Mixed calorimeter cell

CN117761115BActive Publication Date: 2026-09-01WATERS TECHNOLOGY CORP
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Patent Information

Application Number
CN202311843423.5
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Priority Date
2017-08-31
Filing Date
2018-07-20
Publication Date
2026-09-01
Estimated Expiration
2038-07-20

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Technical Problem

例如,在样品池内加载样品之后,形成池主体的低导热材料可导致较长的平衡时间,以及难以维持用于测量热信号的时间常数

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Abstract

This invention provides a calorimeter cell for a calorimetric system, comprising: a cell body having an internal region for receiving a first substance, the cell body being made of a chemically inert material; and a thermally conductive layer at least partially surrounding the chemically inert cell body. Furthermore, a related calorimeter and method are also provided, the calorimeter comprising: a sample cell; a reference cell; a thermostat in thermal communication with the sample cell and the reference cell; a first conductive line having a first end connected to the thermostat and a second end connected to the sample cell; and a second conductive line having a first end connected to the thermostat and a second end connected to the reference cell.
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Description

[0001] Related applications This patent application is a non-provisional patent application that claims priority to U.S. Provisional Patent Application No. 62 / 553,124, filed August 31, 2018, entitled “CHEMICALLY INERT SAMPLE CELLS FORCALORIMETRY”, which is incorporated herein by reference. Technical Field

[0002] The following relates to calorimetry, and more specifically, to implementation schemes for mixed calorimeter cells used in isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC). Background Technology

[0003] Using low thermal conductivity materials in sample cells for isothermal titration calorimetry and differential scanning applications can degrade calorimeter performance. For example, after loading the sample into the cell, the low thermal conductivity of the material forming the cell body can lead to longer equilibrium times and difficulty in maintaining the time constant used to measure the thermal signal. Materials with appropriately high thermal conductivity may be chemically incompatible with the sample to be tested by the calorimeter.

[0004] Therefore, there is a need for equipment and methods for improving calorimeter cells. Summary of the Invention

[0005] The first aspect relates generally to a calorimeter cell of a calorimetric system, comprising: a cell body having an internal region for receiving a first substance, the cell body comprising a chemically inert material; and a thermally conductive layer that at least partially surrounds the chemically inert cell body, the thermally conductive layer being more thermally conductive than the chemically inert layer.

[0006] The second aspect relates to a calorimeter comprising: a sample cell; a reference cell; a thermostat in thermal communication with the sample cell and the reference cell; a first conductive line having a first end connected to the thermostat and a second end connected to the sample cell; and a second conductive line having a first end connected to the thermostat and a second end connected to the reference cell.

[0007] The third aspect relates to a method comprising: attaching a thermally conductive layer to the outer surface of a cell body of a calorimeter cell, the cell body comprising a chemically inert material; and connecting the thermally conductive layer to a thermostat of the calorimeter using conductive wires.

[0008] The above and other features of the construction and operation will be more readily and fully understood through the following detailed disclosure in conjunction with the accompanying drawings. Attached Figure Description

[0009] Some embodiments will be described in detail with reference to the following figures, wherein similar names denote similar components, wherein: Figure 1 A perspective view of a calorimeter having a sample cell and a reference cell according to an embodiment of the present invention; Figure 2 An embodiment according to the present invention is shown. Figure 1 A sectional view; Figure 3 An embodiment according to the present invention is shown. Figure 2 Detailed view of the surrounding area K; Figure 4 A perspective view of a calorimeter configuration having a conductive line connected to the calorimeter cell according to an embodiment of the present invention is shown. Figure 5 A graph illustrating an embodiment of the invention is shown, demonstrating the advantages of the equilibration time for the added conductive lines in the sample cell; Figure 6 A graph illustrating an embodiment according to the invention is shown, demonstrating the advantages of the thermally conductive layer 70 on the exterior of the sample cell body; and Figure 7 A schematic diagram of a calorimeter with a calorimeter cell according to an embodiment of the present invention is shown. Detailed Implementation

[0010] The following detailed description of embodiments of the apparatus and methods disclosed herein is by way of example and not by reference to the accompanying drawings. While certain embodiments are shown and described in detail, it should be understood that various changes and modifications may be made without departing from the scope of the appended claims. The scope of this disclosure is by no means limited to the number of constituent parts, their materials, their shapes, their relative arrangements, etc., and is disclosed merely as an example of an embodiment of this disclosure.

[0011] As a preface to the detailed embodiments, it should be noted that, unless the context clearly indicates otherwise, the singular forms “a,” “an,” and “described” as used in this specification and the appended claims include plural references.

[0012] Isothermal titration calorimetry is a technique for determining the thermodynamic properties of solutions interacting. For example, exothermic or endothermic reactions generate heat that can be measured using an isothermal titration calorimeter (ITC). Such reactions involve the combination of small molecules with large molecules. A typical ITC includes a reference cell and a sample cell. The reference cell contains a reference liquid, such as water, and the sample cell contains a sample solution containing a first substance. A constant cooling power is applied to the sample cell. A temperature sensing circuit is used to detect the temperature difference between the reference and sample cells. A feedback circuit controls the heater for the sample cell to maintain equal cell temperatures. When a titrant containing a second test substance is injected into the sample cell in a precisely controlled volume, heat is generated or absorbed depending on the type of reaction between the first and second test substances. Therefore, the power supplied to the sample cell by the heater will vary so that the temperatures of the two cells remain equal. This power is monitored over time and results in a series of peaks being observed, each corresponding to the injection of the test solution into the sample cell. Each peak can be integrated over time to generate the total heat generated for the injection. The detected peaks produce information about the thermodynamic parameters of the interaction between the test substances.

[0013] During a single injection, the titrant may not immediately disperse throughout the entire volume of the sample solution, thus the reaction is observed within a finite time corresponding to the width of the observed peak. To mix the solution more quickly, a stirring paddle is rotated within the sample cell. The stirring paddle may include a hollow shaft with stirring blades attached at the end of the shaft within the sample cell. The injection solution can be introduced into the sample cell through the hollow shaft and through bores in the paddle blades. Other injection and stirring mechanisms may include stirring blades separate from the injection needle.

[0014] Furthermore, according to some embodiments, calorimeter cells, such as reference cells and sample cells, can be made of additional low thermal conductivity materials suitable for contact with the sample. The low thermal conductivity material used in the cell construction can be a nickel-based alloy. Some suitable nickel-based alloys are available under the brand HASTELLOY (purchased from Hynes International, Inc., Kokomo, Indiana). These suitable alloys are nickel-based alloys that optionally contain molybdenum and optionally also contain chromium. More generally, the range of HASTELLOY alloys includes varying amounts of nickel (e.g., by weight percentage), and various amounts (e.g., by weight percentage) of molybdenum, chromium, iron, tungsten, manganese, cobalt, aluminum, titanium, silicon, carbon, niobium, vanadium, copper, tantalum, and zirconium. These low thermal conductivity materials can be used in calorimeter cell constructions because they are chemically suitable for inertness, allowing for the testing of multiple sample types and, for example, corrosive chemical cleaning between tests. However, performance problems may arise when such chemically inert materials are used in calorimeter cells due to their poor thermal conductivity. For example, sample cells constructed from nickel-based alloys can withstand degradation of signal, response, and time constant compared to materials with high thermal conductivity.

[0015] Therefore, embodiments of the present invention provide a calorimeter sample cell for use in ITC and DSC, the calorimeter sample cell having: 1) sufficient chemical inertness to allow for a variety of sample types and corrosive chemical cleaning; 2) sufficient thermal conductivity to rapidly conduct heat from the sample through the sample cell and to the thermal sensor, thereby producing, for example, the highest possible sensitivity and response time for the calorimeter; and optionally 3) sufficient thermal connection to the calorimeter thermostat, which facilitates rapid thermal equilibrium of newly loaded samples without negatively affecting sensitivity due to thermal conduction to the thermostat.

[0016] See attached diagram. Figure 1 A perspective view of a calorimeter 300 having a sample cell 100 and a reference cell 200 according to an embodiment of the present invention is shown. The sample cell 100 is a mixing cell comprising a chemically inert, very thin-walled sample cell body 50 having a highly thermally conductive material attached to the exterior of the sample cell body 50. The sample cell body may be made of a nickel-based alloy. In the sample cell 100, the heat conduction path through the thin wall of the chemically inert cell body is sufficiently short, so that heat is conducted through the thin cell wall to the thermally conductive exterior of the cell without significantly increasing the cell response time. The cell body 50 has an internal region 57 for receiving a first substance, and the cell body 50 is made of a thin-walled chemically inert material. A highly thermally conductive layer 70 at least partially surrounds the thin-walled chemically inert cell body 50. Furthermore, the calorimeter 300 may include a constant-cooling thermoelectric device (TED) 10 and a sensor 11 located near the sample cell 100 and the reference cell 200.

[0017] Figure 2It shows Figure 1 The diagram shows a cross-sectional view of the calorimeter 300. The sample cell 100 and the reference cell 200 share a common heat sink. Alternative embodiments of the cell body can be cylindrical, such as for ITC applications, or enclosed capillary cells, such as for DSC applications. The cell body 50 is configured to receive a first substance (e.g., a sample solution) in an internal region 57 of the sample cell 100. During operation of the calorimeter 300, the cell body 50 may also receive a second substance, such as a titrant injected into the cell body 50.

[0018] The cell body 50 of the sample cell 100 is formed of a chemically inert material. The chemically inert material allows for the testing of various sample types and corrosive chemical cleaning between tests. The chemically inert material has a relatively low thermal conductivity. An exemplary embodiment of the cell body 50 is made of a chemically inert, low thermal conductivity material with a thermal conductivity of less than 100 W / mK. Alternatively, the thermal conductivity of the cell body 50 is 1 W / mK-9 W / mK, 10 W / mK-20 W / mK, 20 W / mK-30 W / mK, 30 W / mK-40 W / mK, 40 W / mK-50 W / mK, 50 W / mK-60 W / mK, 70 W / mK-80 W / mK, 80 W / mK-90 W / mK, or 90 W / mK-100 W / mK. In addition, the low thermal conductivity material of the pool body 50 may be at least one-tenth the thermal conductivity of the relatively high thermal conductivity material surrounding the pool body 50.

[0019] As previously mentioned, optional chemically inert materials with low thermal conductivity include some nickel-molybdenum and nickel-chromium-molybdenum alloys or titanium, as well as tantalum. Other embodiments of chemically inert materials with low thermal conductivity include stainless steel or other nickel-based alloys. In an exemplary embodiment, the pool body 50 is constructed of HASTELLOY C-class alloys (e.g., Haynes International brand alloys C-4, C-22, C-22HS, C-276, and C-2000).

[0020] Figure 3 It shows Figure 2 Detailed view of the surrounding area K. The pool body 50 has, as shown... Figure 3The diagram shows a very thin wall. A very thin wall or thin wall can refer to the wall of the pool body 50 made of a chemically inert, low thermal conductivity material (e.g., a thin wall). The wall thickness of the pool body 50 can be as thin as possible while maintaining the structural integrity of the pool body 50 (e.g., maintaining sufficient rigidity). The wall thickness of the pool body 50 can be less than 1 / 16 of an inch (1.5875 mm). In other embodiments, the thin-walled pool body 50 can have a wall thickness of less than 1 / 32 of an inch (0.7938 mm). In an exemplary embodiment, the wall thickness of the very thin-walled pool body 50 can be between 0.02 inches and 0.01 inches (0.508 mm–0.254 mm), or less than ten-thousandths of an inch. Constructing one or more walls of the pool body 50 with a small thickness reduces the path length between the internal region 57 and the outer surface of the pool body 50. For example, heat conducted through the walls of the pool body 50 has a very short path length through the low thermal conductivity material of the pool body 50. Heat is conducted through the thin walls of the pool body 50 to a high thermal conductivity layer 70. For example, the high thermal conductivity layer 70 may be attached, adhered, fastened, molded, or otherwise bonded to the pool body 50. The high thermal conductivity layer may be a separate layer or wrapping attached to the outer surface of the pool body. The layer may surround or partially surround the pool body.

[0021] When a titrant containing the second substance is injected into the inner region 57 of the cell body 50, the heat generated by the exothermic reaction of the first substance (e.g., the sample solution) and the second substance is conducted along a short path length of the thin-walled, chemically inert, and low-thermal-conductivity cell body 50, and then reaches the sensor 11 between the sample cell 100 and the reference cell 200 through the high-thermal-conductivity layer 70. Additionally, the layer 70 may surround or partially surround the cell body 50 such that, after the titrant containing the second substance is injected into the inner region 57 of the cell body 50, the heat applied by the thermostat 80 to restore the equilibrium temperature between the sample cell temperature and the reference cell temperature is conducted along the short path length of the thin-walled, chemically inert, and low-thermal-conductivity cell body 50 through the high-thermal-conductivity layer 70.

[0022] Layer 70 is made of a high thermal conductivity material, such as gold, silver, copper, or aluminum. Other high thermal conductivity materials can be metallic and non-metallic, including synthetic materials. An exemplary embodiment of the high thermal conductivity layer 70 may have a thermal conductivity greater than 100 W / mK. For example, the thermal conductivity of layer 70 may be at least 10 times that of the low thermal conductivity pool body 50. In other exemplary embodiments, the thermal conductivity of layer 70 may be greater than 100 W / mK, greater than 200 W / mK, greater than 300 W / mK, or greater than 400 W / mK. Furthermore, layer 70 may have a thickness or wall thickness greater than 0.02 inches (0.508 mm). In an exemplary embodiment, layer 70 may have a thickness between 0.02 inches (0.508 mm) and 0.1 inches (2.54 mm). The thickness ratio between the thickness of layer 70 and the wall thickness of pool body 50 may be between 1:1 and 100:1.

[0023] Optionally, for example, the pool body 50 has a gold layer 70 attached to the pool body 50, wherein at least a portion of the pool body 50 has a thickness between 0.01 inches and 0.02 inches, and the thickness of the gold layer 70 attached to the pool body 50 is greater than 0.02 inches.

[0024] See again Figure 2 The sample cell 100 may include an access tube 55. Embodiments of the cell body 50 may attach, fasten, attach, or in other words, connect to the access tube 55. The access tube 55 may be a tube, cylinder, passage, connection, fitting, conduit, channel, etc., and may have a generally axial opening therethrough. In ITC applications, the access tube 55 may be configured to receive a blade 14 (shown in…) that passes through the access tube 55 and extends into the sample cell 100. Figure 7 A titrant containing a second substance for reacting with the sample solution within sample cell 100 may be injected into the sample cell via inlet tube 55. Furthermore, embodiments of inlet tube 55 may have thermal and mechanical contact with thermostat 80. For example, without the conductive lines 20a, 20b described in more detail below, the sole connection between sample cell 100 and thermostat 80 may pass through inlet tube 55. In an exemplary embodiment, inlet tube 55 may be made of the same material as cell body 50, such as a nickel-molybdenum alloy.

[0025] Additionally, the calorimeter 300 may include a reference cell 200. Embodiments of the reference cell 200 may also include a cell body and an inlet tube. The cell body of the reference cell may be a main body portion, a structural component forming the reference cell, a component for containing a reference substance, a reservoir, container, etc. Embodiments of the cell body of the reference cell may be cylindrical, such as in ITC applications, or may be an enclosed capillary cell, such as in DSC applications. The cell body of the reference cell may be configured to receive a liquid reference substance in an internal region of the reference cell 200. In exemplary embodiments, the reference cell 200 may include the same or substantially the same construction as the sample cell 100, as described above. For example, the reference cell 200 may include a cell body made of a chemically inert, low thermal conductivity material, wherein layers or portions of a high thermal conductivity material (such as gold, aluminum, or copper) are attached to the cell body of the reference cell.

[0026] Figure 4 A perspective view of a calorimeter configuration according to an embodiment of the invention, showing conductive lines 20a and 20b connected to calorimeter cells 100 and 200, is shown. As described above, without the first conductive line 20a and the second conductive line 20b, the only connection to the thermostat 80 passes through the inlet tube 55, resulting in a longer thermal equilibrium period than desired after loading a new sample. To address this problem, the calorimeter 300 may employ two conductive lines 20a and 20b connecting a high thermal conductivity layer 70 to the thermostat of the calorimeter 300.

[0027] A thermostat, such as the thermostat 80 shown in the attached figures, may include a diffusion adhesive block, wherein the diffusion adhesive block may include a plurality of diffusion adhesive layers 80a, 80b, 80c. Figure 1 In the thermostat 80, three diffusion adhesive layers 80a, 80b, and 80c are included. However, the thermostat 80 may include more than three adhesive layers, such as layers 80a, 80b, 80c, 80d, and 80e, as... Figure 7 As shown. An embodiment of the thermostat 80 may include a temperature sensor 89 disposed within the diffusion bonding block for measuring the temperature of the diffusion bonding block. The thermostat of the calorimeter 300 may be a component of a temperature control subsystem, temperature controller, temperature regulating device, etc., capable of controlling the temperature of the calorimeter block (e.g., the diffusion bonding block shown in the figures) to which the pools 100 and 200 can be mounted. The temperature of the thermostat may be measured by a temperature sensor within the thermostat and a temperature measurement module associated with the calorimeter computer. The output of the temperature measurement module may be provided via an electrical connection as input to a temperature control algorithm in the temperature control software of the calorimeter computer, enabling the temperature control algorithm to control the temperature of the thermostat. An embodiment of the thermostat of the calorimeter 300 may be connected to a temperature subsystem comprising multiple temperature control layers / modules.

[0028] In an exemplary embodiment, a first end 21a of the first conductive wire 20a may be connected (e.g., welded) to the surface of the thermostat 80 of the calorimeter 300, and a second end 22a of the first conductive wire 20a may be connected (e.g., welded) to the surface of layer 70 of the sample cell 100. Similarly, a first end 21b of the second conductive wire 20b may be connected (e.g., welded) to the surface of the thermostat 80 of the calorimeter 300, and a second end 22b of the second conductive wire 20b may be connected (e.g., welded) to the surface of the high thermal conductivity layer of the reference cell 200. In an exemplary embodiment, the first ends 21a of the first conductive wire 20a and the first ends 21b of the second conductive wire 20b are connected to the thermostat 80 at the same location on the thermostat 80. In other specific embodiments, the first ends 21a of the first conductive wire 20a and the first ends 21b of the second conductive wire 20b are gathered together to be wrapped or, in other words, joined together before being connected to the thermostat 80. Connecting wires 20a and 20b to the same location on the surface of thermostat 80 allows any thermal noise traveling through wires 20a and 20b to be detected as the same thermal noise peak. Alternatively, ends 21a and 21b may be connected to thermostat 80 at different locations along the surface of thermostat 80. In an exemplary embodiment, conductors 20a and 20b may be wrapped with insulating material or otherwise insulated to prevent or impede heat loss from conductors 20 and 20b.

[0029] The first conductive line 20a and the second conductive line 20b can provide sufficient heat conduction between the thermostat 80 and the sample cell 100 and the reference cell 200, respectively, to allow for a reasonable equilibrium time. For example, the conductive lines 20a and 20b can establish a high thermal conductivity path directly from the thermostat 80 to the cells 100 and 200, and specifically, be attached to a high thermal conductivity layer of the cell body, rather than relying solely on a thermal conduction path across the inlet pipe and cell body 50, which includes a chemically inert, low thermal conductivity material. By conducting heat through the wires 20a and 20b of a high thermal conductivity material (e.g., copper) in a direct path from the thermostat 80 to the cells 100 and 200, the time required to provide the necessary heat after the reaction in the sample cell 100 to restore the equilibrium temperature between the cells 100 and 200 can be reduced. In other words, connecting the thermostat 80 to the conduction lines 20a and 20b of the pools 100 and 200 avoids potential time delays when conducting heat over long paths in materials with low thermal conductivity, such as nickel-based alloys. Furthermore, the embodiment of the calorimeter 300 can utilize a common source for potential noise, allowing differential subtraction of thermal noise transmitted through conduction lines 20a and 20b, thus preventing adverse effects on the calorimeter signal.

[0030] Therefore, embodiments of the calorimeter 300 may include one or more mixed calorimeter cells, such as one or more sample cells 100 and one or more reference cells 200. The mixed calorimeter cells utilize the advantages of a chemically inert material used as the cell body, but also address the problems associated with the low thermal conductivity of the chemically inert material by linking a high thermal conductivity material to the chemically inert material. Furthermore, the conductive lines 20a and 20b also address the problem of delayed equilibrium time associated with chemically inert materials with low thermal conductivity (such as alloys already described). Figure 5 A graph illustrating an embodiment according to the invention is shown, demonstrating the advantage of the equilibration time of the added conductive line 20a for sample cell 100. Line 31 refers to a gold sample cell configuration, line 32 refers to a mixed sample cell 100 configuration with conductive line 20a, and line 33 refers to a sample cell configuration without conductive lines connecting the cell to the thermostat 80, wherein the sample cell is optionally constructed of a Hastelloy alloy. Figure 5 As shown in the graph, the time to reach a stable baseline for the mixing cell 100 with conductor 20a (i.e., the expected shorter baseline stabilization time, since a stable baseline represents equilibrium) is very close to the baseline stabilization time for the gold sample cell without conductor 20a. However, the mixing cell 100 also benefits from the advantage of a chemically inert sample cell body. A chemically inert cell body without conductor 20a requires at least twice as long to reach the same stable baseline or equilibrium as the mixing cell 100. Figure 6 A graph illustrating an embodiment according to the invention is shown, demonstrating the advantages of the thermally conductive layer 70 on the exterior of the sample cell body 50. Line 34 refers to a gold sample cell with a 10 µJ heater pulse; lines 35, 35', and 35" refer to sample cells (e.g., cell body 50) with silver (e.g., layer 70) attached externally to improve thermal conductivity with heater pulses of various sizes ranging from 0.5 µJ to 8 µJ; and line 36 refers to a sample cell excluding silver with a 10 µJ heater pulse, wherein the sample cell is constructed of a Hastelloy alloy. Figure 6 In the figure shown, narrower peaks are desirable. As can be seen in the data, the silver inclusions around the cell body 50 show a significantly reduced peak width compared to the cell body without silver inclusions, and have a peak width comparable to the gold sample cell. Therefore, the hybrid calorimeter cell addresses the issue associated with the low thermal conductivity of cells made of Hastelloy alloys, while retaining their chemical inertness.

[0031] Figure 7A schematic diagram of a calorimeter 300, which can utilize calorimeter cells 100 and 200 according to an embodiment of the present invention, is shown. The calorimeter 300 can use power compensation to measure the differential heat flux to / from the sample cell 100 compared to the heat to / from the reference cell 200. In other embodiments, the calorimeter 300 can measure the differential heat flux to / from the sample cell 100 relative to the reference cell 200. Embodiments of the calorimeter 300 may have three main subsystems communicating with the calorimeter 300: an injection control subsystem, a temperature control subsystem, and a power compensation subsystem.

[0032] The injection control subsystem may include a syringe or other substance delivery device for injecting aliquots of a titrant (such as a ligand) sample into a sample cell 100 containing the analyte. The syringe needle passes through a top space 85, a polymer block 84, a metal block 83, a heating and cooling device TED 81, and a thermostat 80 before entering the sample cell 100. The polymer block 84 may be, for example, a PEEK block or a nylon block. The metal block 83 may be, for example, an aluminum block. The thermostat 80 may be a diffusion-bonded block. The injection is performed via an electrical connection under the control of a stepper motor controller in a computer, which is connected to a calorimeter. A blade or paddle stirrer 14 at the tip of the syringe needle may be used to agitate the sample to ensure adequate mixing of the injected titrant with the analyte in the sample cell 100.

[0033] The temperature control subsystem may include heating and cooling TED 81, which can be controlled via a temperature control module and electrical connections using a temperature control algorithm. The temperature of the thermostat 80 can be measured by a temperature sensor within the thermostat 80 and a temperature measurement module. The output of the temperature measurement module can be provided via electrical connections as input to the temperature control algorithm in the calorimeter computer, enabling the temperature control algorithm to control the temperature of the thermostat 80.

[0034] The power compensation subsystem may include a sample cell 100, a reference cell 200, a cooling TED 13, and a sample heater, which are kept within a passive thermal shield 12. The temperature difference between the sample cell 100 and the reference cell 200 can be measured by the TED sensor 11. Figure 1 (As shown in the diagram). The sample cell 100 can be cooled by cooling TED 13 or heated by a heater. The signal from TED sensor 11 can be provided to a signal amplifier via an electrical connection, and the amplified signal can be used as input to a feedback control algorithm. The feedback control algorithm can control a power compensation module via an electrical connection to adjust the power to the sample heater so as to drive the temperature difference measured by TED sensor 11 to zero. The additional power required to drive the temperature difference to zero is used as a measure of the differential heat flux to the sample relative to a reference.

[0035] While this disclosure has been described in conjunction with the specific embodiments described above, it will be apparent to those skilled in the art that many alternatives, modifications, and variations will be readily apparent. Therefore, the preferred embodiments of this disclosure as described above are intended to be exemplary and not restrictive. Various changes may be made in accordance with the claims below without departing from the spirit and scope of the invention. The claims provide the scope of the invention and should not be limited to the specific examples provided herein.

Claims

1. A calorimeter, comprising: Sample cell; Reference pool; A thermostat in thermal communication with the sample cell and the reference cell; A first conductive line, the first conductive line having a first end connected to the thermostat and a second end connected to the sample cell; and The second conductive line has a first end connected to the thermostat and a second end connected to the reference pool.

2. The calorimeter according to claim 1, wherein the first end of the first conductive wire and the first end of the second conductive wire are each connected to the thermostat at the same position on the thermostat.

3. The calorimeter according to claim 1, wherein the first end of the first conductive wire and the first end of the second conductive wire are each connected to the thermostat at different positions on the thermostat.

4. The calorimeter according to claim 1, wherein the sample cell has a chemically inert cell body and a thermally conductive layer attached to the chemically inert cell body.

5. The calorimeter of claim 4, wherein the chemical inert cell body has a wall thickness of less than 0.0625 inches.

6. The calorimeter according to claim 4, wherein the second end of the first conductive wire is attached to the thermally conductive layer, and the thermally conductive layer is attached to the body of the sample cell.

7. The calorimeter according to claim 1, wherein the reference cell has a chemically inert cell body and a thermally conductive layer attached to the chemically inert cell body of the reference cell.

8. The calorimeter according to claim 7, wherein the second end of the second conductive wire is attached to the thermally conductive layer of the reference cell.

9. The calorimeter according to claim 1, further comprising: A thermoelectric sensor, wherein the thermoelectric sensor is positioned between the sample cell and the reference cell; A cooling thermoelectric device, the cooling thermoelectric device being connected to the sample cell; and A passive thermal shield encapsulates the sample cell, the reference cell, the thermoelectric sensor, and the cooling thermoelectric device.

10. The calorimeter according to claim 1, wherein the first conductive line and the second conductive line are each insulated by an insulating material to prevent heat loss from the first conductive line and the second conductive line.

11. A method comprising: Provide a calorimeter according to claim 1; as well as A high thermal conductivity path is established from the thermostat to the sample cell and the reference cell using the first and second conductive lines.

12. The method of claim 11, further comprising: The power of the sample heater in the sample cell is adjusted so that the temperature difference measured by the thermoelectric sensor positioned between the sample cell and the reference cell is driven to zero.

13. The method of claim 12, further comprising: The differential heat flow of the sample in the sample cell relative to the reference cell is measured by determining the additional power required to drive the temperature difference, as measured by a thermoelectric sensor positioned between the sample cell and the reference cell, to zero.

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