughput and system efficiency. This allows for the provision of multiple data sets, enabling direct conclusions about the behavior or composition of the samples based on the automated evaluation. Thus, comparisons between different samples become possible in a single measurement or analysis pass. The option of manual evaluation allows the user to adjust parameters during or for subsequent analytical processes. For this purpose, the system is equipped with software that acquires and simultaneously evaluates all measurements performed in parallel. This software can connect to an integrated database, enabling fully automated evaluation. Manual evaluation can also be performed in parallel or as an alternative. Each sample may be additionally or alternatively analyzed optically during measurement. In this case, the corresponding measurements are also acquired automatically or manually and preferably evaluated with software assistance.

[0039] In a further configuration, the method according to the present invention further includes the step of visualizing the data structure, particularly on a display. This allows the analysis to be tracked in real time, and the acquired measurements are transferred to subsequent evaluation entities via the interface described above. Visualization of the data structure on the display also allows for the rapid identification of measurement errors or failures in the system.

[0040] Where appropriate, the embodiments and configurations described above can be combined as needed. Other feasible embodiments, further configurations, and implementations of the present invention also include combinations of features described above with respect to the present invention (not expressly described) or features described below with respect to exemplary embodiments. In this case, those skilled in the art will particularly add individual aspects as improvements or additions to each basic form of the present invention.

[0041] The present invention will be described in detail below based on exemplary embodiments with reference to the accompanying drawings. [Brief explanation of the drawing]

[0042] [Figure 1] This is a schematic top view showing a sample carrier according to an exemplary embodiment of the present invention. [Figure 2] A schematic side view showing a further embodiment of a sample carrier according to an exemplary further embodiment of the present invention. [Figure 3] A schematic perspective view showing a system according to an exemplary embodiment of the present invention. [Figure 4] This flowchart shows an exemplary embodiment of the present invention, specifically a method for analyzing biological materials, particularly by differential scanning calorimetry (DSC). [Modes for carrying out the invention]

[0043] Unless otherwise specified, identical elements, functionally identical elements, elements having the same function, features, and components are denoted by the same reference numeral in the drawings.

[0044] While specific embodiments and configurations are illustrated and described herein, those skilled in the art will understand that the specific embodiments illustrated and described can be replaced by a number of alternative and / or similar embodiments without departing from the scope of the invention. This application comprehensively includes all modifications or changes to the specific embodiments described herein.

[0045] The accompanying drawings facilitate a further understanding of embodiments of the present invention and serve to illustrate the principles and concepts of the invention in relation to the description herein. Other exemplary embodiments and many of the advantages described herein will become apparent with reference to the drawings. The drawings should be understood as schematic diagrams only, and the elements of the drawings are not necessarily drawn to scale. For example, terms indicating directions such as “up,” “down,” “left,” “right,” “upward,” “downward,” “horizontal,” “vertical,” “front,” and “back” are used for illustrative purposes only and do not limit the generality to the specific design shown in the drawings.

[0046] The dashed lines in the drawing indicate that the connections between the components connected by the dashed lines do not necessarily have to involve physical contact; they may also be wirelessly coupled to one another.

[0047] Figure 1 shows a top view of a sample carrier 10 according to an exemplary embodiment of the present invention. The illustrated sample carrier 10 is a microtiter plate 14 having a total of 56 single sample containers 11, these sample containers 11 arranged in a standardized grid on the microtiter plate 14. Needless to say, the sample carrier 10 is not limited to the illustrated embodiment and configuration. In the system 20 according to the present invention, a microtiter plate 14 having fewer or more sample containers 11 can also be used. The system 20 according to the present invention is particularly designed to use a sample carrier 10 having 6 to 1536 sample containers 11, which is defined for each single sample and enables reproducible measurements. The sample carrier 10 according to the present invention enables the measurement of small amounts of sample, i.e., samples with a sample volume of 10 μl or less.

[0048] Thus, in the system 20 according to the present invention, a standardized microtiter plate 14 available in a laboratory environment can be used. In the embodiment shown in Figure 1, the sample carrier 10 includes a single sensor 12 integrated within each sample container 11. The single sensor 12 measures the amount of heat emitted or absorbed from a single sample during thermal analysis by differential scanning calorimetry (DSC). In the embodiment shown in Figure 1, the integrated sample carrier 10, i.e., the single sensor 12 and the sample carrier 10 or sample container 11 are rigidly and integrally connected to each other, and the single sensor 12 is integrated within the sample container 11. The single sensor 12, in the form of a sensor plate having the same surface area as the sample container 11, can also be individually and detachably connected to each sample container 11, for example, by being inserted into the sample container 11, clipped, or connected in other ways. Thus, the use of the single sensor 12 allows for individual configurations of the sample carrier 10, i.e., configurations as needed.

[0049] Figure 2 shows a schematic side view of a further embodiment of the sample carrier 10 according to an exemplary further embodiment of the present invention. The individual sensors 12 already described in relation to Figure 1 are integrated (grouped together) in the illustrated embodiment into a sensor plate 13 located below the microtiter plate 14. This sensor plate 13 has a number of single sensors 12 corresponding to the number of sample containers 11 in the sample carrier 10, and these single sensors 12 are firmly coupled to the unit known as the sensor plate 13. Before performing thermal analysis by differential scanning calorimetry (DSC), the sensor plate 13 is connected to the sample carrier 10 (microtiter plate 14 in the illustrated exemplary embodiment) and remains in this position during measurement. In this case, the connection to the sample carrier 10 is detachable, i.e., the sensor plate 13 is inserted into, latched, or clipped to the sample carrier 10. The sensor plate 13 is configured to allow for highly accurate positional placement on the microtiter plate 14. After the sensor plate 13 is placed on the sample carrier 10, one single sensor 12 is positioned below each sample container 11, covering its surface area G. This ensures a complete measurement across the entire sample container 11. After the analysis is complete, the sensor plate 13 can be removed from the sample carrier 10 and immediately connected to another sample carrier 10 for the next measurement. Since the sensor plate 13 does not come into contact with the sample being measured and the measurement is performed via the sample carrier 10 or its bottom 15, there is no risk of contamination of the sensor plate 13, and pre-use cleaning for the next measurement can be omitted. However, the sensor plate 13 can be manufactured from a sterilizable material, in which case the single sensors 12 are embedded in the sensor plate 13 in a liquid-tight and airtight manner. The geometric dimensions of the sensor plate 13 and the number of single sensors 12 can be adjusted to suit different configurations of the sample carrier 10, so that a sensor plate 13 that fits each sample carrier 10 is always available. The sample carrier 10 may be, for example, a microtiter plate 14 that can be used in a laboratory environment and has 6 to 1536 sample containers 11 (so-called wells).In this case, the single sensor 12 is adapted to the existing surface area of ​​each single sample container 11. The single sensor 12 is small enough to reliably cover the entire surface of the sample container 11 or the bottom 15 of the sample container 11 without being affected by adjacent sample containers 11 during measurement. Data lines (not shown) to the single sensor 12 are also integrated into the sensor plate 13, so that the sensor plate 13 has a single interface connected to the system 20, thereby allowing acquired measurements to be exported from the system 20 and provided to the evaluation unit 16. For thermal analysis, the sensor plate 13 is fixed to the sample carrier 10, and the entire unit consisting of the sample carrier 10 and the sensor plate 13 is inserted into the system 20. Alternatively, the sensor plate 13 may already be installed in the analysis system, and only the sample carrier 10 containing the single sample may be inserted into the receptacle in the system and connected to the sensor plate 13 at that time or afterward.

[0050] Figure 3 shows a schematic perspective view of a system according to an exemplary embodiment of the present invention. In this case, the system 20 according to the present invention comprises a housing 17 having a test chamber 18, in which a sample carrier 10 filled with the sample to be analyzed is placed. The test chamber 18 of the housing 17 is provided with a heating or cooling unit 19, which can apply a temperature load to the sample based on a defined temperature profile. The test chamber 18 is provided with a receptacle (not shown) for inserting the sample carrier 10. In the exemplary embodiment shown in Figure 3, the sample carrier 10 is a microtiter plate 14 in which a plurality of sample containers 11 are rigidly integrated. These sample containers 11 are filled with each sample before thermal analysis and then subjected to simultaneous thermal analysis in the system according to the present invention. For this purpose, as already described in relation to Figure 2, a sensor plate 13 is located below the sample carrier 10. A single sensor 12 is assigned to each sample to acquire the temperature change of each sample during thermal analysis. The sensor data is evaluated directly within the system 20. For this purpose, the system 20 includes an evaluation unit 16 to which sensor data is transmitted and evaluated. Simultaneously, the analysis data can also be exported to a downstream evaluation entity (not shown) via an interface 21 provided in the system 20 and located on the housing 17. This could be, for example, a processing unit having corresponding evaluation software. In the exemplary embodiment of the system 20 shown, it is also possible to directly evaluate the acquired values ​​in the evaluation unit 16. The evaluation results are visually displayed on a display 22 located on the housing 17. The display 22 also displays the operating parameters of the system 20, such as temperature changes, temperature gradients, or other environmental conditions adjusted in the test chamber 18, as well as parameters belonging to each analysis method. The display 22 can also be configured as a touchscreen and can be used as an input means for controlling the system 20. Through this display 22, it is possible to change parameters, input parameters, or start or stop measurements.In the illustrated exemplary embodiment, the display 22 is rigidly connected to the housing 17, but it is of course possible to provide a separate display 22 connected to the system 20 via the interface 21 described above. The display 22 may also be part of a processing unit integrated into the system 20, or part of a processing unit configured to be connectable to the system 20.

[0051] In the illustrated exemplary embodiment, the housing 17 further has an observation window 23 through which the sample can be visually inspected. In this case, the visual inspection can be performed by a microscope 24, a camera device 25, a fluorescence microscope, or a Raman spectrometer, all of which are connected to the system 20, i.e., located in or on or inside the housing 17. In the exemplary embodiment shown in Figure 3, an illumination unit 26 is located in the test chamber 18 itself, and this illumination unit is configured as a UV light illumination unit, an illumination unit designed to emit visible light, an illumination unit designed to emit infrared light, an illumination unit designed to emit polarized light, or an illumination unit designed to emit fluorescence, particularly blue, green, or red fluorescence. This illumination unit 26 assists in the visual inspection of the sample during thermal analysis.

[0052] Figure 4 shows a flowchart of a method for simultaneously analyzing multiple single samples or groups of single samples, particularly biological materials, by differential scanning calorimetry (DSC), in the system according to the present invention described above. This method includes the steps of: introducing a single sample into a sample carrier 10, particularly a sample container 11 of the sample carrier 10 described above (each sample container 11 is assigned a single sensor 12); introducing the sample carrier 10 into a heating and / or cooling unit 19; connecting the single sensor 12 to a measuring instrument; performing thermal analysis using the single sensor 12 while simultaneously measuring the amount of heat emitted or absorbed by the single sample during thermal analysis; simultaneously acquiring measurement values ​​of the single sample or group of single samples using the measuring instrument; transmitting the measurement values ​​to an evaluation unit 16 that communicates with the measuring instrument; and simultaneously evaluating the measurement values ​​using the evaluation unit 16 and estimating the characteristic data structure of the single sample or group of single samples based on the measurement values. The method according to the present invention allows for differential scanning calorimetry (DSC) analysis, particularly for the analysis of biological materials, such as blood, urine, sweat, or skin tissue of animal or human origin. This method can also analyze other materials. Therefore, this method is not limited to use with biological materials.

[0053] In step 201, which involves introducing a single sample, the single sample is placed or filled into a sample container 11. In this case, the sample container 11 is part of a sample carrier 10 comprising multiple sample containers 11. The sample carrier 10 can be, for example, a microtiter plate 14 with a standardized configuration and surface, and the filling or placement of the sample can be performed, for example, by pipetting. In this case, the sample is applied to a single sensor 12 assigned to each sample container 11. However, these single sensors are not in direct contact with the sample and are separated by the sample carrier 10. Nevertheless, the sample carrier 10 is configured to enable lossless measurement by the single sensors 12.

[0054] In step 202, when the sample carrier 10 is introduced into the heating and / or cooling unit 19, the installed test chamber 18 is opened, and the sample carrier 10 is then inserted into a receptacle provided in the test chamber 18. Step 203, in which the single sensors 12 are connected to the measuring instrument, is performed after insertion. In this case, the single sensors 12 can be connected individually to the measuring instrument, for example, via plug connections. Alternatively, each single sensor 12 can be bundled into a plug connection and then connected to the corresponding interface in the test chamber 18. In an alternative embodiment, the single sensors 12 are integrated into a sensor plate 13, which further has bundled wires for the single sensors 12 and plug connectors for connection to the measuring instrument.

[0055] In step 204, which involves performing thermal analysis, the sample carrier 10 is subjected to a temperature load within the test chamber 18. This temperature load can be performed using a specified temperature profile or a constant temperature. In this case, the temperature range may be -200°C to +250°C, preferably -80°C to +200°C. With respect to materials, the system 20, sample carrier 10, and single sensor 12 or sensor plate 13 are configured such that the upper and lower temperature limits do not affect the measurement performance or durability of each element. During the temperature load, the single sensor 12 detects the amount of heat released or absorbed by the single sample during thermal analysis and transmits the sensor value to the evaluation unit 16. This method envisions a step 205 in which the measuring instrument simultaneously acquires measurements of a single sample or a group of single samples. This means that multiple single samples can be processed in a single measurement cycle, thus providing the potential to significantly improve sample throughput. For example, when a microtiter plate 14 equipped with 96 sample containers is used, 96 single samples can be analyzed simultaneously, and corresponding measurement data can be output. This results in a significant improvement in processing power and time during analysis compared to conventional methods of measuring samples individually. The configuration of the system 20 ensures that a reliable single value is obtained for each single sample and made available for analysis. Simultaneous analysis also allows for the evaluation of measurement data for a single sample or a group of samples, either individually or as a group. Step 206, in which the measured values ​​are transmitted to an evaluation unit 16 that communicates with the measuring instrument, is performed via an interface 21 provided in the system 20. This transmission can be done via wired or wireless connection, such as Bluetooth or WLAN. The acquired measured values ​​are transferred to a downstream evaluation entity, such as a computer with corresponding software, where they are further analyzed. Visual display of the acquired and / or evaluated measured values ​​can also be simultaneously displayed on a display 22 provided in the system 20, and operating parameters of the system 20, such as the temperature gradient in the test chamber 18, can also be displayed via the display 22 in addition to the measurement results.For simultaneous evaluation of measured values ​​and estimation of the characteristic data structure of a single sample or a group of single samples based on the measured values, the raw data provided from the single sensor 12 is processed and provided for detailed evaluation of the analysis performed. In this case, the detailed evaluation can be performed by software assistance or manually in the evaluation unit 16 or a downstream evaluation entity.

[0056] In the detailed description above, different features are combined into one or more examples to enhance the rigor of the description. However, it is clear that the description above is merely illustrative and not limiting. It is intended to encompass all alternatives, modifications, and equivalents of the different features and exemplary embodiments. Those skilled in the art will be able to immediately and directly understand many other examples based on their technical knowledge, considering the description above.

[0057] The exemplary embodiments have been selected and described in a manner that best illustrates the underlying principles of the invention and their practical applicability. This will enable experts to best modify and utilize the invention and its different exemplary embodiments for their intended use. The terms “includes” and “have” are used neutrally with respect to the corresponding term “equipped with” in the claims and specification. The terms “a,” “an,” and “one” do not preclude any multiple features and components described herein. [Explanation of Symbols]

[0058] 10 Sample carriers 11. Sample container 12 Single Sensors 13 Sensor Plate 14 Micro Titer Plates 15 Bottom 16 evaluation units 17 Housing 18 Test Chamber 19 Heating or cooling unit 20 Systems 21 Interface 22 displays 23 Observation window 24 Microscopes 25 Camera equipment 26 Lighting Units 201 Steps to introduce a single sample 202 Steps to introduce the sample carrier 203 Steps to connect a single sensor 204 Steps to perform thermal analysis 205 Steps to simultaneously acquire measurement values 206 Steps to send measurement values 207 Steps for simultaneously evaluating measured values G surface area

Claims

1. A system (20) for simultaneous thermal analysis of multiple single samples, particularly biological materials, using differential scanning calorimetry (DSC), - A sample carrier (10) having a plurality of sample containers (11), wherein each sample container (11) is assigned a single sensor (12) for measuring the amount of heat released or absorbed from the single sample during thermal analysis, and the at least one sample carrier (10), - A heating and / or cooling unit (19) having a receptacle for at least one sample carrier (10) and for simultaneously applying temperature to the single sample contained in the sample container (11), - A measuring instrument connected to the single sensor (12) and configured to simultaneously acquire measured values ​​of the amount of heat emitted or absorbed by the single sample during thermal analysis, A system equipped with these features.

2. The system (20) according to claim 1, wherein the receptacle is located in a test chamber (18), and the environmental conditions within the test chamber (18) are defined or configured to be variably adjustable.

3. The system (20) according to claim 2, wherein the specified or variably adjustable environmental conditions within the test chamber (18) are selected from temperature, pressure, relative humidity, (inert) gas atmosphere, and combinations thereof.

4. A system (20) according to any one of claims 1 to 3, further comprising an evaluation unit (16) configured to receive the measured values ​​from the measuring instrument, analyze the measured values, and evaluate the characteristic data structure of each single sample based on the measured values.

5. A system (20) according to any one of claims 1 to 4, further comprising a display (22) configured to visualize measured values ​​and / or data structures.

6. A system (20) according to any one of claims 1 to 5, wherein the single sensor (12) is integrated into a sensor plate (13), the number of single sensors (12) on the sensor plate (13) corresponds to the number of sample containers (11) on the sample carrier (10), and the single sensor (12) is positioned on the sensor plate (13) at a position corresponding to the position of the sample container (11).

7. The system (20) according to claim 6, wherein the sensor plate (13) is provided as a separate element that can be connected to the sample carrier (10) in a shape-tight or friction-engagement manner.

8. The system (20) according to claim 6, wherein the sensor plate (13) is configured as an element placed on a receptacle.

9. A system (20) according to any one of claims 1 to 5, wherein each sample container (11) is provided with a single sensor (12) integrated within it, or a single sensor that can be connected to each sample container (11) in a shape-fitting or friction-engagement manner.

10. A system (20) according to any one of claims 1 to 9, wherein the surface area of ​​the single sensor (12) substantially corresponds to the surface area (G) of the sample container (11).

11. A system (20) according to any one of claims 1 to 10, wherein the evaluation unit (16) further comprises an interface (21) configured to establish a communication connection between the evaluation unit (16) and an external communication participant.

12. A system (20) according to claim 11, wherein the external communication participant is configured as a data processing device and is communicated with the evaluation unit (16) via the interface (21).

13. A system (20) according to at least one of claims 1 to 12, wherein the system (20) further comprises an illumination unit (26), the illumination unit (26) being selected from a UV light illumination unit, an illumination unit designed to emit visible light, an illumination unit designed to emit infrared light, an illumination unit designed to emit polarized light, and an illumination unit designed to emit fluorescence, particularly blue, green, or red fluorescence.

14. A system (20) according to at least one of claims 1 to 13, wherein the heating and / or cooling unit (19), the receptacle for at least one sample carrier, the measuring instrument, the evaluation unit (16), the test chamber (18), the illumination unit (26), and / or the display (22) are at least partially enclosed by a housing (17), in particular a common housing (17).

15. A system (20) according to any one of claims 1 to 14, wherein an interface (21) and / or observation window (23) for arranging an optical evaluation device, in particular a camera device (25), a microscope device, a fluorescence microscope, or a Raman device.

16. A system (20) according to claim 14 or 15, wherein the interface (21) and / or the observation window (23) are provided to be integrated with the housing (17) and / or the test chamber (18).

17. A system (20) according to any one of claims 1 to 16, wherein the sample carrier (10) is configured as a microtiter plate (14) having a standardized configuration, and the receptacle is configured as an insert tray for the microtiter plate (14).

18. A sample carrier (10) for use in a system (20) according to any one of claims 1 to 17, wherein the sample carrier (10) comprises a plurality of sample containers (11) arranged in a predetermined grid for each single sample.

19. A sample carrier (10) according to claim 18, wherein the sample carrier (10) comprises 6 to 1536 sample containers (11) and is configured as a standardized microtiter plate (14) made of a heat-resistant material, particularly a plastic material.

20. A sample carrier (10) according to claim 19, wherein the plastic material has heat resistance in a temperature range of -200°C to +250°C, preferably -80°C to +200°C.

21. A sample carrier (10) according to any one of claims 18 to 20, wherein a single sensor (12) for measuring the amount of heat released or absorbed from a single sample during thermal analysis is assigned to each sample container (11).

22. A sample carrier (10) according to claim 21, wherein the single sensor (12) is integrated within the sample container (11) or is connectable to the sample container (11) in a shape-fitting or friction-engagement manner.

23. A sample carrier (10) according to any one of claims 18 to 21, wherein a number of single sensors (12) corresponding to the number of sample containers (11) are integrated into a sensor plate (13) that can be connected to the sample carrier (10) in a shape-fitting or friction-engagement manner, and the single sensors (12) are positioned on the sensor plate (13) at positions corresponding to the positions of the sample containers (11).

24. In particular, a method for simultaneously analyzing multiple single samples or groups of single samples of a biological material, in the system described in any one of claims 1 to 17, by differential scanning calorimetry (DSC), - A sample carrier (10) having a single sensor (12) assigned to each sample container (11), particularly a sample carrier (10) according to any one of claims 18 to 23, a step (201) of introducing a single sample into the sample container (11), - The step (202) of introducing the sample carrier (10) into a heating and / or cooling unit, - The single sensor (12) is connected to the measuring instrument (203), - The step (204) of performing the thermal analysis while simultaneously measuring the amount of heat emitted or absorbed by the single sample during the thermal analysis using the single sensor 12, - A step (205) of simultaneously acquiring measurement values ​​of the single sample or group of single samples using the measuring instrument, - A step (206) of transmitting the measured value to an evaluation unit (16) that communicates with the measuring instrument, - The evaluation unit (16) simultaneously evaluates the measured values ​​and estimates the characteristic data structure of the single sample or group of single samples based on the measured values ​​(207), Methods that include...

25. A method according to claim 24, wherein the analysis is carried out under specified or variably adaptable environmental conditions, the specified or variably adaptable environmental conditions being selected from temperature, pressure, relative humidity, (inert) gas atmosphere, and combinations thereof.

26. A method according to claim 24 or 25, further comprising visually analyzing the single sample or group of single samples using an optical evaluation device, in particular a camera device (25), a microscope device, a fluorescence microscope, or a Raman device.

27. A method according to any one of claims 24 to 26, wherein the analysis is performed at a specified temperature profile.

28. A method according to any one of claims 24 to 27, wherein the simultaneous evaluation step (207) is performed automatically or manually in the evaluation unit (16).

29. A method according to at least one of claims 24 to 26, further comprising visualizing the data structure in particular on a display (22).

30. A system (20) according to at least one of claims 1 to 17, and / or use of a sample carrier according to any one of claims 18 to 23, for simultaneous thermal and / or visual analysis of a single biological sample, particularly by differential scanning calorimetry (DSC).

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