System for simultaneous thermal analysis of plurality of individual samples of material, in particular biological material, by dynamic DSC, sample carrier and method for simultaneous analysis of plurality 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 material, by dynamic differential scanning calorimetry (DSC), comprising: at least one sample carrier having a plurality of sample containers, each sample container being assigned a single sensor, the heat meter is used for measuring heat released or absorbed by a single sample in a thermal analysis process; a heating unit and / or a cooling unit for simultaneously applying a temperature to the individual samples contained in the sample container, the heating unit and / or cooling unit having a receptacle for at least one sample carrier; a measuring device, which is connected to the individual sensor and is designed for this purpose to simultaneously detect a measured value of the heat released or absorbed by the individual sample during the thermal analysis process, the invention also relates to a sample carrier, in particular for use in said system, and to a method for simultaneous analysis of a plurality of individual samples or groups of individual samples by dynamic differential scanning calorimetry (DSC).

Description

Technical Field

[0001] The present invention relates to a system for simultaneously performing thermal analysis of multiple individual samples of a material (especially biological material) by differential scanning calorimetry (DSC), a sample carrier particularly for the system, and a method for simultaneously analyzing multiple individual samples. Background Technology

[0002] Differential scanning calorimetry (DSC) is a thermal analysis method used to measure the amount of heat released or absorbed by a sample during heating, cooling, or isothermal processes. DSC can be used for a variety of analyses, such as melting point and glass transition temperature analysis, crystallinity analysis, chemical reaction kinetics analysis, specific heat capacity analysis, and phase transition analysis. DSC is also used in disease identification and medical research. Typically, the measuring equipment used for DSC analysis only allows for the simultaneous analysis of small numbers of samples or a single sample. Therefore, at high sample volumes and due to the low analytical capacity per unit time, the required waiting time for analysis can be particularly long. Because single-sample measurements are correspondingly time-consuming, analysis cannot be performed at an economical scale. Traditional measuring equipment also requires large sample volumes of 15 µl or more for repeatable measurements. Therefore, the known measuring equipment is not commercially viable.

[0003] The equipment and methods typically used for research purposes are known.

[0004] US 2019 / 0003995 A1 describes a dynamic differential scanning calorimeter for identifying diseases and monitoring treatment efficacy by recognizing thermally stable variants of proteins and / or metabolites in biological samples.

[0005] WO 2017 / 066800 A1 describes a method for characterizing and / or predicting risks associated with biological samples using thermal stability features. Summary of the Invention

[0006] The purpose of this invention is to provide a cheaper, simpler, and faster method for analysis using dynamic differential scanning calorimetry.

[0007] According to the present invention, this objective is achieved by the subject matter of the independent claims.

[0008] According to a first aspect of the invention, a system is provided for simultaneously performing thermal analysis on multiple individual samples of a material (particularly biological material) using dynamic differential scanning calorimetry (DSC). The system comprises: at least one sample carrier having multiple sample containers, wherein a single sensor is assigned to each sample container for measuring the heat released or absorbed by the individual sample during the thermal analysis; a heating unit and / or a cooling unit for simultaneously applying temperature to the individual samples contained within the sample containers, the heating unit and / or cooling unit having a receiving portion for at least one sample carrier; and a measuring device connected to the individual sensor and configured to simultaneously detect measurements of the heat released or absorbed by the individual samples during the thermal analysis.

[0009] According to a second aspect of the invention, a sample carrier is provided, particularly for the aforementioned system, wherein the sample carrier has a plurality of sample containers preferably arranged in a defined grid, each for a single sample.

[0010] According to a third aspect of the invention, a method is provided for the simultaneous analysis of multiple individual samples or groups of individual samples, particularly biological materials, by dynamic differential scanning calorimetry (DSC), especially in the aforementioned system. This method includes the following steps: placing individual samples into sample containers within a sample carrier (particularly a sample carrier as described above), each sample container being equipped with a single sensor; placing the sample carrier into a heating unit and / or a cooling unit; connecting the individual sensors to a measuring device; performing thermal analysis and simultaneously measuring the heat released or absorbed by the individual sample during the thermal analysis using the individual sensors; simultaneously detecting the measurement values ​​of the individual sample or group of individual samples using the measuring device; sending the measurement values ​​to an evaluation unit communicating with the measuring device; and simultaneously evaluating the measurement values, and deriving a characteristic data structure of the individual sample or group of individual samples based on the measurement values ​​using the evaluation unit.

[0011] According to a fourth aspect of the invention, a system according to the invention and / or a sample carrier according to the invention are provided for the use of simultaneously performing thermal and / or visual analysis on a single sample, particularly a biological sample, by differential scanning calorimetry (DSC).

[0012] A fundamental concept of this invention is to enable reproducible measurements with high sample throughput even for small sample volumes, while simultaneously reducing the time costs, particularly for sample preparation and analysis of measurement results. This invention can accelerate product development cycles, especially in biotechnology development, and particularly in medical diagnostics, by shortening the time required to obtain analytical results. Furthermore, this invention allows for the simultaneous analysis of multiple samples under identical analytical conditions, thereby yielding differentiated measurement and analytical results.

[0013] Advantageous implementations and improvements are derived from the dependent claims that reference the independent claim and from the description with reference to the accompanying drawings.

[0014] According to one embodiment of the system, the containment unit is arranged in a test chamber, wherein the environmental conditions within the test chamber are designed to be defined or variable-controlled. Therefore, multiple samples can be analyzed simultaneously within a measurement cycle and under the same environmental or measurement conditions, or under variations in the same environmental conditions, such as during the analysis process. This provides advantages in terms of sample throughput and the repeatability of measurement results, and allows for the simultaneous analysis of multiple similar sample series under the same conditions. In this document, the defined or variable-controlled environmental conditions within the test chamber are particularly selected from: temperature, pressure, relative humidity, (inert) gas atmosphere, and combinations thereof.

[0015] According to an improvement, the system according to the invention further includes an evaluation unit configured to receive, analyze, and estimate characteristic data structures for each individual sample based on the measurements from the measuring device. Therefore, the system allows for the simultaneous derivation of data structures from measurements of individual samples already tested under identical conditions, thus enabling comparison across all parameters. Consequently, the repeatability of a large number of measurements and samples can be achieved and improved.

[0016] According to another improvement, the system is equipped with a display designed to visualize measured values ​​and / or data structures. This significantly simplifies the analysis process and allows for the direct display of detected measured values ​​and / or data structures, enabling system users to monitor analyzed and detected measurements in real time before or after evaluation, and to directly display and compare measured values ​​and analysis results. This also provides advantages in quality control and can help improve the efficiency of system use. The display can also be used to display analytical parameters simultaneously. For example, if the display is designed as a touchscreen, it can be used for both system control and for inputting or selecting analytical parameters or programs.

[0017] According to another embodiment of the system, individual sensors are combined in a sensor plate. The number of individual sensors on the sensor plate corresponds to the number of sample containers in the sample carrier. Here, the individual sensors are arranged such that their positions on the sensor plate correspond to the positions of the sample containers. The use of a sensor plate helps simplify the system and improve the positioning of the sensors relative to the sample or relative to the sample container. The sensors are combined in the sensor plate and fixed at standardized positions defined within the sensor plate. Because the positioning accuracy and position fidelity of the sensors are guaranteed, consistently high-quality measurement results are also ensured.

[0018] In this document, another advantageous embodiment of the system according to the invention specifies that the sensor plate is provided as a separate component, which can be connected to the sample carrier by form-fit or force-fit. Therefore, the sensor plate can be connected to the sample carrier in a simple manner, such as by plugging it into it, locking it to it, or connecting it via clips. This significantly speeds up measurement or measurement preparation procedures, such as sample preparation or sample carrier preparation, and improves positioning and repeatability. Data cables connected to the sensor can also be incorporated into the sensor plate and integrated into the system via connections (e.g., plug-in connections).

[0019] According to another alternative implementation of the system, the sensor plate is designed to be a permanently arranged element within the receiving compartment and retained there. For measurement, the sample carrier is simply placed, inserted, locked, or clipped into the sensor plate, which is fixedly positioned in the receiving compartment. Thus, the sensor plate is permanently retained in the receiving compartment and, consequently, in the system, making sample carrier positioning significantly easier and faster. Since the sensor plate does not directly contact the sample, there is no risk of contamination or cross-contamination within the system. Furthermore, there is no need to clean the sensor plate or perform complex sterilization procedures after measurement, thereby improving the system's user-friendliness and increasing the sample throughput per unit time.

[0020] In another alternative embodiment of the system according to the invention, a single sensor is provided integrated into each sample container or can be connected to each sample container in a shape-fitting or force-fitting manner. This enables individual control of each individual sample container. This embodiment also allows for the evaluation of sample carriers that are only partially filled.

[0021] According to another embodiment, the bottom surface of a single sensor substantially corresponds to the bottom surface of the sample container. This ensures that measurements are detected across the entire bottom surface of the sample container, thereby significantly improving measurement accuracy.

[0022] According to another embodiment, the evaluation unit further includes an interface or communication interface designed to establish a communication connection between the evaluation unit and external communication participants. This enables the evaluation unit to transfer datasets from the system to, in particular, a data storage device (e.g., a cloud or similar device) or a server without itself being communicatively coupled to the server or similar device. In this way, data transmission is more convenient and can be protected during transmission if necessary. Here, the interface can be designed for wired or wireless data transmission. For example, it can be transmitted via Bluetooth, WLAN connections, or other communication standards familiar to those skilled in the art, and is covered in this invention.

[0023] According to an improved version, the system also includes an illumination unit selected from: an ultraviolet 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). Therefore, the system can simultaneously perform spectral analysis on the sample during thermal analysis, expanding the range of measurements and spectral data available through the system. During thermal analysis, internal processes within the sample can also be visually detected or visualized.

[0024] According to another embodiment of the system, the heating unit and / or cooling unit, the housing 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). Thus, the system, or at least its components, are compactly combined into a single unit, and a portable system design is also achieved.

[0025] According to another embodiment of the system, an interface and / or observation window are provided for arranging optical evaluation devices, particularly imaging devices, microscope devices, fluorescence microscopes, or Raman devices. This enables visual inspection of the analytical process and optical analysis of the sample, thereby improving the evaluation of measurement results and expanding the bandwidth of analytical methods that can be performed using the system, especially when used in conjunction with the aforementioned illumination unit and the illumination options provided therefrom.

[0026] According to another embodiment of the system, the interface and / or observation window are integrated into the housing and / or test chamber. The integrated interface allows the system to be easily and quickly connected to third-party devices and optical evaluation equipment, while the observation window enables direct optical observation of the sample and allows for visual evaluation, for example, using a camera or microscope.

[0027] According to another embodiment, the sample carrier is designed as a microtiter plate with a standardized configuration, and the receiving portion is designed as a slot for the microtiter plate. This allows for high sample throughput, while the microtiter plate, depending on its configuration, also allows for the measurement of small volumes, particularly less than 10 µl in a single sample. The slot significantly improves the system's user-friendliness, as the microtiter plate can be repeatedly positioned in the system before each measurement.

[0028] According to an improved design of the sample carrier, which is a standardized microtiter plate made of heat-resistant materials, particularly plastics, it has 6 to 1546 sample containers. This allows for the simultaneous measurement of large numbers of samples with high reproducibility and significantly increases sample throughput. Furthermore, using a standardized microtiter plate (e.g., the so-called 96-well microtiter plate format used in laboratories) allows for the same standardized design of the sensor plate described earlier for connection. This simplifies the precise placement of the measuring sensor relative to the sample containers in the microtiter plate. Since the standardized format of the sample carrier also significantly accelerates automated sample preparation, this results in a corresponding advantage in sample throughput. The standardized microtiter plate can also be placed into a correspondingly matching container in the measurement system, allowing the system to load large numbers of samples quickly and easily. After analysis, the microtiter plate can be discarded or cleaned and reused, making the system immediately available for the next measurement.

[0029] According to another embodiment of the sample carrier, the plastic material has a high-temperature resistance of -200°C to +250°C, preferably within a temperature range of -80°C to +200°C. This allows for measurements to be performed within a high-temperature range without damage to the sample carrier during measurement. Furthermore, measurements can be performed using sample carriers directly from cryogenic storage. This allows for the preparation of large quantities of samples for measurement, stored at extremely low temperatures (e.g., -80°C), and then processed in the system without requiring additional preparation steps prior to the corresponding analysis or measurement. This improves system efficiency and sample throughput.

[0030] According to another embodiment of the sample carrier, a single sensor is assigned to each sample container to measure the heat released or absorbed by a single sample during thermal analysis. Therefore, the system can operate with multiple single sensors performing measurements simultaneously. This explicit allocation of individual sensors to sample containers ensures that only the corresponding single sample is measured by the sensor. The single sensor is sufficiently miniaturized to reliably and repeatably detect the measurements of a single sample in the aforementioned microtiter plate, even with the smallest possible measurement volume.

[0031] According to another embodiment of the sample carrier, individual sensors are integrated into the sample container, or can be connected to the sample container in a form-fit or force-fit manner. In this way, a sample carrier can be provided in which individual sensors are arranged in each or only a single sample container. Thus, a properly prepared sample carrier suitable for measurement in the aforementioned system is provided. This sample carrier can be provided as a consumable or system accessory.

[0032] In an alternative implementation, individual sensors can be connected to corresponding sample containers as needed. This allows the use of standardized sample containers, which can be prepared for measurement by equipping them with individual sensors. The sample containers, such as standardized microtiter plates, can be detached from the individual sensors after use, discarded, or cleaned and reused. This increases system flexibility and measurement efficiency, thereby increasing sample throughput.

[0033] According to another embodiment, individual sensors are combined in a sensor plate, and the number of individual sensors on the sensor plate corresponds to the number of sample containers in the sample carrier. Here, the individual sensors are arranged in the sensor plate at positions corresponding to the sample containers. The use of the sensor plate significantly simplifies system operation because the bottom surface 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, allowing connection to the sample carrier before measurement. This connection can be formed by, for example, plugging, locking, clamping, or any other suitable method, creating a form-fit or force-fit connection. The connection between the sensor plate and the sample carrier has high positioning accuracy, ensuring that the sample held in the sample container can be measured repeatedly and with high precision. After analysis, the sensor plate can be easily detached from the sample carrier and prepared for the next measurement. Thus, a modular system is provided that can be used efficiently and handle high sample volumes, thereby saving time and costs.

[0034] According to one embodiment of the method, analysis is performed under defined or variable-controlled environmental conditions. Here, environmental conditions are selected from temperature, pressure, relative humidity, (inert) gas atmosphere, and combinations thereof. The method specifies that the performance of a sample under different environmental condition parameters can be measured by maintaining constant environmental conditions simultaneously during the measurement process, or by generating appropriate curves for environmental conditions (e.g., variable temperature, variable pressure, humidity changes, or gas atmosphere) within the system. Various environmental conditions within the system are monitored by suitable sensors, which are arranged, for example, in a test chamber or a housing as described above. Environmental conditions can also be displayed on the aforementioned display or integrated into a dataset to ensure complete traceability and / or repeatability of the measurements.

[0035] According to an improvement to this method, the method further includes visual analysis of individual samples or groups of samples using optical evaluation devices, particularly imaging devices, microscopic devices, fluorescence microscopes, or Raman spectrometers. In addition to or instead of measurements acquired via the aforementioned sensors, samples can be visually evaluated during the analysis process to draw additional conclusions about sample composition or the properties of the sampled materials during thermal analysis. Visual inspection of individual samples or groups of samples is preferably performed via the aforementioned interface or a corresponding observation window in the test chamber or system housing. Visual measurements can also be automatically acquired within the system, and the corresponding dataset is output through the system in combination with the dataset acquired via sensors. The combination of acquired sensor values ​​with additional or alternatively acquired visual parameters of the samples increases the system's flexibility and expands its application range, thus enabling the system to be easily adjusted or prepared for various measurement tasks.

[0036] An improved version of this method specifies that the analysis is performed within a defined temperature profile. This operation can be performed simply and repeatedly using the aforementioned scheme of varying environmental conditions, and can be controlled automatically or manually.

[0037] In a preferred embodiment of the method according to the invention, the simultaneous evaluation of individual samples in the evaluation unit can be performed automatically or manually. By simultaneously performing thermal analysis on a large number of individual samples in the system according to the invention, the sample throughput and system efficiency can be significantly increased. Therefore, a large dataset can be provided, from which conclusions about sample performance or composition can be directly drawn in the automatic evaluation. Thus, different samples can be compared during measurement or analysis runs. A scheme for manual evaluation allows the user to adjust parameters during or for subsequent analysis processes. Corresponding software is provided in the system for recording and simultaneously evaluating all measurements performed in parallel. This software can be connected to an integrated database to achieve fully automated evaluation. Manual evaluation can also be performed in parallel or as an alternative. Optical analysis can be performed on each sample additionally or alternatively during the measurement process. The corresponding measurements can be detected automatically or manually and preferably evaluated with software support.

[0038] In an improved version, the method further includes a step of visualizing the data structure, particularly on a display. This allows for real-time tracking and analysis, where detected measurements are additionally forwarded to subsequent evaluation instances via the aforementioned interface. Furthermore, visualization of the data structure on the display enables rapid identification of measurement errors or malfunctions in the system.

[0039] The above-described embodiments and improvements can be combined arbitrarily, as long as they are meaningful. Other possible embodiments, improvements, and implementations of the present invention include combinations of features not explicitly mentioned above or described in the embodiments below. In particular, those skilled in the art can add various aspects as improvements or additions to the corresponding basic forms of the present invention. Attached Figure Description

[0040] The present invention will now be described in detail with reference to the accompanying drawings and embodiments. The drawings show:

[0041] Figure 1 A schematic top view of a sample carrier according to an embodiment of the present invention is shown;

[0042] Figure 2 A schematic side view of another embodiment of a sample carrier according to another embodiment of the present invention is shown;

[0043] Figure 3 A schematic perspective view of a system according to an embodiment of the present invention is shown;

[0044] Figure 4 A flowchart of an analytical method according to an embodiment of the present invention is shown, particularly a flowchart of a method for analyzing biomaterials by dynamic differential calorimetry (DSC).

[0045] In the accompanying drawings, unless otherwise specified, the same reference numerals are used for identical, functional, and operational elements, features, and components.

[0046] While specific embodiments and improvements have been presented and described herein, those skilled in the art will understand that various alternatives and / or similar embodiments can be used to replace the specific embodiments shown and described without departing from the scope of the invention. This application is generally intended to cover all variations or modifications of the specific embodiments described herein.

[0047] The accompanying drawings are intended to aid in further understanding of embodiments of the invention and, in conjunction with the specification, to explain the principles and concepts of the invention. Other embodiments and many of the aforementioned advantages are derived through reference to the drawings. The drawings should be understood as schematic diagrams only, and the elements in the drawings are not necessarily drawn to scale. Directional terms such as "up," "down," "left," "right," "above," "below," "horizontal," "vertical," "front," and "back" are used for illustrative purposes only and do not limit the general applicability to the specific designs shown in the figures.

[0048] The dashed lines in the diagram indicate that the connections between the components do not necessarily require physical contact; they can also be wirelessly coupled. Detailed Implementation

[0049] Figure 1 A sample carrier 10 according to an embodiment of the present invention is schematically shown in a top view. The sample carrier 10 shown here is a microtiter plate 14 having a total of 56 individual sample containers 11 arranged in a standardized grid within the microtiter plate 14. Of course, the sample carrier 10 is not limited to the embodiment and configuration shown here. Similarly, a microtiter plate 14 with fewer or more sample containers 11 can also be used in the system 20 of the present invention. The system 20 according to the present invention is designed for a sample carrier 10 with, in particular, 6 to 1536 sample containers 11, and allows for defined and repeatable measurements of each sample. The sample carrier 10 according to the present invention allows for the measurement of small-volume samples, i.e., samples with a volume of 10 µl or less.

[0050] Therefore, the standardized microtiter plate 14 available in a laboratory environment can be used in the system 20 according to the invention. Figure 1 In this embodiment, the sample carrier 10 has a single sensor 12 integrated into each sample container 11. The single sensor 12 measures the heat released or absorbed by a single sample during thermal analysis using differential scanning calorimetry (DSC). Figure 1 The illustrated embodiment shows an integrated sample carrier 10, where a single sensor 12 is securely connected to the sample carrier 10 or sample container 11, and the single sensor 12 is integrated into the sample container 11. In an alternative embodiment not shown, the single sensor 12 may also be detachably and individually connected to the corresponding sample container 11 in the form of a sensor plate having the same bottom surface as the sample container 11, for example, by plugging it into it, clamping it to it, or otherwise connecting it to it. Therefore, the sample carrier 10 can be customized using a single sensor 12, i.e., configured on demand.

[0051] Figure 2 A side view schematically illustrates another embodiment of the sample carrier 10 according to another embodiment of the present invention. Already related to... Figure 1The individual sensors 12 described herein are combined here in a sensor plate 13 disposed below the microtiter plate 14. The sensor plate 13 has a number of individual sensors 12 corresponding to the number of sample containers 11 in the sample carrier 10, these individual sensors being securely coupled into a single unit, namely the sensor plate 13. Prior to thermal analysis using dynamic differential calorimetry (DSC), the sensor plate 13 is connected to the sample carrier 10 (in this embodiment, the microtiter plate 14) and held in that position during measurement. The connection to the sample carrier 10 is detachable; that is, the sensor plate 13 is inserted into, locked to, or clipped onto the sample carrier 10. The sensor plate 13 is configured here to allow for precise positioning on the microtiter plate 14. After the sensor plate 13 is positioned on the sample carrier 10, the individual sensors 12 are located below each sample container 11 and cover its entire bottom surface G. This allows for a comprehensive measurement of the entire sample container 11. After analysis, the sensor plate 13 is removed from the sample carrier 10 and can be immediately reattached to another sample carrier 10 determined for subsequent measurements. Since the sensor plate 13 does not contact the sample to be measured, but rather measures through the sample carrier 10 or its bottom 15, there is no risk of contamination of the sensor plate 13, thus eliminating the need for cleaning before subsequent measurements. Nevertheless, the sensor plate 13 can still be made of a correspondingly sterilizable material, in which individual sensors 12 are embedded in the sensor plate 13 in a liquid-tight and gas-tight manner. The sensor plate 13 can be adapted to various configurations of the sample carrier 10 in terms of geometry and the number of individual sensors 12 in the sensor plate 13, so as to always provide a suitable sensor plate 13 for the corresponding sample carrier 10. The sample carrier 10 can be, for example, a microtiter plate 14 suitable for use in a laboratory environment, having 6 to 1536 sample containers 11, i.e., so-called wells. The individual sensors 12 here are matched to the existing bottom surface of the respective sample containers 11. The individual sensor 12 is miniaturized enough to ensure that its surface covers the sample container 11 or the bottom 15 of the sample container 11 without being affected by adjacent sample containers 11 during measurement. The corresponding data lines (not shown) of the individual sensor 12 are also integrated into the sensor plate 13, giving the sensor plate 13 a single interface for connection to the system 20, allowing the system 20 to output the detected measurement value and provide it to the evaluation unit 16. For thermal analysis, the sensor plate 13 is fixed to the sample carrier 10, and then 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 can be mounted in the analysis system, and the sample carrier 10, containing only the single sample to be measured and housed therein, can be inserted into the housing here and connected to the sensor plate 13 simultaneously or subsequently.

[0052] Figure 3A system 20 according to an embodiment of the present invention is schematically shown in a perspective view. The system 20 according to the invention includes a housing 17 containing a test chamber 18, in which a sample carrier 10 containing a sample to be analyzed is placed. Corresponding to the test chamber 18, the housing 17 has a heating or cooling unit 19, through which the sample can be heated according to a defined temperature profile. The test chamber 18 has a receiving portion (not shown here) for placing the sample carrier 10. Figure 3 In this embodiment, the sample carrier 10 is a correspondingly configured microtiter plate 14 with a plurality of sample containers 11 securely assembled within the microtiter plate 14. These sample containers 11 are filled with the corresponding sample before thermal analysis, which is then performed simultaneously in the system according to the invention. For this purpose, a sensor plate 13 is arranged below the sample carrier 10, such as in combination with… Figure 2 The individual sensor 12 is assigned to a corresponding sample and detects temperature changes in the sample during thermal analysis. Sensor data is evaluated directly within system 20. For this purpose, system 20 includes an evaluation unit 16 to which sensor data is transmitted and evaluated. Simultaneously, analytical data can be output to a subsequent evaluation instance (not shown) via an interface 21 present in system 20 and arranged in housing 17. This interface can be, for example, a computer unit with corresponding evaluation software. The detected values ​​can also be directly evaluated using the evaluation unit 16 through the implementation of system 20 shown in this embodiment. The evaluation results are then displayed visually on a display 22 arranged in housing 17. Display 22 also displays operating parameters of system 20, such as temperature changes, temperature gradients, or other environmental conditions set in test chamber 18, which are parameters of the corresponding analytical method. Display 22 can also be designed as a touchscreen and used as an input device for control system 20. Parameters can be changed, input, or measurements can be started or stopped via display 22. In this embodiment, the display 22 is securely connected to the housing 17. Of course, a separate display 22 can also be provided, connected to the system 20 via the aforementioned interface 21. The display 22 can also be integrated into the system 20 or designed as part of a computer unit that can be connected to the system 20.

[0053] In this embodiment, the housing 17 also has an observation window 23 through which the sample can be visually inspected. Visual inspection can be performed using a microscope 24 or a camera device 25, a fluorescence microscope, or a Raman spectroscopy device. These devices are connected to the system 20, i.e., arranged within, on, or inside the housing 17. According to... Figure 3In one embodiment, the test chamber 18 itself contains an illumination unit 26, which may be designed as an ultraviolet illumination unit, an illumination unit emitting visible light, an illumination unit emitting infrared light, an illumination unit emitting polarized light, or an illumination unit emitting fluorescence (especially blue, green, or red fluorescence). This illumination unit 26 supports visual inspection of the sample during thermal analysis.

[0054] Figure 4 A flowchart is shown of a method for simultaneously analyzing multiple individual samples or groups of individual samples, particularly biological materials, using dynamic differential scanning calorimetry (DSC), particularly in the system according to the invention as described above. The method includes the following steps: introducing an individual sample into a sample container 11 within a sample carrier 10 (particularly the sample carrier 10 described above), the sample carrier 10 having a single sensor 12 assigned to the corresponding sample container 11; introducing the sample carrier 10 into a heating unit and / or cooling unit 19; connecting the single sensor 12 to a measuring device 203; performing thermal analysis 204 and simultaneously measuring the heat released or absorbed by the single sensor 12 during the thermal analysis; simultaneously detecting the measurement values ​​of the individual sample or group of individual samples by the measuring device 205; sending the measurement values ​​206 to an evaluation unit 16 communicating with the measuring device; and simultaneously evaluating 207 the measurement values, and deriving a characteristic data structure of the individual sample or group of individual samples based on the measurement values ​​using the evaluation unit 16. In the method according to the invention, biological materials, such as blood, urine, sweat, or skin tissue of animal or human origin, can be analyzed by dynamic differential scanning calorimetry (DSC). Furthermore, other materials can also be analyzed in this method. Therefore, the method is not limited to the use of biological materials.

[0055] To introduce a single sample, it is placed or filled into sample container 11. Sample container 11 is part of a sample carrier 10 containing multiple sample containers 11. The sample carrier 10 may be, for example, a microtiter plate 14 with a standardized configuration and surface area, which can be filled or inserted with a sample, for example, by a pipette. The sample is applied to a single sensor 12 assigned to the corresponding sample container 11. However, the single sensor does not directly contact the sample but is separated from it by the sample carrier 10. Nevertheless, the sample carrier 10 is configured such that a non-destructive measurement can be performed by a single sensor 12.

[0056] To introduce the sample carrier 10 to the heating unit and / or cooling unit 19 at 202, the existing test chamber 18 is opened, and the sample carrier 10 is placed into the receiving portion provided in the test chamber 18. After placement, individual sensors 12 are connected to the measuring device at 203. Here, individual sensors 12 can be connected to the measuring device separately, for example via a plug-in connection. Alternatively, the respective individual sensors 12 can be combined in a single plug-in connection and then connected to the corresponding interface within the test chamber 18. In an alternative embodiment, the individual sensors 12 are combined in a sensor plate 13, which also has wiring for the respective combination of individual sensors 12 and is equipped with a plug-in connector for connection to the measuring device.

[0057] For thermal analysis 204, a temperature is applied to the sample carrier 10 in the test chamber 18. This can be done by applying a defined temperature profile or 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, sample carrier 10, and individual sensors 12 or sensor plates 13 are implemented in terms of materials such that their respective upper and lower temperature limits do not impair the measurement performance or durability of the components. During temperature application, the heat released or absorbed by a single sample during thermal analysis is detected by the individual sensor 12 and transmitted as a sensor value to the evaluation unit 16. In this method, the measurement values ​​of 205 individual samples or groups of individual samples are simultaneously detected by the measuring device. That is, a large number of individual samples can be processed in a single measurement cycle, thus significantly improving sample throughput. When using a microtiter plate 14 with, for example, 96 sample containers, 96 individual samples can be analyzed simultaneously, and the corresponding measurement data can be output accordingly. Compared to traditional methods of measuring individual samples, this method achieves significant capacity improvements and time savings during the analysis process. The configuration of system 20 ensures the reliable individual values ​​of each single sample are detected and used for analysis. Simultaneously, the analysis also allows for individual or grouped evaluation of measurement data for single samples or groups of samples. Measurement values ​​are transmitted 206 to evaluation unit 16 via interface 21 provided in system 20, which communicates with the measuring device. This transmission can be wired or wireless, such as via Bluetooth or WLAN. The detected measurements are then forwarded to subsequent evaluation instances, such as computers equipped with appropriate software, where further analysis is performed. Simultaneously, the detected and / or evaluated measurements can also be visually displayed on display 22 provided in system 20, which, in addition to the measurement results, can also display operating parameters of system 20, such as the temperature gradient in test chamber 18. During the simultaneous evaluation 207 of the measurements and the derivation of characteristic data structures for individual samples or groups of samples based on the measurements, the raw data provided by the individual sensor 12 is processed and can be used for detailed evaluation of the performed analysis. Detailed evaluation can be performed here in evaluation unit 16 or in subsequent evaluation examples, either in a software-supported manner or manually.

[0058] In the foregoing detailed description, various features have been combined in one or more examples to enhance the rigor of the description. However, it should be clearly stated that the above description is illustrative rather than limiting. It is intended to cover all alternatives, modifications, and equivalents to the various features and embodiments. Given the foregoing description, those skilled in the art will readily understand many other examples based on their technical knowledge.

[0059] These embodiments were chosen and described in order to present, as best as possible, the basic principles of the invention and its potential applications in practice. This will enable those skilled in the art to modify and utilize the invention and its various embodiments in the best manner according to their intended use. In the claims and description, the terms "comprising" and "having" are used as neutral linguistic terms corresponding to the corresponding term "comprising". Furthermore, the use of the term "a" is not intended to exclude multiple such described features and components. List of reference numerals

[0060] 10 sample carriers 11 Sample Containers 12 individual sensors 13 sensor boards 14 Microtiter Plates 15 bottom 16 assessment units 17 housing 18 Test Rooms 19 heating or cooling units 20 system 21 interface 22 monitors 23 Observation Window 24 microscopes 25 camera devices 26 lighting units 201 Introducing a single sample 202 Introduction of Sample Vector 203 connects a single sensor 204 thermal analysis 205 Simultaneous Detection Measurement Values 206 Send Measurement Values 207 Simultaneous Evaluation Measurements G bottom surface

Claims

1. A system (20) for simultaneously performing thermal analysis on multiple individual samples of a material by dynamic differential scanning calorimetry (DSC), said material being, in particular, a biological material, said system (20) comprising: - At least one sample carrier (10) having multiple sample containers (11), wherein a single sensor (12) is assigned to each of the sample containers (11) for measuring the heat released or absorbed by a single sample during thermal analysis; - A heating unit and / or a cooling unit (19) for simultaneously applying temperature to a single sample contained in the sample container (11), the heating unit and / or cooling unit (19) having a receiving portion for at least one of the sample carriers (10); - A measuring device connected to the single sensor (12) and designed to simultaneously detect the measured value of the heat released or absorbed by the single sample during thermal analysis.

2. The system (20) according to claim 1, characterized in that, The housing is arranged in a test chamber (18), and the environmental conditions within the test chamber (18) are designed to be limited or variable controllable.

3. The system (20) according to claim 2, characterized in that, The defined or variable controlled environmental conditions within the test chamber (18) are selected from: temperature, pressure, relative humidity, (inert) gas atmosphere, and combinations thereof.

4. The system (20) according to any one of the preceding claims, characterized in that, An evaluation unit (16) is also provided, which is designed to receive the measurement values ​​from the measuring device, analyze the measurement values, and estimate the characteristic data structure for each individual sample based on the measurement values.

5. The system (20) according to any one of the preceding claims, characterized in that, It also includes a display (22) which is designed to visualize measurements and / or data structures.

6. The system (20) according to any one of the preceding claims, characterized in that, The individual sensors (12) are combined in a sensor plate (13), and the number of individual sensors (12) in the sensor plate (13) corresponds to the number of sample containers (11) in the sample carrier (10), wherein the individual sensors (12) are arranged such that their positions in the sensor plate (13) correspond to the positions of the sample containers (11).

7. The system (20) according to claim 6, characterized in that, The sensor plate (13) is provided as a separate component, which can be connected to the sample carrier (10) by means of shape fit or force fit.

8. The system (20) according to claim 6, characterized in that, The sensor plate (13) is designed to be arranged as an element in the housing.

9. The system (20) according to any one of claims 1 to 5, characterized in that, Each sample container (11) is equipped with a single sensor (12) that is integrated into it or can be connected to each sample container (11) in a shape-fitting or force-fitting manner.

10. The system (20) according to any one of the preceding claims, characterized in that, The bottom surface of the individual sensor (12) is substantially opposite to the bottom surface (G) of the sample container (11).

11. The system (20) according to any one of the preceding claims, characterized in that, The evaluation unit (16) also includes an interface (21) designed to establish a communication connection between the evaluation unit (16) and external communication participants.

12. The system (20) according to claim 11, characterized in that, The external communication participant is designed as a data processing device and is communicatively coupled to the evaluation unit (16) via the interface (21).

13. The system (20) according to any one of claims 1 to 12, characterized in that, It also includes an illumination unit (26), wherein the illumination unit (26) is selected from: an ultraviolet 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, wherein the fluorescence is particularly blue, green, or red fluorescence.

14. The system (20) according to any one of claims 1 to 13, characterized in that, The heating unit and / or cooling unit (19), the housing for 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), which is in particular a common housing (17).

15. The system (20) according to any one of the preceding claims, characterized in that, An interface (21) and / or an observation window (23) are provided for arranging optical evaluation devices, particularly a camera device (25), a microscope device, a fluorescence microscope or a Raman device.

16. The system (20) according to claim 14 or 15, characterized in that, The interface (21) and / or the observation window (23) are configured to be integrated into the housing (17) and / or the test chamber (18).

17. The system (20) according to any one of the preceding claims, characterized in that, The sample carrier (10) is designed as a microtiter plate (14) with a standardized configuration, and the receiving portion is designed as a slot for the microtiter plate (14).

18. A sample carrier (10), particularly for use in the system (20) according to any one of the preceding claims, characterized in that, The sample carrier (10) has a plurality of sample containers (11) arranged in a defined grid, each of the plurality of sample containers (11) being used for a single sample.

19. The sample carrier (10) according to claim 18, characterized in that, The sample carrier (10) is designed as a standardized microtiter plate (14) made of a high-temperature resistant material, the microtiter plate (14) having 6 to 1546 sample containers (11), wherein the high-temperature resistant material is in particular a plastic material.

20. The sample carrier (10) according to claim 19, characterized in that, The plastic material has high temperature resistance in the temperature range of -200°C to +250°C, preferably in the temperature range of -80°C to +200°C.

21. The sample carrier (10) according to any one of claims 18 to 20, characterized in that, Each sample container (11) is assigned a single sensor (12) for measuring the heat released or absorbed by the single sample during thermal analysis.

22. The sample carrier (10) according to claim 21, characterized in that, The single sensor (12) is integrated into the sample container (11) or can be connected to the sample container (11) in a shape-fitting or force-fitting manner.

23. The sample carrier (10) according to any one of claims 18 to 21, characterized in that, A number of individual sensors (12) corresponding to the number of sample containers (11) are combined in a sensor plate (13), which can be connected to the sample carrier (10) in a form-fit or force-fit manner, and the individual sensors (12) are arranged in the sensor plate (13) at positions corresponding to the positions of the sample containers (11).

24. A method for simultaneously analyzing multiple individual samples or a single sample group by dynamic differential scanning calorimetry (DSC), wherein, The method is carried out, particularly in a system according to any one of claims 1 to 17, wherein a plurality of the individual samples or groups of individual samples are, in particular, biological materials, and the method comprises: - The single sample is introduced (201) into a sample container (11) in a sample carrier (10), the sample carrier (10) being particularly the sample carrier (10) according to any one of claims 18 to 23, with a single sensor (12) assigned to each sample container (11). - Introduce the sample carrier (10) into the (202) heating unit and / or cooling unit; - Connect the single sensor (12) to the measuring device (203); - Perform (204) thermal analysis and simultaneously measure the heat released or absorbed by the single sample during the thermal analysis process using the single sensor (12); - The measurement values ​​of a single sample or a group of single samples are simultaneously detected by a measuring device; - The measured value is sent (206) to the evaluation unit (16) communicating with the measuring device; and - Simultaneously evaluate (207) the measured value, and based on the measured value, derive the characteristic data structure of the individual sample or group of individual samples using the evaluation unit (16).

25. The method according to claim 24, characterized in that, The analysis is performed under defined or variable controlled environmental conditions, wherein the defined or variable controlled environmental conditions are selected from: temperature, pressure, relative humidity, (inert) gas environment, and combinations thereof.

26. The method according to claim 24 or 25 further comprises visual analysis of a single sample or a group of single samples using an optical evaluation device, particularly a camera device (25), a microscope device, a fluorescence microscope, or a Raman device.

27. The method according to any one of claims 24 to 26, characterized in that, The analysis was performed using a defined temperature profile.

28. The method according to any one of claims 24 to 27, characterized in that, Simultaneous evaluation (207) is performed automatically or manually in the evaluation unit (16).

29. The method according to at least one of claims 24 to 26, characterized in that, It also includes visualizing data structures, especially on a display (22).

30. The use of the system (20) according to at least one of claims 1 to 17 and / or the sample carrier (10) according to any one of claims 18 to 23 for simultaneous thermal and / or visual analysis of a single sample, especially a biological sample, by differential scanning calorimetry (DSC).

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