Chromatography system

Abstract

A chromatography system comprising a first pump, which is connectable or connected to a liquid reservoir for a first fluid, and a second pump, which is connectable or connected to a liquid reservoir for a second fluid, wherein a pump outlet line of the first pump and a pump outlet line of the second pump are connected to a connecting piece and after this connecting piece, as seen in the direction of flow, a chromatography column is provided, connected to the connecting piece by way of a connecting line, wherein temperature control of the fluids is provided by way of at least one of the lines that run between the pumps and the chromatography column, and before the chromatography column, as seen in the direction of flow, an adding unit is provided, wherein at least one heating device is provided for the temperature control of the fluids, wherein the heating device comprises a heat transfer unit, with a heating unit, and also a heating output controller, which is controllable in dependence on a temperature sensor, and the heating output controller is controllable in dependence on a volumetric flow of the fluid. The present invention also relates to a chromatography process in which the system is used and to a conversion kit.

Description

[0001] Chromatography system

[0002] The present invention relates to a chromatography system and a chromatography method.

[0003] Chromatographic techniques are important tools for identifying and separating complex samples. The basic principle underlying chromatographic techniques is the separation of a mixture into individual components by transporting the mixture in a moving fluid through a retentive medium. The moving fluid is typically referred to as the mobile phase, and the retentive medium is typically referred to as the stationary phase. The separation of the various constituents of the mixtures is based on differential partitioning between the mobile and stationary phases. Differences in the partition coefficient of the components lead to differential retention at the stationary phase, resulting in separation.

[0004] One of the advanced and now well-established chromatography methods is high-performance liquid chromatography (HPLC).

[0005] The temperature at which chromatography is performed has a significant influence on the separation performance of the process. A low temperature leads to high viscosity in many solvents, so very high pressure is required to achieve a sufficient solvent flow rate for a given column material particle size. On the other hand, many of the substances to be purified are unstable at excessively high temperatures, so the maximum temperature is limited.

[0006] Another problem is that the temperature of the solvent within the chromatography column should be kept as constant as possible to ensure good separation performance. Otherwise, the different solvent viscosities within the column can lead to slightly different retention times.

[0007] WO 03 / 029809 A1 and WO 2020 / 018902 A1 describe systems with solvent temperature control. Heating devices for heating solvents that can be used in chromatography systems are described, among others, in US 10,994,222 B2 and US 8,956,534 B2.

[0008] HPLC methods have been used for both analytical and preparative purposes for some time, and corresponding equipment is commercially available. However, there is a general desire to improve the properties of these systems and methods.

[0009] There is a particular interest in increasing the purity of the separated or purified substances. Furthermore, the loss of substances to be separated or purified caused by purification should be as low as possible. Furthermore, environmentally friendly solvents should be used wherever possible. Furthermore, the chromatography system or method should be capable of processing consecutive, possibly unrelated, samples as quickly as possible and without contamination from previous samples.

[0010] In view of the state of the art, it is therefore an object of the present invention to provide a chromatography system that solves the problems outlined above. In particular, the system should produce particularly pure products obtained with high yields. Furthermore, the system should have a high throughput, allowing various samples to be applied and purified in rapid succession without the need for complex purification cycles.

[0011] Furthermore, the substances to be separated should be able to exhibit the smallest possible runtime difference without negating their separation in the system. Furthermore, for a given runtime difference, the system should achieve the highest possible separation of the batches. In particular, the chromatography system should provide excellent separation so that very clear signals from the substances to be separated are obtained through detection.

[0012] A further objective is to provide a chromatography system that can be operated and manufactured with particularly low maintenance costs. The system should be as simple and cost-effective to operate as possible, resulting in further cost and manageability advantages.

[0013] Furthermore, the chromatography system should be as inexpensive as possible in relation to the volume flow at which it is operated.

[0014] Furthermore, the aim of this invention is to provide a method for performing chromatography that achieves the highest possible yield of purified substances. The separated substances should have the highest possible purity. Furthermore, the method should be as simple and cost-effective as possible, leading to further cost and manageability advantages.

[0015] Furthermore, a high yield and purity of the substances to be separated should be achievable for as many different liquid mixtures as possible. Furthermore, the chromatography system should be able to operate at different flow rates without negatively affecting other properties, such as separation performance.

[0016] Furthermore, it is an object of the present invention to provide components that enable the simplest possible conversion of a known HPLC system into one that enables solvent temperature control. This should also enable the conversion of preparative HPLC systems.

[0017] These and other objects not explicitly mentioned, but which can be readily derived or deduced from the contexts discussed in the introduction, are achieved by a chromatography system having all the features of patent claim 1.

[0018] The present invention accordingly relates to a chromatography system comprising a first pump, which is connectable or connected to a liquid reservoir for a first fluid, and a second pump, which is connectable or connected to a liquid reservoir for a second fluid, wherein a pump outlet line of the first pump and a pump outlet line of the second pump are connected to a connecting piece and, viewed in the flow direction, a chromatography column is provided downstream of this connecting piece, which is connected to the connecting piece via a connecting line, wherein temperature control of the fluids is provided via at least one of the lines arranged between the pumps and the chromatography column, and, viewed in the flow direction, an addition unit is provided upstream of the chromatography column, which is characterized in that at least one heating device is provided for temperature control of the fluids,wherein the heating device comprises a heat transfer unit with a heating unit and a heating power control which is controllable as a function of a temperature sensor and the heating power control is controllable as a function of a volume flow of the fluid.,

[0019] The present invention, in particular, ensures that particularly pure products are obtained with high yields. The present invention, in particular, enables the use of environmentally friendly solvents without having to accept any compromises due to reduced separation performance of the chromatography columns used. It should be noted here that the invention surprisingly allows extremely precise temperature control of the solvent. This allows sensitive substances to be separated at a relatively high temperature without the risk of them being degraded by excessively high temperatures. Similarly, temperature-sensitive column materials can be operated close to their maximum permissible temperature.A relatively high temperature, in turn, enables low viscosity, particularly in the case of environmentally friendly solvents, so that even column materials with a small particle size can be used at acceptable pressure. The small particle size is associated with a high separation efficiency of the column material. This high separation efficiency is achieved particularly with relatively small column volumes. Furthermore, the system features a high throughput, whereby different samples can be applied and purified in a rapid sequence without the need for complex cycles for cleaning and / or equilibrating the chromatography column. In particular, the reproducibility of cycles for cleaning and / or separating sample compositions increases significantly, so that peaks can be predicted with improved accuracy.

[0020] Particularly compared to other chromatography systems, an improvement has been achieved in that, for a given runtime difference, the chromatography system can achieve a very high separation of the batches. Furthermore, with a relatively small runtime difference between the substances to be separated, very good separation can be achieved in the chromatography system. In particular, very narrow signals of the substances to be separated are obtained during detection.

[0021] Very simply constructed pumps can also be used, thus achieving further investment cost advantages.

[0022] Furthermore, very good results are also achieved in chromatography processes in which the system is operated with a gradient.

[0023] Particularly surprising advantages can be achieved by the present invention in chromatography processes in which the different solvents cause a cooling or heating effect. Surprising improvements are achieved, for example, in chromatography processes in which water and acetonitrile are used as solvents, with the proportions of both solvents being varied so that they particularly preferentially form a gradient. The system according to the invention achieves exceptional separation accuracy when using different solvents that cause a cooling or heating effect.

[0024] The chromatography system according to the invention comprises a first pump and a second pump. The type of pump is irrelevant for the present invention. Rotary lobe pumps, centrifugal pumps, gear pumps, and piston pumps can be used. However, the invention enables the use of cost-effective piston pumps, which can preferably comprise at least two pistons. In piston pumps with at least two pistons, the two pistons can be controlled via a camshaft. Furthermore, the two pistons can be controlled independently of one another, whereby control via a camshaft is often more cost-effective and can be used for the purposes of the present invention. Preferably, the first pump and / or the second pump is designed as a piston pump, whereby the pump head is preferably coolable. The chromatography system comprises at least two pumps, although more than two pumps can also be used if necessary.

[0025] The present invention has the particularly surprising effect that excellent separation performance can be achieved even with cost-effective pumps.

[0026] The first pump is connectable or connected to a liquid reservoir for a first fluid, and a second pump is connectable or connected to a liquid reservoir for a second fluid. The type of liquid reservoir is not particularly limited but can be designed according to specific requirements.

[0027] The pump outlet lines of the first and second pumps are combined into a connector, and from this connector, they exit into a common outlet line. A chromatography column is provided downstream of this connector in the flow direction. Such connectors are known per se and are not subject to any particular limitations.

[0028] An addition unit is provided upstream of the chromatography column, viewed in the direction of flow. A sample to be separated is fed into the chromatography system via the addition unit. These addition units are known as such and are also referred to as sample dispensers. For example, the addition unit can be designed as an inlet point through which the sample can be added to the chromatography system. In a preferred embodiment, the addition unit comprises a sample loop and an injection valve, via which the sample loop can be connected to the connector.

[0029] The addition unit preferably comprises a sample loop into which a sample to be separated can be introduced. The sample loop can be connected in flow communication with one of the liquid reservoirs, preferably the first liquid reservoir, and the connecting piece. The sample loop can be supplied with a sample by means of positive or negative pressure. For example, it can be filled by injection. Furthermore, a sample vessel can be arranged upstream of a sample loop and a waste vessel downstream of the sample loop. A pump, for example a peristaltic or gear pump, is arranged between the sample loop and the waste vessel. This pump draws a sample from the sample vessel and transfers it into the sample loop. The volume of the sample loop can be selected according to requirements.Preferably, it can be provided that the volume of the sample loop is in the range of 0.5 ml to 30 ml, preferably in the range of 1 ml to 20 ml, particularly preferably in the range of 2.5 ml to 10 ml.

[0030] For example, suitable addition units are described in the documents DE 10 2008 006266 A1 , WO 2008 / 107562 A2, WO 2010 / 139359 A1 , DE 2020 / 16100451 U1 , WO 2018 / 128836 A1 and WO 2013 / 134222 A1, wherein for disclosure purposes the description of the addition units set out in these documents is incorporated into the present application by reference thereto.

[0031] Preferably, it can be provided that the addition unit comprises an injection valve, wherein the injection valve has at least two sample loop ports and two high-pressure ports for supplying and discharging fluid under high pressure.

[0032] The sample loop ports are preferably connected or connectable to a sample loop.

[0033] The sample loop can be fed using methods known from the prior art. For example, the sample loop can be accessed via connections that can be switched independently of the injection valve of the addition unit.

[0034] In a preferred embodiment, it can be provided that the injection valve has at least two sample loop ports, two high-pressure ports for supplying and discharging fluid under high pressure, and two ports for supplying and discharging sample composition and / or fluid into and out of the sample loop.

[0035] Furthermore, it can be provided that the addition unit is provided in front of the connecting piece as seen in the flow direction.

[0036] Preferably, it can be provided that one high-pressure port is connected to a line that is connected to the first pump and the other high-pressure port is connected to a line that is connected to the connecting piece.

[0037] Furthermore, it can be provided that the addition unit is provided after the first pump, seen in the flow direction.

[0038] Furthermore, it can be provided that the addition unit is provided after the connecting piece, seen in the direction of flow.

[0039] In addition, the addition unit can be provided to enable automatic addition of the samples into the chromatography system.

[0040] The chromatography system of the present invention has a temperature control system for the fluids, wherein the temperature control is carried out via at least one of the lines arranged between the pumps and the chromatography column. These lines are described above and below, and these lines include, in particular, the lines between the liquid reservoirs and the pumps, the pump outlet lines connected by a connector, and the connecting line between the connector and the chromatography column. At least one heating device is provided for temperature control of the fluids, wherein the heating device comprises a heat transfer unit with a heating unit and a heating power controller that is controllable as a function of a temperature sensor, and the heating power controller is controllable as a function of a volume flow of the fluid.The heating device can comprise one, two, or more heat transfer units, wherein at least one of the heat transfer units comprises a heating unit connected to a heating power controller that is controllable as a function of a temperature sensor, and the heating power controller is controllable as a function of a volume flow of the fluid. The number of heating devices results from the number of heating power controllers. If the heating powers or the transferred thermal energies of different heat transfer units, each having a heating unit, are controlled via exactly one heating power controller, the chromatography system has exactly one heating device. If the system comprises two or more heating power controllers, each connected to one or more heat transfer units, the chromatography system has two or more heating devices.In a preferred embodiment, it can be provided that the chromatography system comprises exactly one or exactly two heating devices, particularly preferably exactly one heating device.

[0041] This design allows the solvent temperature to be set to a specified value with surprising precision and maintained constant without the risk of overheating sensitive compounds. Furthermore, this design allows the chromatography system to be operated at widely varying flow rates without causing a significant drop in temperature. Furthermore, the heating device can be constructed very small, resulting in a narrow capillary lumen. This surprisingly improves separation efficiency, as the sample is applied to the column within a short time, thus minimizing diffusion within the capillary lumen.

[0042] Heating power is controlled as a function of the fluid's volume flow. Depending on the design, the volume flow of the first fluid, the second fluid, or the combined fluid flow downstream of the connecting piece can be used. Surprising advantages with regard to the system's operational reliability and separation performance can be achieved by using the volume flows of the first fluid and the second fluid upstream of the connecting piece to control the heating power.

[0043] The volume flow can be obtained by controlling the chromatography system, so that the heating power can be controlled via the control of the chromatography system depending on the pump power.

[0044] In principle, the heating output can be controlled according to the specifically measured volume flow or data provided by other components of the system, whereby the temperature of the heating unit can be measured at any location, for example at a core. Surprising advantages, which manifest themselves in particular in operational reliability and temperature accuracy, can be achieved by measuring the temperature of the fluid, whereby this preferably takes place in the region of the heat transfer unit or, viewed in the direction of flow, downstream of the heat transfer unit, particularly preferably downstream of the heat transfer unit and upstream of the chromatography column. In this embodiment, it is sufficient for heating output control to determine whether or not there is a volume flow of a fluid. A quantitative measurement of the volume flow of a fluid to control or regulate the heating output is not necessary here.If no or a very low volume flow is detected, which is insufficient for chromatography, the temperature of the heating unit can be limited to a specified value.

[0045] Surprising advantages can be achieved by locating the temperature sensor, which controls the heating power, near the heat transfer unit or downstream of the heat transfer unit in the direction of flow. This surprisingly ensures that the actual temperature of the solvent corresponds exactly to the specified temperature, preventing overheating of sensitive compounds.

[0046] Furthermore, it can be provided that the heat transfer unit has a capillary with a lumen, wherein the capillary can be heated with the heating unit, and the temperature sensor is arranged such that the temperature of the capillary can be measured, wherein the temperature can be measured at a point on the capillary which is provided after 50% of the length of the capillary as seen in the flow direction or the temperature can be measured at a point which is provided after the capillary as seen in the flow direction.

[0047] Preferably, the temperature sensor is provided upstream of the chromatography column in the flow direction.

[0048] In a further development, it can preferably be provided that the heating device is controllable via two temperature sensors, wherein a first temperature sensor is provided for determining a temperature of a line or a capillary and a second temperature sensor is provided via which a fluid flow can be determined, so that the heating power control can be controlled as a function of the volume flow of the fluid.

[0049] This design enables improved temperature control and represents a safety feature, as the volume flow of the fluid can be determined directly and thus errors in the chromatography system or operating errors can be detected immediately.

[0050] Particularly surprising advantages can be achieved by this embodiment of the present invention in chromatography processes in which the various solvents cause a cooling or heating of the mixture, as previously explained. With this embodiment of the invention, a complex calculation of the cooling of the mixture based on the mixing ratios and the volume flow can be dispensed with.

[0051] The temperature sensor, which can be used to determine a fluid flow, can be part of a calorimetric mass flow meter, among other things.

[0052] Preferably, it can be provided that the heating power control is programmed in such a way that no heating power is supplied to the first heating unit controllable via the heating power control if the second heating unit is operated with a heating power below a predetermined value.

[0053] In a preferred embodiment, the heating power control is designed as a closed-loop control, so that the heating power control can set the temperature of a heat transfer unit to a predetermined value. In particular, the heating power of the heating unit can be controlled such that the temperature measured by the sensor remains as constant as possible, preferably within a temperature range of less than 5°C, preferably within a temperature range of less than 2°C, and particularly preferably within a temperature range of less than 1°C.

[0054] In a preferred embodiment, the heating device can comprise two heat transfer units, each with a heating unit controllable via the heating power control, a first heat transfer unit with a first heating unit controllable via the heating power control, and a second heat transfer unit with a second heating unit controllable via the heating power control, and two temperature sensors are provided, wherein the second temperature sensor measures the temperature of the second heat transfer unit, which is arranged upstream of the first heat transfer unit in the flow direction. Preferably, the first heat transfer unit with a first heating unit controllable via the heating power control can be controlled via the measured values ​​of a first temperature sensor, wherein the first temperature sensor is provided for determining a temperature of a line or a capillary.This design surprisingly enables improved separation performance of the chromatography system. It should be noted that heat transfer via a capillary or a line is associated with a volume that results from the time the solvent remains within this capillary and the volume flow at which the chromatography is carried out. A small volume reduces the diffusion of the sample to be purified, but leads to very high heating power. The preferred design enables the solvents to be heated and mixed before the sample is injected, with the resulting cooling being minimized or compensated for by a heat transfer unit provided after sample addition.

[0055] Preferably, it can be provided that the heating power control of the second heating unit is controllable as a function of the volume flow of the fluid, wherein the heating power control is programmed such that the temperature of the second heat transfer unit or the second heating unit remains preferably substantially constant within a temperature range of less than 5°C. This configuration allows the volume flow of the fluid to be determined indirectly. Furthermore, this configuration enables an improvement in temperature control and represents a safety device, since the volume flow of the fluid can be determined without a pump power value or the like, thus allowing errors in the chromatography system or operating errors to be detected immediately.

[0056] Furthermore, it can be provided that the second heat transfer unit is located upstream of the addition unit, viewed in the flow direction, and the first heat transfer unit is located downstream of the addition unit. Preferably, the at least two heat transfer units are controllable via the heating power control, as previously explained.

[0057] Furthermore, it can preferably be provided that the first temperature sensor is provided upstream of the chromatography column as seen in the flow direction, wherein the first temperature sensor is provided for determining a temperature of a line or a capillary.

[0058] In a particularly preferred embodiment, it can be provided that the second heat transfer unit can heat two fluid streams with a second heating unit that can be controlled via the heating power control and is arranged upstream of the first heat transfer unit in the flow direction. This heat transfer unit can preferably comprise two capillaries, each of which enables the heating of a fluid. The two capillaries are preferably heated by a heating unit that can be controlled via the heating power control, thus simplifying temperature control. It can particularly preferably be provided that the two capillaries are wound around a core that is designed as a heating unit.

[0059] Furthermore, it can be provided that the heating device comprises three heat transfer units, each with a heating unit controllable via the heating power control, a first heat transfer unit with a first heating unit controllable via the heating power control, a second heat transfer unit with a second heating unit controllable via the heating power control and a third heat transfer unit with a third heating unit controllable via the heating power control, wherein the second and the third heat transfer unit are arranged upstream of the first heat transfer unit and preferably upstream of the connecting piece, viewed in the direction of flow, in order to heat the two fluid flows separately.

[0060] The heating device provided according to the invention for controlling the temperature of fluids comprises at least one heat transfer unit with a heating unit. Suitable heat transfer units comprising a heating unit are known from the prior art. Preferably, it can be provided that a heat transfer unit is used which comprises at least one capillary wound helically around a core, so that a capillary winding is formed, wherein the core serves as a heating unit and is electrically heatable, wherein the core is connected to the capillary, so that a connection exists between the core and the capillary, wherein the connection between the core and the capillary can be established by vacuum soldering. This heat transfer unit with a heating unit is novel and likewise the subject of the present invention.

[0061] Vacuum brazing is widely known in the industry. The process involves joining materials under reduced pressure. The vacuum reduces oxidation of the materials and the solder.

[0062] The heat transfer unit of the present invention can be manufactured cost-effectively and with high precision. Furthermore, the heat transfer unit exhibits exceptionally good heat transfer, allowing very large amounts of heat to be transferred over a short distance. This surprisingly makes it possible to design the chromatography system with an unusually compact design. Furthermore, the heat transfer unit exhibits very good efficiency, resulting in relatively low power losses.

[0063] In a preferred embodiment of the heat transfer unit with a heating unit according to the present invention, the heat transfer unit and the heating unit can be made of stainless steel. This design allows the chromatography system to be operated at very high pressures and with relatively aggressive solvents.

[0064] Stainless steel for the manufacture of the heat transfer unit and the heating unit is known to those skilled in the art. For example, stainless steel types V2A and V4A can be used, with types 1.4301, 1.4541, and 1.4307 (V2A) or 1.4401, 1.4571, and 1.4404 (V4A) being preferred. These types comply with European standards, with type 1.4404 (V4A) being particularly preferred.

[0065] Similar or identical stainless steel types are described internationally under the type designations AISI 316 and AISI 316L, although these types are also preferred. Furthermore, the capillary coil can be designed such that sections of the capillary are in contact. This results in a very compact heat transfer unit that transfers heat very efficiently to the solvent. In this case, the outer walls of the coil turns formed by the capillaries can be in contact.

[0066] Preferably, it can be provided that the core is a hollow circular cylinder and the heating unit is introduced into the inner recess of the hollow circular cylinder.

[0067] Furthermore, it can be provided that the capillary forms a capillary coil, wherein the capillary coil is single-layered, i.e., the capillary is wound around the core in only one layer. Preferably, the capillary is wound so tightly or densely that the capillaries touch each other during each turn (rotation of the capillary on the core), preferably over at least 50%, particularly preferably over the entire turn.

[0068] In a further development, it can be provided that the heat transfer unit comprises two capillaries. It can be provided particularly preferably that the two capillaries are wound around the core, so that two capillary windings are formed and the capillary windings are designed such that the two capillaries touch each other. This design can be viewed as a two-start screw, wherein the outer walls of the two turns of the coil formed by the capillaries touch each other. Furthermore, it can be provided that the two capillaries each form a capillary winding, wherein the capillary windings are single-layered. Preferably, the capillaries are wound so tightly or densely that the two capillaries touch each other on each turn (rotation of the capillaries on the core), preferably over at least 50%, particularly preferably over the entire turn.

[0069] Furthermore, it can be provided that the chromatography column and at least one heat transfer unit with a heating unit are arranged in a forced-air oven. The use of a forced-air oven can achieve surprising advantages. In addition to handling advantages, synergistic benefits arise in particular in improving the separation performance of the chromatography process.

[0070] Forced air ovens are widely known in the art, whereby this refers to generally known laboratory devices that are generally designed as a cabinet and have an interior whose interior temperature is kept essentially constant by an air flow. The ranges within which a forced air oven keeps the temperature constant correspond to those specified above and below for carrying out chromatography. This device can also be referred to as a heating cabinet with a forced air flow. Of course, a conventional heating cabinet, also called a drying cabinet, or a standard climate cabinet can also be used to accommodate a chromatography column and at least one heat transfer unit. However, the surprising advantages outlined above with regard to improving separation performance cannot be achieved with a conventional heating cabinet or a standard climate cabinet.

[0071] The size or the interior volume of the convection oven or a heating cabinet can be adapted to the needs and the space available in the laboratory. In a preferred embodiment, it can be provided that the convection oven or the heating cabinet has a volume into which 1 to 20, preferably 2 to 15 and particularly preferably 3 to 8 chromatography columns can be introduced. The chromatography columns can have a length in the range of 5 cm to 200 cm, preferably 10 cm to 100 cm and a diameter in the range of 1 cm to 10 cm, preferably 2 to 8 cm. It can preferably be provided that the convection oven or the heating cabinet has a volume in the range of 20 dm 3 up to 2 m 3 , preferably 35 dm 3 up to 1 m 3 has.

[0072] In a preferred further development, it can be provided that the circulating air oven comprises a Peltier element by means of which the circulating air oven can be heated.

[0073] Furthermore, the forced-air oven can be equipped with a leak sensor and / or a gas sensor. For better monitoring of the chromatography system, the forced-air oven can be equipped with a glass door. The previously described configurations can also be implemented using a heating cabinet.

[0074] Furthermore, it can be provided that the system can be used to carry out chromatography with a solvent gradient.

[0075] Preferably, it can be provided that the chromatography system can be controlled via a chromatography system control system.

[0076] Furthermore, the chromatography system can be provided with at least one detector. Preferably, the chromatography system can include a UV detector. Furthermore, the chromatography system can include a mass spectrometer as a detector. In a particularly preferred embodiment, the system comprises a UV detector and a mass spectrometer.

[0077] Furthermore, the chromatography system can have a fraction collector through which purified samples can be collected.

[0078] Preferably, the chromatography system may comprise an injection device with which samples can be automatically injected into the chromatography system.

[0079] Furthermore, it can be provided that the chromatography system comprises a chromatography system control which is in operative connection with a detector and a fraction collector.

[0080] Furthermore, it can be provided that the chromatography system comprises a chromatography system controller that is operatively connected to the first pump, wherein the pumping power of the first pump can be controlled via the chromatography system controller. Furthermore, the chromatography system controller can also be operatively connected to the second pump and control its pumping power. Furthermore, the chromatography system controller can be operatively connected to the heating power controller, so that the temperature specifications are made in the chromatography system controller. Depending on the design, the pumping powers transmitted to the pumps or the specified volume flows can be used to determine the volume flow of the fluid(s) in order to establish the heating power.

[0081] According to another aspect, a conversion kit is also provided by which a high-performance liquid chromatography (HPLC) system can be converted into a system according to the invention. Such a kit comprises at least two heat transfer units with a heating unit, wherein the heat transfer unit is described above as a novel article.

[0082] A further subject of the present invention is a method for carrying out chromatography comprising the use of a chromatography system according to the invention.

[0083] Preferably, it can be provided that the volume flow of the fluid is taken into account for regulating a heating output, wherein below a minimum volume flow of the fluid, the heating output is limited to a predetermined value.

[0084] Furthermore, it can be provided that a system is used, the heating device comprises two heat transfer units, each with a heating unit that can be controlled via the heating power control, a first heat transfer unit with a first heating unit that can be controlled via the heating power control and a second heat transfer unit with a second heating unit that can be controlled via the heating power control and the second temperature sensor measures the temperature of the second heat transfer unit, which is arranged upstream of the first heat transfer unit in the flow direction, wherein the volume flow of the fluid is determined via the heating power of the second heating unit that can be controlled via the heating power control, wherein if the heating power falls below a level that is necessary to maintain a temperature for the second heating unit, the heating power for the first heating unit is limited to a predetermined value.

[0085] The temperature of the second heat transfer unit can preferably be determined via a sensor that measures the temperature of the heating unit of the second heat transfer unit, for example, at a core serving as the heating unit. Preferably, a second heat transfer unit with two capillaries can be used, as described above and below. This allows for very high operational reliability, as the possibility of operating errors is minimized.

[0086] Furthermore, it can be provided that the chromatography system comprises a mixer for mixing the first fluid and the second fluid, which mixer is provided between the connecting piece and the chromatography column.

[0087] The mixer can be designed as an active or passive mixer. Surprising advantages can be achieved by using passive mixers. Special, unpredictable advantages can be achieved, in particular, by designing the mixer as a static mixer. Static mixers comprise flow-influencing elements that are incorporated into a body having an inlet and outlet. For example, a tubular body provided with inert particles can be used as a static mixer.

[0088] The volume of the mixer can be selected according to the user's needs, although this generally depends on the system's performance, such as the flow rate the system can provide. The higher the flow rate, the larger the volume of the preferred mixer. Furthermore, the mixer can have a volume in the range of 0.5 ml to 60 ml, preferably in the range of 1 ml to 30 ml.

[0089] In a preferred embodiment, it can be provided that the chromatography system comprises a mixer switching valve via which the mixer can be switched, wherein the mixer switching valve has at least two switching positions, wherein in a first position the mixer can be switched on and in a second position the mixer can be bridged.

[0090] Furthermore, it can be provided that the flow path of a fluid in the second position of the mixer switching valve, in which the mixer can be bypassed, is shorter than in the first position of the mixer switching valve, in which the mixer can be switched on. The flow path of a fluid results from the flow time for a given volume flow. Therefore, the flow path relates to the volume occupied by a fluid. Accordingly, the volume occupied by a fluid between the connecting piece and the chromatography column is smaller in the second position of the mixer switching valve, in which the mixer can be bypassed, than in the first position of the mixer switching valve, in which the mixer can be switched on.

[0091] The design of the mixer switching valve is not subject to any particular limitation and can be designed according to specific needs.

[0092] Preferably, the mixer switching valve can comprise at least four ports, two of which are connected to a mixer. Furthermore, one of the four ports of the mixer switching valve can be connected to a line connected to the connector, and one of the four ports of the mixer switching valve can be connected to a line connected to the chromatography column.

[0093] Preferably, it can be provided that when a sample to be separated is applied to the chromatography column, the mixer switching valve is switched to the second position and the fluid is passed around the mixer.

[0094] Furthermore, it can be provided that after a sample to be separated has been applied to the chromatography column, the mixer switching valve is switched to the first position and the fluid is passed through the mixer. During processes that serve to prepare the system for chromatography, for example, for cleaning the column or for temperature control, the mixer can preferably be switched on.

[0095] In a preferred embodiment, it can be provided that the second position of the mixer switching valve, in which the fluid is guided around the mixer, is selected to be as short as possible. This means that the time required for a sample to pass through the mixer switching valve is calculated in advance as accurately as possible, and the mixer switching valve is held in the second position for as short a time as possible in accordance with this calculation. In this calculation, the volume between the addition unit and the mixer switching valve, the addition volume of the sample as such, the volume of the mixer switching valve including the flow path for bypassing the mixer, and the volume flow must be taken into account, among other things. It can preferably be provided that the chromatography is carried out at a pressure in the range of 50 to 500 bar, preferably 75 to 400 bar.

[0096] In a preferred embodiment, the chromatography may be carried out at a temperature in the range of 40°C to 95°C, preferably 50°C to 80°C.

[0097] The detection of a fraction to be collected can be determined in a standard manner that is also generally used in related chromatography techniques. This includes, for example, collecting a fraction at a specific signal level of the detector, such as a UVA / IS detector. Furthermore, a fraction can also be collected based on a specific signal shape, such as a specified change in the slope of the detector signal or a specific value of the slope of the detector signal.

[0098] Furthermore, it can be provided that the chromatography is carried out at a volume flow in the range of 10 ml / min to 450 ml / min, particularly preferably in the range of 50 ml / min to 300 ml / min, and especially preferably 100 ml / min to 250 ml / min. This volume flow represents the total flow rate. The flow rate of the individual solvents, in particular of the first and second solvents, which are each used as a mixture, results from the respective volume fraction.

[0099] The solvents usable in the present chromatography system are generally known, and the process can be particularly distinguished by the use of environmentally friendly solvents. Environmentally friendly solvents include, in particular, water; alcohols such as methanol, ethanol, or propanol; aldehydes or ketones, preferably methyl ethyl ketone; esters, preferably ethyl acetate; or ethers, preferably tetrahydrofuran; aliphatic hydrocarbons, preferably hexane, cyclohexane, heptane, or pentane; and aromatic hydrocarbons, preferably benzene, toluene, or xylene. These compounds can be used individually or as a mixture. Furthermore, these compounds can be used as the first or second fluid to generate a solvent gradient.Furthermore, it can be provided that the fraction collector is controlled via a control unit and the control unit is operatively connected to the detector, wherein upon detection of a substance by the detector, a control pulse is sent to the fraction collector, which causes a change of the collection vessel.

[0100] In a further embodiment, the fraction collector can be controlled via a control unit, and the control unit can be operatively connected to the detector. After the detector has completed detecting a substance, a control pulse is sent to the fraction collector, causing a change of the collection vessel. This configuration is preferred over the embodiment in which a change of the collection vessel is initiated at the beginning.

[0101] Preferred embodiments of the present invention will be described below by way of example with reference to nine figures, without intending to limit the invention. They show:

[0102] Figure 1 is a schematic representation of a preferred chromatography system,

[0103] Figure 2 is a schematic representation of another preferred chromatography system,

[0104] Figure 3 is a schematic representation of another chromatography system,

[0105] Figure 4 is a schematic representation of a heating device,

[0106] Figure 5 is a schematic representation of a preferred heating device,

[0107] Figure 6 is a schematic representation of a preferred

[0108] Heat transfer unit with a heating unit for use in a chromatography system,

[0109] Figure 7 is a further schematic representation of a heat transfer unit with a heating unit for use in a chromatography system, Figure 8 is a schematic representation of a special heat transfer unit with a heating unit for use in a chromatography system,

[0110] Figure 9 is a further schematic representation of a special heat transfer unit with a heating unit for use in a chromatography system.

[0111] Figure 1 shows a schematic representation of a chromatography system (1) which is preferred.

[0112] A suitable chromatography system (1) comprises two fluid streams, wherein a first fluid is provided by a first liquid reservoir (3) and a second fluid is provided by a second liquid reservoir (5). The first fluid is transferred from the liquid reservoir (3) by a pump (7) via a heat transfer unit (11) with a heating unit into a connecting piece (17). Viewed in the direction of flow, an addition unit (15) is provided upstream of the connecting piece (17), said addition unit being arranged downstream of the pump (7) in the present embodiment. In a further embodiment, the addition unit (15) can also be arranged upstream of the pump (7).

[0113] The second fluid is transferred from the liquid reservoir (5) by a pump (9) via a heat transfer unit (13) with a heating unit into the previously described connecting piece (17). A mixer (19) is arranged downstream of the connecting piece (17) in the direction of flow. In a preferred embodiment, a mixer switching valve can be provided, via which the mixer (19) can be switched, so that the composition obtained downstream of the connecting piece (17) is mixed if the mixer (19) is switched on in a first position. In a second position of the mixer switching valve, the mixer (19) can be diverted.

[0114] In the present chromatography system (1), a heat transfer unit (21) with a heating unit and a chromatography column (23) are arranged downstream of the connecting piece (17) and the mixer (19). A detector (25) and a fraction collector (27) are preferably provided downstream of the chromatography column (23). In a preferred embodiment, the heat transfer units (11, 13, 21), each with a heating unit, the connecting piece (17), the mixer (19), and the chromatography column (23), among others, are located in a circulating air oven (29).

[0115] In the present embodiment illustrated in Figure 1, the heating power of at least one of the heating units of the heat transfer units (11, 13, 21) is controllable as a function of a volume flow of the fluid. Preferably, the heating power of the heating unit connected to or encompassed by the heat transfer unit (21) is controllable as a function of a volume flow of the fluid. The control is not explicitly illustrated for reasons of clarity. Heating devices with a heating power control system, which comprise one or more heat transfer units with a heating unit, are illustrated in Figures 4 and 5.

[0116] Figure 2 shows a schematic representation of a chromatography system (31), which is also preferred.

[0117] The chromatography system (31) shown in Figure 2, like the system (1) described above, uses two fluid streams. A first fluid is provided by a first liquid reservoir (33) and a second fluid by a second liquid reservoir (35). Both fluids are transferred to a connecting piece (45). For this purpose, the first fluid is pumped from the liquid reservoir (33) by a pump (37) via a pump outlet line (40) into a first capillary of the heat transfer unit (44) with a heating unit, and the second fluid is pumped from the liquid reservoir (35) by a pump (39) via a pump outlet line (42) into a second capillary of the heat transfer unit (44). Viewed in the direction of flow, a mixer (47) is provided downstream of the connecting piece (45).

[0118] In the present chromatography system (31), an addition unit (49) is arranged downstream of the mixer (47), followed by a heat transfer unit (51) with a heating unit, and then a chromatography column (53). A detector (55) and a fraction collector (57) are preferably provided downstream of the chromatography column (53). In a preferred embodiment, the heat transfer units (44, 51), each with a heating unit, the connecting piece (45), the mixer (49), and the chromatography column (53), among others, are located in a circulating air oven (59).

[0119] In the present embodiment illustrated in Figure 2, the heating power of at least one of the heating units of the heat transfer units (44, 51) is controllable as a function of a volume flow of the fluid. Preferably, the heating power of the heating unit connected to or encompassed by the heat transfer unit (51) is controllable as a function of a volume flow of the fluid. The control is not explicitly illustrated for reasons of clarity. Heating devices with a heating power control system, which comprise one or more heat transfer units with a heating unit, are illustrated in Figures 4 and 5.

[0120] For the sake of completeness, it should be noted that the embodiment shown in Figure 2 with a heat transfer unit with two capillaries is particularly preferred and the embodiment shown in Figure 1 can also be modified accordingly.

[0121] Figure 3 shows a schematic representation of a chromatography system (61), which is also preferred.

[0122] The chromatography system (61) shown in Figure 3 operates with two fluid streams, like the system (1) described above. A first fluid is provided by a first liquid reservoir (63) and a second fluid by a second liquid reservoir (65). Fluid is conveyed from the liquid reservoir (63) to a connecting piece (73) via a pump (67), and fluid is transferred from the liquid reservoir (65) via a pump (69). Viewed in the direction of flow, an addition unit (71) is provided upstream of the connecting piece (73), which in the present embodiment is arranged downstream of the pump (67). In a further embodiment, the addition unit (71) can also be arranged upstream of the pump (67). Viewed in the direction of flow downstream of the connecting piece (73), in this case, there is a mixer (75), followed by a heat transfer unit (77) with a heating unit, and then a chromatography column (79).The chromatography column (79) can be provided with a heating sleeve (not shown) to keep the temperature inside the chromatography column (79) constant. The heating power of the heating unit, which is connected to or encompassed by the heat transfer unit (77), is controllable as a function of a volume flow of the fluid. The control is not explicitly shown for reasons of clarity. Heating devices with a heating power control, which comprise one or more heat transfer units with a heating unit, are shown in Figures 4 and 5.

[0123] In the present case, a detector (81) and a fraction collector (83) are preferably provided downstream of the chromatography column (79).

[0124] Figure 4 shows a schematic representation of a heating device (100) which can be controlled as a function of a volume flow.

[0125] The heating device (100) comprises a heat transfer unit (102) with a heating unit (104), which is designed as a core in the present case, wherein the heat transfer unit (102) comprises a capillary (106) which is wound helically around a core, so that a capillary winding is formed.

[0126] The heating device (100) further comprises a heating power control (108) which is operatively connected to a temperature sensor (110) and a flow meter (112).

[0127] In the present embodiment, a fluid is first conducted via line (114) into the flow meter (112) and subsequently into the capillary (106) of the heat transfer unit (102). From the capillary (106), the fluid is transferred via line (114) into a chromatography column (116) and subsequently into further components of a chromatography system (not shown), as described in more detail herein, for example, in the previously illustrated Figures 1 to 3. The temperature sensor (110) is provided downstream of the heat transfer unit (102) and measures the temperature of the fluid in line (114). Alternatively, the temperature can also be measured in the region of the capillary (106), although measurement in the region of the capillary (106) is not preferred.

[0128] In the present case, the flow meter (112) is arranged upstream of the heat transfer unit (102) in the direction of flow. In an alternative embodiment, it can also be arranged downstream of the heat transfer unit (102), for example, downstream of the chromatography column (116). In a preferred embodiment, the flow meter (112) is designed as a calorimetric mass flow meter, so that the embodiment shown in Figure 4 has two temperature sensors, with this temperature sensor preferably being arranged upstream of the temperature sensor (110) in the direction of flow. Furthermore, it should be noted that further components of a chromatography system can be provided between the flow meter (112) and the heat transfer unit (102), as described in more detail herein, for example, in the previously shown Figures 1 to 3.

[0129] The fluid flow is measured by the flow meter (112) and transmitted to the heating power controller (108) via the measuring line (118). If no fluid is flowing through the line (114), i.e., the volume flow is very low, the heating power of the heat transfer unit (102) is controlled to a very low value; preferably, no heating power is output. If a volume flow is measured above a predetermined value, the temperature measured by the temperature sensor (110) via the measuring line (120) is evaluated to control the heating power, with the heating power controller (108) controlling the heating power of the heat transfer unit (102) via the control line (122).

[0130] Figure 5 shows a schematic representation of a preferred heating device (130) which can be controlled as a function of a volume flow.

[0131] The heating device (130) comprises a first heat transfer unit (132) with a heating unit (134). The heat transfer unit (132) comprises a capillary (136) wound helically around a core, wherein the core is heatable and serves as a heating unit (134).

[0132] Furthermore, the heating device (130) comprises a second heat transfer unit (138) which has a heating unit (140) and a capillary (142) and is constructed substantially the same as the first heat transfer unit (132).

[0133] The heating device (130) further comprises a heating power control (144) which is operatively connected to a temperature sensor (146) and the previously described heat transfer units (132, 138).

[0134] In the present embodiment, a fluid is first conducted via line (148) into the capillary (142) of the second heat transfer unit (138) and subsequently into the capillary (136) of the first heat transfer unit (132). Various components of a chromatography system, as previously shown, particularly in Figures 1 and 2, can be provided between the second heat transfer unit (138) and the first heat transfer unit (132). From the capillary (136), the fluid is conducted via line (148) into a chromatography column (150) and subsequently into further components (not shown) of a chromatography system, as described in more detail herein, for example, in Figures 1 to 3 previously shown.

[0135] The temperature sensor (146) is provided here after the first heat transfer unit (132) and measures the temperature of the fluid in line (148). Alternatively, the temperature can also be measured in the region of the capillary (136), although measurement in the region of the capillary (136) is not preferred.

[0136] The heating power of the second heat transfer unit (138), which is provided upstream of the first heat transfer unit (132) in the flow direction, is controlled via the control and measuring line (152). For this purpose, the temperature of the heating unit (140), which is preferably designed as a heatable core, is preferably measured via a temperature sensor, and the heating power is controlled by the heating power controller (144) via the control and measuring line (152) such that the temperature of the heating unit (140) remains as constant as possible, preferably within the previously stated temperature ranges.

[0137] The temperature of the fluid is measured by a temperature sensor (146) and transmitted to the heating power control (144) via a measuring line (154). The transmitted measured value is used to control the heating power of the first heat transfer unit (132) or the first heating unit (134).

[0138] If no fluid flows through line (148), the heating power of the heat transfer unit (138) is very low. Due to the low heating power of the second heat transfer unit (138), the volume flow in line (148) can be determined and the heating power of the first heat transfer unit (132) can be set to a very low value, with this control being carried out via the control line (156).

[0139] The second heat transfer unit (138) can be arranged upstream or downstream of the connecting piece (not shown in Figure 5) in the flow direction. Likewise, the second heat transfer unit (138) can be provided upstream or downstream of the addition unit (not shown in Figure 5) in the flow direction.

[0140] The second heat transfer unit (138) shown in Figure 5 preferably comprises a heating unit and two capillaries, so that both fluids are heated via the heating unit of the second heat transfer unit (138). In an embodiment not shown, the heating device (130) can comprise a third heat transfer unit. The mode of operation is analogous to the preceding embodiments. In this embodiment, the second heat transfer unit (138) or the third heat transfer unit (not shown) are each preferably arranged upstream of the connecting piece (not shown in Figure 5) in the flow direction in order to heat the two fluid streams separately.

[0141] Figure 6 shows a schematic representation of a preferably usable heat transfer unit (170). The heat transfer unit (170) comprises a capillary (172). The capillary (172) is wound around a core (174), thereby forming a capillary winding (176). The core (174) serves as a heating unit and is electrically heatable. Furthermore, the capillary (172) is provided with a temperature sensor (178), which can be used to measure the temperature of a liquid flowing through the capillary.

[0142] In the present embodiment, the sections of the capillary (172) touch each other through a tight capillary coil (176).

[0143] Figure 7 shows a schematic representation of a further embodiment of a preferably usable heat transfer unit (190).

[0144] The heat transfer unit (190) in this case comprises a capillary (192) wound around a core (194), thereby forming a capillary coil (196). The core (194) serves as a heating unit and can be electrically heated via a heating element (196), wherein the heating element (196) can be supplied with power via a line connection (200). Furthermore, the capillary (192) is provided with a temperature sensor (202) via which the temperature of a liquid flowing through the capillary can be measured, wherein the measured values ​​can be read out via the measuring line connection (204).

[0145] In the present embodiment, the sections of the capillary (192) touch each other through a tight capillary coil (196).

[0146] Figure 8 shows a schematic representation of a special heat transfer unit (210) which can be used with preference.

[0147] The heat transfer unit (210) in this case comprises two capillaries (212, 214), a first capillary (212) and a second capillary (214). The capillaries (212, 214) are wound around a core (216). The two capillaries (212, 214) each form a capillary winding (218, 220). In the present embodiment, the sections of the two capillaries (212, 214) touch each other through a tight winding, with sections of the first capillary (212) touching sections of the second capillary (214). The core (216) serves as a heating unit and is electrically heatable. Furthermore, the core (216) is provided with a temperature sensor (not shown) via which the temperature of the core (216) can be measured.

[0148] Figure 9 shows a schematic representation of a further embodiment of a special heat transfer unit (230) which can preferably be used.

[0149] The heat transfer unit (230) in this case comprises two capillaries (232, 234), a first capillary (232) and a second capillary (234). The capillaries (232, 234) are wound around a core (236). The two capillaries (232, 234) each form a capillary winding (238, 240). In the present embodiment, the sections of the two capillaries (232, 234) touch each other through a tight winding, with sections of the first capillary (232) touching sections of the second capillary (234). The core (236) serves as a heating unit and can be electrically heated via a heating element (242), wherein the heating element (242) can be supplied with power via a line connection (244). Furthermore, core (236) is provided with a temperature sensor (246) by means of which the temperature of core (236) can be measured, wherein the measured values ​​can be read out via measuring line connection (248).

[0150] The features of the invention disclosed in the foregoing description, as well as in the claims, figures and embodiments, may be essential both individually and in any combination for the realization of the invention in its various embodiments.

Claims

Patent claims 1. A chromatography system comprising a first pump, which is connectable or connected to a liquid reservoir for a first fluid, and a second pump, which is connectable or connected to a liquid reservoir for a second fluid, wherein a pump outlet line of the first pump and a pump outlet line of the second pump are connected to a connecting piece, and a chromatography column connected to the connecting piece via a connecting line is provided downstream of this connecting piece, as seen in the flow direction, wherein temperature control of the fluids is provided via at least one of the lines arranged between the pumps and the chromatography column, and an addition unit is provided upstream of the chromatography column as seen in the flow direction, characterized in that at least one heating device is provided for temperature control of the fluids,wherein the heating device comprises a heat transfer unit with a heating unit and a heating power control which is controllable as a function of a temperature sensor and the heating power control is controllable as a function of a volume flow of the fluid., 2. Chromatography system according to claim 1, characterized in that the temperature sensor, via which the heating power control can be controlled, is provided in the region of the heat transfer unit or, viewed in the direction of flow, after the heat transfer unit.

3. Chromatography system according to claim 1 or 2, characterized in that the heat transfer unit has a capillary with a lumen, wherein the capillary can be heated with the heating unit, and the temperature sensor is arranged so that the temperature of the capillary can be measured, wherein the temperature can be measured at a point on the capillary which is provided after 50% of the length of the capillary, viewed in the flow direction or the temperature can be measured at a point located downstream of the capillary in the direction of flow.

4. Chromatography system according to at least one of the preceding claims 1 to 3, characterized in that the heating device can be controlled via two temperature sensors, wherein a first temperature sensor is provided for determining a temperature of a line or a capillary and a second temperature sensor is provided via which a fluid flow can be determined, so that the heating power control can be controlled as a function of the volume flow of the fluid.

5. Chromatography system according to claim 4, characterized in that the heating device comprises two heat transfer units, each with a heating unit controllable via the heating power control, a first heat transfer unit with a first heating unit controllable via the heating power control and a second heat transfer unit with a second heating unit controllable via the heating power control and the second temperature sensor measures the temperature of the second heat transfer unit, which is arranged upstream of the first heat transfer unit in the flow direction.

6. Chromatography system according to claim 5, characterized in that the heating power control of the second heating unit is controllable as a function of the volume flow of the fluid, wherein the heating power control is programmed such that the temperature of the second heat transfer unit or the second heating unit remains substantially constant within a temperature range of less than 5°C.

7. Chromatography system according to claim 5 or 6, characterized in that the heating power control is programmed such that the first no heating power is supplied to the heating unit controllable by the heating power control if the second heating unit is operated with a heating power below a specified value.

8. Chromatography system according to at least one of the preceding claims 5 to 7, characterized in that the second heat transfer unit is provided upstream of the addition unit and the first heat transfer unit is provided downstream of the addition unit, as seen in the flow direction.

9. Chromatography system according to at least one of the preceding claims, characterized in that the chromatography column and at least one heat transfer unit with a heating unit are arranged in a circulating air oven.

10. Chromatography system according to claim 9, characterized in that the circulating air oven comprises a Peltier element by means of which the circulating air oven can be heated.

11. Chromatography system according to claim 9 or 10, characterized in that the circulating air oven is equipped with a leakage sensor and / or a gas sensor.

12. Chromatography system according to at least one of the preceding claims 9 to 11, characterized in that the circulating air oven is equipped with a glass door.

13. Chromatography system according to at least one of the preceding claims, characterized in that the chromatography system comprises a Mixer for mixing the first fluid and the second fluid, which is provided between the connector and the chromatography column.

14. Chromatography system according to claim 13, characterized in that the chromatography system comprises a mixer switching valve via which the mixer can be switched, wherein the mixer switching valve has at least two switching positions, wherein in a first position the mixer can be switched on and in a second position the mixer can be bridged.

15. Heat transfer unit with a heating unit for use in a chromatography system according to at least one of the preceding claims 1 to 14, characterized in that the heat transfer unit comprises at least one capillary which is wound helically around a core so that a capillary winding is formed, the core serving as a heating unit and being electrically heatable, the core being connected to the capillary so that a connection exists between core and capillary, the connection between core and capillary being able to be produced by vacuum soldering.

16. Heat transfer unit according to claim 15, characterized in that the heat transfer unit and the heating unit are made of stainless steel.

17. Heat transfer unit according to claim 15 or 16, characterized in that the capillary winding is designed such that there is contact between sections of the capillary.

18. Heat transfer unit according to at least one of the preceding claims 15 to 17, characterized in that the heat transfer unit comprises two capillaries.

19. Heat transfer unit according to claim 18, characterized in that the two capillaries are wound around the core so that two capillary windings are formed and the capillary windings are designed so that the two capillaries touch each other.

20. A method for carrying out chromatography comprising the use of a chromatography system according to at least one of the preceding claims 1 to 14.

21. Method according to claim 20, characterized in that the volume flow of the fluid is taken into account for regulating a heating power, wherein below a minimum volume flow of the fluid, the heating power is limited to a predetermined value.

22. Method according to claim 21, characterized in that the system according to at least one of the preceding claims 5 to 17 is used, wherein the volume flow of the fluid is determined via the heating power of the second heating unit which can be controlled via the heating power control, wherein if a heating power which is necessary to maintain a temperature for the second heating unit is not reached, the heating power for the first heating unit is limited to a predetermined value.

23. Conversion kit for converting a high-performance liquid chromatography system into a chromatography system according to at least one of the preceding claims 1 to 14, characterized in that the kit comprises at least two heat transfer units with a heating unit according to at least one of the preceding claims 15 to 19.

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