GB2603500A - Temperature control chamber for sample separation unit having heat exchanger with gas channelling - Google Patents

Abstract

A temperature control chamber 100 for controlling the temperature of a sample separation unit 30 (e.g. gas chromatography, HPLC, UPLC, SFC) comprises a heat exchanger 104 comprising at least one gas channel 106. The gas may be air and can be circulated in the temperature control chamber 132 by a ventilator 128 (e.g. a fan). Part of the temperature control chamber may be separated by a shielding structure 115 which protects it from the air flow. The heat exchanger may be directly coupled to a preheater 114, and indirectly coupled to the sample separation unit by a dovetail connector (116, figure 4). The heat exchanger may comprise a heating or cooling unit e.g. a Peltier element 126. The gas channels may have hexagonal cross-section or honeycomb structure (figure 4).

Description

DESCRIPTION

TEMPERATURE CONTROL CHAMBER FOR SAMPLE SEPARATION UNIT HAVING HEAT EXCHANGER WITH GAS CHANNELLING

BACKGROUND ART

[0001] The present invention relates to a temperature control chamber for and a method of controlling temperature of a sample separation unit of a sample separation apparatus for separating a fluidic sample in a mobile phase by the sample separation unit, and to a sample separation apparatus.

[0002] In liquid chromatography, a fluid (such as a mixture between a fluidic sample and a mobile phase) may be pumped through conduits and a column comprising a material (stationary phase) which is capable of separating different components of the fluidic sample. Such a material, so-called beads which may comprise silica gel, may be filled into a column which may be connected to other elements (like a sampling unit, a flow cell, containers including sample and/or buffers) by conduits.

[0003] For operating a sample separation apparatus, the fluid can be preheated by a preheater assembly located downstream of an injector for injecting the fluidic sample in the mobile phase and upstream of the column.

[0004] GB 2522059 discloses a preheater assembly for preheating a fluid, particularly in a fluid separation apparatus, comprises a capillary having a lumen and being configured for conducting the fluid, and a thermal coupling body contacting at least part of the capillary. The thermal coupling body has a thermal conductivity in a range between 8 W/(m K) and 100 W/(m K) and is arrangeable so that heat generated by a heat source is supplied to the capillary via at least part of the thermal coupling body. In another aspect, the thermal coupling body is made of plastic. A fluid separation apparatus is also disclosed which comprises a fluid drive unit for driving a fluid comprising the mobile phase and the fluidic sample in the mobile phase; a separation unit for separating the fluidic sample and the preheater assembly upstream of the separation unit.

[0005] US 2020/0292508 Al discloses a column oven which comprises a hollow -1 -AThr housing, an analysis column arranged in the housing and allowing circulation of a mobile phase in the analysis column, a heating portion configured to heat air, a swirl flow generation portion configured to discharge, as a swirl flow, the air heated by the heating portion into the housing, and a throttle portion configured to throttle the swirl flow when the swirl flow is discharged into the housing. The throttle portion has multiple through-holes formed to penetrate the throttle portion along a direction of discharging the swirl flow and arranged in a honeycomb shape as viewed from a swirl flow discharge side.

[0006] During a separation process, it may be necessary or desirable to bring the column to a desired temperature. For this purpose, the column is mounted in a column oven and heated there. Conventionally, such heating may be insufficient or may lack precision, which may have a negative impact on the accuracy of the separation result.

DISCLOSURE

[0007] It is an object of the invention to enable operation of a sample separation apparatus for separating a fluidic sample in a mobile phase to obtain a precise separation result. The object is solved by the independent claims Further embodiments are shown by the dependent claims.

[0008] According to an exemplary embodiment of the present invention, a temperature control chamber for controlling temperature of a sample separation unit of a sample separation apparatus for separating a fluidic sample in a mobile phase by the sample separation unit is provided, wherein the temperature control chamber comprises a heat exchanger comprising a thermally conductive material and having at least one gas channel, preferably a plurality of gas channels, through which gas is guidable.

[0009] According to another exemplary embodiment of the present invention, a sample separation apparatus for separating a fluidic sample is provided, wherein the sample separation apparatus comprises a fluid drive unit configured for driving a mobile phase and the fluidic sample injected in the mobile phase, a sample separation unit configured for separating the fluidic sample in the mobile phase, and a temperature control chamber having the above mentioned features and -2 -AThr accommodating the sample separation unit for controlling temperature of the sample separation unit [0010] According to still another exemplary embodiment, a method of controlling temperature of a sample separation unit of a sample separation apparatus for separating a fluidic sample in a mobile phase by the sample separation unit is provided, wherein the method comprises mounting the sample separation unit in a temperature control chamber which comprises a heat exchanger comprising a thermally conductive material and having at least one gas channel, preferably a plurality of gas channels, and guiding gas through the one or more gas channels.

[0011] In the context of this application, the term "temperature control chamber" may particularly denote a closed or closable room which may be delimited by an exterior casing and which may include functionality to control temperature of a sample separation unit mounted inside the temperature control chamber. Optionally, an additional preheating assembly may be mounted inside the temperature control chamber. In particular, the temperature control chamber may comprise functionality to thermally couple a sample separation unit mounted in the temperature control chamber with a heat source or a heat sink. For example, the temperature control chamber may be a column oven when the sample separation unit is a chromatographic separation column. In particular, the temperature control chamber may be an HPLC column compartment equipped with a heat exchanger with multiple integrated gas channels.

[0012] In the context of this application, the term "heat exchanger" may particularly denote a thermally effective member which may be capable of transferring thermal energy between a heat source or sink, gas guided through one or more gas channels of a thermally conductive body of the heat exchanger, and a sample separation unit (and in particular a fluid flowing through the sample separation unit) being thermally coupled with the heat exchanger and the gas. A heat exchanger may be used in both cooling and heating processes of fluid flowing through the sample separation unit. The thermally coupled fluids (i.e. the gas flowing through the one or more gas channels of the heat exchanger and the fluid flowing through the sample separation unit) may be physically separated by solid material of the sample separation unit.

[0013] In the context of this application, the term "thermally conductive material" -3 -AThr may particularly denote a material being capable of conducting heat. In particular, the thermally conductive material may have a thermal conductivity of at least 10 W/mK, in particular of at least 50 W/mK, and preferably of at least 100 W/mK. Examples of thermally conductive material which may be used for heat exchanging material of a heat exchanger may be aluminum, copper, or a ceramic.

[0014] In the context of this application, the term "gas channel" may particularly denote a hollow conduit, lumen or flow path inside the heat exchanger and being delimited partially or entirely by thermally conductive material so that gas flowing through the gas channel may be enabled for efficiently transferring thermal energy between the gas and the thermally conductive material of the heat exchanger. In particular, a heat exchanger may be equipped with one or preferably a plurality of enclosed air guides as gas channels. A gas channel formed in the heat exchanger may have an open inlet and an open outlet between which gas from an environment of the heat exchanger may enter the gas channel and may leave the heat exchanger to the environment of the heat exchanger, respectively. Different gas channels of a heat exchanger may be separate from each other so that gas flowing through one gas channel does not physically interact with gas flowing through another gas channel inside of the heat exchanger. Alternatively, it is also possible that different gas channels of the heat exchanger are in fluid communication with each other so that a bifurcated network of gas channels can be formed inside of the heat exchanger. Preferably, the gas channels may be internal gas channels extending through an interior of the heat exchanger. For instance, internal gas channels may be closed gas channels, which may be manufactured for instance by extrusion. For instance, the gas channels may be completely surrounded by metal, except at a bottom and top opening.

It is however also possible that at least sections of the gas channels are only partially surrounded by metal. Hence, the gas channels may be circumferentially closed or partially circumferentially open.

[0015] In the context of the present application, the term "sample separation apparatus" may particularly denote an apparatus which is configured for separating a fluidic sample, for instance into different fractions. In particular, the sample separation apparatus may be a chromatography apparatus. When the fluidic sample is supplied to the sample separation apparatus and is injected by an injector into a separation path -4 -AThr between fluid drive unit and sample separation unit, different physical, chemical and/or biological properties of different fractions of the fluidic sample may result in a separation of different fractions in the sample separation unit.

[0016] In the context of the present application, the term "fluid" may particularly denote a liquid and/or a gas, optionally comprising solid particles.

[0017] In the context of this application, the term "fluidic sample" (or sample fluid) may particularly denote any liquid and/or gaseous medium, optionally including also solid particles, which is to be separated. Such a fluidic sample may comprise a plurality of different molecules or particles which shall be separated, for instance small mass molecules or large mass biomolecules such as proteins. Separation of a fluidic sample may involve a certain separation criterion (such as mass, volume, chemical properties, etc.) according to which a separation is carried out.

[0018] In the context of this application, the term "mobile phase" may particularly denote any liquid and/or gaseous medium which may serve as fluidic carrier of the fluidic sample during separation. A mobile phase may be a solvent or a solvent composition (for instance composed of water and an organic solvent such as ethanol or acetonitrile). In an isocratic separation mode of a liquid chromatography apparatus, the mobile phase may have a constant composition over time. In a gradient mode, however, the composition of the mobile phase may be changed over time, in particular to desorb fractions of the fluidic sample which have previously been adsorbed to a stationary phase of a sample separation unit.

[0019] In the context of the present application, the term "fluid drive unit" may particularly denote an entity capable of driving a fluid, in particular the fluidic sample and/or the mobile phase. For instance, the fluid drive may be a pump (for instance embodied as piston pump or peristaltic pump) or another source of pressure. For instance, the fluid drive unit may be a high-pressure pump, for example capable of driving a fluid with a pressure of at least 100 bar, in particular at least 1000 bar.

[0020] The term "sample separation unit" may particularly denote a fluidic member through which a fluidic sample is transferred, and which is configured so that, upon conducting the fluidic sample through the separation unit, the fluidic sample will be -5 -AThr separated into different groups of molecules or particles. An example for a separation unit is a liquid chromatography column which is capable of trapping or retarding and selectively releasing different fractions of the fluidic sample. In particular, a sample separation unit may be a tubular body. For instance, a length of a sample separation unit may be in a range from 80 mm to 300 mm, for example 100 mm.

[0021] According to an exemplary embodiment, a temperature control chamber for temperature control of a sample separation unit (such as a chromatographic separation column) and fluid flowing through such a sample separation unit is provided, which may be implemented advantageously in a sample separation apparatus (such as a chromatographic sample separation apparatus, for instance an HPLC). Advantageously, such a temperature control chamber may be equipped with a heat exchanger having one or more internal but preferably open gas channels for guiding a gas flow through the heat exchanger for promoting heat exchange between the flowing gas and thermally conductive material of the heat exchanger and, in turn, also with the sample separation unit. The mentioned gas may be an atmosphere in the temperature control chamber. With such a design, thermal losses in the temperature control chamber may be kept very low, and a proper thermal energy transfer with respect to a sample separation unit, which may be mounted in the temperature control chamber, may be guaranteed. Descriptively speaking, gas (such as air) flowing through the one or more gas channels of the heat exchanger may exchange heat with the heat exchanger which may be transferred efficiently from the heat exchanger and the gas to a sample separation unit being thermally coupled therewith. The described gas channel design of the heat exchanger of the temperature control chamber may involve low manufacturing effort while simultaneously ensuring a precise temperature adjustment of fluid flowing through the sample separation unit.

[0022] In the following, further embodiments of the temperature control chamber, the method, and the sample separation apparatus will be explained.

[0023] In an embodiment, the one or more gas channels extend between an open inlet (preferably an open bottom) and an open outlet (preferably an open top) of the 30 heat exchanger. Hence, each gas channel may be open both at an inlet side and at an outlet side so that gas (such as air) in an interior of the temperature control chamber -6 -AThr may freely enter and leave the gas channels, thereby promoting a continuous and in particular circular gas flow.

[0024] In an embodiment, the one or more gas channels extend in parallel to each other. In other words, different portions of gas from the environment may flow simultaneously and in parallel through the gas channels. This may enhance the heat exchange between the gas and the heat exchanger, since the interaction area between gas and heat exchanger may become very high.

[0025] In an embodiment, the temperature control chamber is configured so that said gas is circulated in the temperature control chamber for controlling temperature of the sample separation unit. In other words, the arrangement of the heat exchanger with its gas channel(s) and the configuration of the temperature control chamber may be such that a closed loop path of the gas flow may be established. In other words, gas may flow from an inlet to an outlet of a respective gas channel of the heat exchanger and then along a geometrically definable trajectory within the temperature control chamber and back towards an inlet of a gas channel. The gas may repeatedly circulate along the described circular flow path. Thus, a continuous temperature control of a sample separation unit mounted in the temperature control chamber and being thermally coupled with the heat exchanger and the gas may be accomplished. This renders the temperature control of the sample separation unit efficient and precise.

[0026] In an embodiment, the heat exchanger comprises at least one preheater assembly mounting provision, in particular at least one substantially V-shaped recess, for mounting at least one preheater assembly for being directly thermally coupled with the heat exchanger, in particular dominated by heat conduction. Correspondingly, the temperature control chamber may comprise a preheater assembly being directly thermally coupled, in particular being in direct physical contact, with the heat exchanger and configured for thermally pre-treating the fluidic sample and/or the mobile phase upstream of the sample separation unit. A preheater assembly may be a member mounted in the temperature control chamber and being configured for preheating a fluidic sample and/or a mobile phase upstream of a sample separation unit through which the fluidic sample and/or mobile phase is to be guided after having passed the preheater assembly. The provision of a preheater assembly arranged -7 -AThr between an injector and the sample separation unit may ensure that the fluidic sample and/or mobile phase is at a desired target temperature when reaching the sample separation unit. For this purpose, the preheater assembly may comprise thermally conductive material establishing a thermal coupling between, on the one hand, the fluidic sample and/or or mobile phase flowing through the preheater assembly and, on the other hand, a heat source (which may be attached to the heat exchanger of the temperature control chamber). An outlet of the preheater assembly may then be fluidically connected with an inlet of the sample separation unit so that the preheated fluidic sample and/or mobile phase may enter at a predefined temperature the sample separation unit. For creating a highly efficient thermal connection between preheater assembly and heat exchanger, a heat exchanging surface of the preheater assembly may be mounted with direct physical contact at the thermally conductive material of the heat exchanger. Consequently, the heat exchange between the preheater assembly and the heat exchanger may be predominantly due to heat conduction, i.e. the direct microscopic exchange of kinetic energy of particles through the boundary between the two thermodynamic systems constituted by the heat exchanger and the preheater assembly Although heat convection and/or heat radiation may be additional heat transfer mechanisms between the heat exchanger and the preheater assembly, heat conduction may provide the largest contribution thanks to the direct physical contact between preheater assembly and heat exchanger. For accomplishing efficient heat conduction, the preheater assembly mounting provision of the heat exchanger on the one hand and the preheater assembly on the other hand may establish a form closure when the preheater assembly is mounted at the preheater assembly mounting provision. For instance, the preheater assembly may have a triangular cross-section which matches with a V-shaped recess of the preheater assembly mounting provision. When the preheater assembly is mounted at the preheater assembly mounting provision, two two-dimensional contact area portions may be formed at an interface between preheater assembly and preheater assembly mounting provision. Thus, a strong thermal coupling between the preheater assembly and the preheater assembly mounting provision may be established.

[0027] In an embodiment, the heat exchanger comprises at least one sample separation unit mounting provision, in particular at least one dovetail connector, for -8 -ADTnr mounting at least one sample separation unit for being indirectly thermally coupled with the heat exchanger, in particular dominated by at least one of heat radiation and heat convection. Hence, the temperature control chamber may be configured for mounting the sample separation unit for being indirectly thermally coupled with the heat exchanger, in particular for being decoupled from the heat exchanger concerning heat conduction. In particular, no or substantially no direct physical contact may be established between thermally conductive material of the heat exchanger and thermally conductive material of the sample separation unit. A minimum physical contact may only be caused by the task of mechanically mounting the sample separation unit at the heat exchanger. Thus, the thermai coupling between the preheater assembly and the preheater assembly mounting provision may be stronger than the thermal coupling between the sample separation unit and the separation unit mounting provision. The lack of a noteworthy direct thermal contact between sample separation unit and heat exchanger may suppress heat conduction, so that heat convection and/or heat radiation may be the dominant heat exchange mechanism(s) between sample separation unit and heat exchanger. Heat convection occurs when gas surrounding the sample separation unit and the heat exchanger carries heat along. Heat radiation may denote a transfer of energy by of photons or electromagnetic waves which may be emitted by a heated body such as the heat exchanger. Most preferably, the thermal coupling between heat exchanger and sample separation unit may be dominated by heat convection with additional contributions of heat radiation, rather than by direct heat conduction.

[0028] The sample separation unit may be arranged between injector and detector, or, if a preheater assembly is present, between preheater assembly and detector. The thermal coupling between the sample separation unit and the gas/heat exchanger may ensure that the fluidic sample and/or mobile phase is at a desired target temperature when flowing through the sample separation unit. For creating the desired weak thermal coupling between sample separation unit and heat exchanger, thermally conductive material of the sample separation unit may be mounted substantially without direct physical contact with thermally conductive material of the heat exchanger. For accomplishing a weak heat conduction, the sample separation unit mounting provision of the heat exchanger on the one hand and the sample separation -9 -ADTnr unit on the other hand may establish only a linear contact or a point contact when the sample separation unit is mounted at the sample separation unit mounting provision. Substantially an entire surface area of the sample separation unit may be in thermal contact with gas in the temperature control chamber.

[0029] In an embodiment, it is possible that a plurality of preheater assemblies and/or a plurality of sample separation units are mounted at the same time in the temperature control chamber. Each sample separation unit may be fluidically coupled with an assigned one of the preheater assemblies (if present), for instance by fluid conduits such as capillaries. A user or a control unit may select a pair of sample separation unit and assigned preheater assembly, or also a sample separation unit without preheater assembly, for executing a specific sample separation task.

[0030] In an embodiment, the temperature control chamber comprises a shielding structure delimiting a shielded space within which the sample separation unit is mounted or is to be mounted (in particular at a corresponding mounting provision) and being configured so that circulating gas flows around but not inside the shielding structure. Hence, a flow velocity of gas within the shielded space may be lower (in particular may be zero) than a flow velocity of gas around the shielded space. In particular, the sample separation unit may be arranged in a flow still volume of the temperature control chamber. Shielding the sample separation unit in the temperature control chamber with respect to a rapidly moving gas stream or gas flow (in particular shielding the sample separation unit from the gas flow through the one or more gas channels of the heat exchanger and further along a closed loop back to the heat exchanger) may allow to surround the sample separation unit with a substantially still gas atmosphere without pronounced gas dynamics or turbulence. It has turned out that such a static or homogeneous thermal environment of the sample separation unit may promote a homogeneous tempering of the sample separation unit and may have a positive impact on the accuracy of the sample separation. The shielding structure may for instance comprise a lid cooperating with the heat exchanger to provide a closed or substantially closed accommodation volume for the sample separation unit(s) (and optionally one or more preheater assemblies).

[0031] For instance, the shielding structure may form an at least partially closed -10 -AThr cage accommodating the sample separation unit. In an embodiment, a cage-shaped shielding structure is formed by one or more lid bodies and by the heat exchanger, which may also comprise opposing end plates forming pad of the shielding structure. Such a cage-shaped shielding structure may hermetically enclose the sample separation unit or may, which may be even more preferred, only partially enclose the sample separation unit to enable limited and precisely controllable gas communication between an interior and an exterior of the cage.

[0032] In an embodiment, the heat exchanger comprises a back wall, side walls and an open front side accessible and configured for accommodating one or more sample separation units and/or one or more preheater assemblies. The back wall of the heat exchanger may be actively heated or cooled, for instance by a heating and/or cooling unit attached to the back wall. The opposing front wall of the heat exchanger may be provided with mounting provisions for mounting one or more sample separation units and/or one or more preheater assemblies. The gas channel(s) may extend parallel to the front wall and to the back wall, and may extend essentially over the entire spatial range between front wall and back wall, so that the heat transfer between the streaming gas and the thermally conductive material of the heat exchanger may be highly efficient both on the front side, at the back side, and in between.

[0033] In an embodiment, the temperature control chamber comprises a heating and/or cooling unit thermally coupled with the heat exchanger and being configured for heating and/or cooling the heat exchanger. For example, such a heating and/or cooling unit may be attached to the heat exchanger. For heating, it is for instance possible to implement an ohmic heating unit. For cooling, it is for example possible to implement a liquid cooling unit using cool liquid as coolant. Advantageously, a Peltier element may be implemented as heating and/or cooling unit since, depending on an applied current or voltage characteristic, such a Peltier element may selectively heat or cool, as desired. It is also possible to provide a plurality of heating and/or cooling units at the temperature control chamber, and in particular at the heat exchanger.

[0034] In an embodiment, the heating and/or cooling unit is attached to the back wall, in particular to a flat back wall, of the heat exchanger, in particular at a vertical position of the back wall corresponding to a lower end of a sample separation unit AThr mounted at the heat exchanger. Such an arrangement is advantageous, since the back wall is free for receiving a heating and/or cooling unit. Furthermore, a heating and/or cooling unit arranged at the back wall of the heat exchanger may be sufficiently remote from the sample separation unit(s) which may be mounted at the opposing front side of the heat exchanger. As a result, highly undesired hot spots or cold spots at a sample separation unit mounted at the temperature control chamber may be reliably prevented. Such hot spots or cold spots, or more generally an inhomogeneous temperature distribution, at the sample separation unit may have a strongly disturbing impact on a sample separation process and the accuracy of its results. When the heating and/or cooling unit is attached to the back wall at a height level corresponding to a lower end of a mounted sample separation unit, insufficient heating may be prevented by the combinatory effect of the heated heat exchanger and gas flowing through the gas channels. Such a configuration may homogeneously heat the sample separation unit.

[0035] In an embodiment, the heating and/or cooling unit is a flat member, in particular a flat Peltier element. A flat heating and/or cooling unit may occupy a two-dimensional surface area of the back wall of the heat exchanger and will thereby promote additionally a homogeneous distribution of heating or cooling power from the heating and/or cooling unit to the heat exchanger. Hot spots or cool spots may then be reliably prevented.

[0036] In an embodiment, the temperature control chamber comprises a ventilator for ventilating gas to promote a gas flow into the one or more gas channels. Descriptively speaking, such a ventilator may move the gas and may promote entry of gas into the one or more gas channels. Thus, the ventilator may provide a driving force to the gas for promoting heat exchange. Furthermore, the gas motion triggered by a continuously operating ventilator may force the gas to circulate in a closed loop fashion along an interior of the temperature control chamber. Preferably, the ventilator is arranged at an inlet of the one or more gas channels of the heat exchanger to promote gas flow through the gas channel(s). This may additionally improve the heat exchange performance of the heat exchanger.

[0037] In an embodiment, the temperature control chamber comprises an exterior -12 -AThr casing accommodating the heat exchanger so that gas circulates within the casing along a closed circulation path which includes the one or more gas channels, and which in particular excludes the sample separation unit. The exterior casing may be partially or entirely closed circumferentially and may inhibit a flow of (in particular heated) gas out of the temperature control chamber. Advantageously, a closed flow path may be defined in an interior of the casing which preferably excludes a region around the mounted sample separation unit(s), and which includes the gas channels of the heat exchanger. More specifically, a central volume portion delimited by the casing may accommodate one or more sample separation units mounted at the heat exchanger and being excluded from pronounced gas flow by a shielding unit. Thus, the gas may be forced to flow along a closed trajectory delimited by the casing, the heat exchanger, the shielding unit and the one or more gas channels. Hence, the gas may be precisely guided to flow repeatedly and continuously around and separated from the sample separation unit(s) and through the gas channels of the heat exchanger.

[0038] In an embodiment, the heat exchanger is configured as a hollow metal body.

Such a hollow metal body may be manufactured with low effort, may have a high thermal conductivity, and may allow to simply define a plurality of gas channels. Preferably, a cross-section of the gas channels may be hexagonal. More specifically, the cross-section of the gas channels may have a honeycomb geometry. This may provide excellent mechanical stability and may simultaneously allow to form a large number of gas channels per volume of the hollow metal body, so that a highly efficient heat exchange may be obtained. As an alternative, the cross-section of the gas channels may also have another shape, such as a circular shape, a rectangular shape or any other polygonal shape.

[0039] In an embodiment, the heat exchanger consists of the thermally conductive material, in particular a metal, more particularly aluminum. Such a heat exchanger has a very high thermal conductivity and may be manufactured with low effort, for instance by metal extrusion.

[0040] In an embodiment, at least a central section of the heat exchanger between opposing open ends of the gas channels has a constant cross-sectional shape along an axial extension of the (in particular straight) gas channels. More specifically, apart -13 -AThr from opposing end plates of the heat exchanger contributing to the above-described shielding structure, the heat exchanger may have a constant cross-sectional shape along an entire extension of the gas channels between opposing open ends of the gas channels. Such a geometry may be manufactured by extrusion, so that the heat exchanger may comprise or may even consist of an extruded body.

[0041] In an embodiment, a cross-section of at least some of the gas channels has a hexagonal shape, in particular a honeycomb shape (i.e. a regular hexagonal shape with six edges or sides of constant length, wherein adjacent edges or sides enclose a 120° angle). Such a geometry allows to implement a large number of gas channels per volume of the heat exchanger and provides a mechanically strongly reinforced structure.

[0042] In an embodiment, the mounting device may comprise a preheater assembly (in particular directly) upstream of the sample separation unit. Such a preheater assembly may make it possible to bring the fluidic sample directly before its separation in the sample separation unit to an elevated (for instance target) temperature in order to create defined or favorable separation conditions.

[0043] The sample separation unit may be filled with a separating material. Such a separating material which may also be denoted as a stationary phase may be any material which allows an adjustable degree of interaction with a sample fluid so as to be capable of separating different components of such a sample fluid. The separating material may be a liquid chromatography column filling material or packing material comprising at least one of the group consisting of polystyrene, zeolite, polyvinylalcohol, polytetrafluorethylene, glass, polymeric powder, silicon dioxide, and silica gel, or any of above with chemically modified (coated, capped etc) surface.

However, any packing material can be used which has material properties allowing an analyte passing through this material to be separated into different components, for instance due to different kinds of interactions or affinities between the packing material and fractions of the analyte.

[0044] At least a part of the sample separation unit may be filled with a fluid separating material, wherein the fluid separating material may comprise beads having a size in the range of essentially 1 pm to essentially 50 pm. Thus, these beads may be -14 -ADTnr small particles which may be filled inside the separation section of the microfluidic device. The beads may have pores having a size in the range of essentially 0.01 pm to essentially 0.2 pm. The fluidic sample may be passed through the pores, wherein an interaction may occur between the fluidic sample and the pores.

[0045] The sample separation unit may be a chromatographic column for separating components of the fluidic sample. Therefore, exemplary embodiments may be particularly implemented in the context of a liquid chromatography apparatus.

[0046] The sample separation apparatus may be configured to conduct a liquid mobile phase through the sample separation unit. As an alternative to a liquid mobile phase, a gaseous mobile phase or a mobile phase including solid particles may be processed using the sample separation apparatus. Also materials being mixtures of different phases (solid, liquid, gaseous) may be processed using exemplary embodiments. The sample separation apparatus may be configured to conduct the mobile phase through the system with a high pressure, particularly of at least 600 bar, more particularly of at least 1200 bar.

[0047] The sample separation apparatus may be configured as a microfluidic device. The term "microfluidic device" may particularly denote a sample separation apparatus as described herein which allows to convey fluid through microchannels having a dimension in the order of magnitude of less than 500 pm, particularly less than 200 pm, more particularly less than 100 pm or less than 50 pm or less.

[0048] Exemplary embodiments of the sample separation apparatus may be implemented with a sample injector which may take up a sample fluid from a fluid container and may inject such a sample fluid in a conduit for supply to a separation column. During this procedure, the sample fluid may be compressed from, for instance, normal pressure to a higher pressure of, for instance several hundred bars or even 1000 bar and more. An autosampler may automatically inject a sample fluid from the vial into a sample loop. A tip or needle of the autosampler may dip into a fluid container, may suck fluid into the capillary and may then drive back into a seat to then, for instance via a switchable fluidic valve, inject the sample fluid towards a sample separation section of the liquid chromatography apparatus.

-15 -AThr [0049] The sample separation apparatus may be configured to analyze at least one physical, chemical and/or biological parameter of at least one component of the sample fluid in the mobile phase. The term "physical parameter" may particularly denote a size or a temperature of the fluid. The term "chemical parameter" may particularly denote a concentration of a fraction of the analyte, an affinity parameter, or the like. The term "biological parameter" may particularly denote a concentration of a protein, a gene or the like in a biochemical solution, a biological activity of a component, etc. [0050] The sample separation apparatus may be implemented in different technical environments, like a sensor device, a test device, a device for chemical, biological and/or pharmaceutical analysis, a capillary electrophoresis device, a liquid chromatography device, a gas chromatography device, an electronic measurement device, or a mass spectroscopy device. Particularly, the sample separation apparatus may be a High Performance Liquid device (HPLC) device by which different fractions of an analyte may be separated, examined and analyzed.

[0051] An embodiment of the present invention comprises a sample separation apparatus configured for separating compounds of a sample fluid in a mobile phase. The sample separation apparatus comprises a mobile phase drive, such as a pumping system, configured to drive the mobile phase through the sample separation apparatus. A sample separation unit, which can be a chromatographic column, is provided for separating compounds of the sample fluid in the mobile phase. The sample separation apparatus may further comprise a sample injector configured to introduce the sample fluid into the mobile phase, a detector configured to detect separated compounds of the sample fluid, a collector configured to collect separated compounds of the sample fluid, a data processing unit configured to process data received from the fluid separation system, and/or a degassing apparatus for degassing the mobile phase.

[0052] Embodiments may be implemented in conventionally available HPLC systems, such as the analytical Agilent 1290 Infinity II LC system or the Agilent 1290 Infinity II Preparative LC/MSD system (both provided by the applicant Agilent Technologies -see www.aqilent.com -which shall be incorporated herein by -16-ADTnr reference) [0053] One embodiment comprises a pumping apparatus having a piston for reciprocation in a pump working chamber to compress liquid in the pump working chamber to a high pressure at which compressibility of the liquid becomes noticeable. 5 One embodiment comprises two pumping apparatuses coupled either in a serial or parallel manner.

[0054] The mobile phase (or eluent) can be either a pure solvent or a mixture of different solvents. It can be chosen for instance to minimize the retention of the compounds of interest and/or the amount of mobile phase to run the chromatography.

The mobile phase can also been chosen so that the different compounds can be separated effectively. The mobile phase may comprise an organic solvent like for instance methanol or acetonitrile, often diluted with water. For gradient operation water and organic is delivered in separate bottles, from which the gradient pump delivers a programmed blend to the system. Other commonly used solvents may be isopropanol, THF, hexane, ethanol and/or any combination thereof or any combination of these with aforementioned solvents.

[0055] The sample fluid or fluidic sample may comprise any type of process liquid, natural sample like juice, body fluids like plasma or it may be the result of a reaction like from a fermentation broth.

[0056] The fluid is preferably a liquid but may also be or comprise a gas and/or a supercritical fluid (as for instance used in supercritical fluid chromatography -SFC).

BRIEF DESCRIPTION OF DRAWINGS

[0057] Other objects and many of the attendant advantages of embodiments of the present invention will be readily appreciated and become better understood by reference to the following more detailed description of embodiments in connection with the accompanied drawings. Features that are substantially or functionally equal or similar will be referred to by the same reference signs.

[0058] Figure 1 shows a sample separation apparatus in accordance with embodiments of the present invention, particularly used in high performance liquid -17 -AThr chromatography (H PLC) [0059] Figure 2 is a schematic illustration of a temperature control chamber for controlling temperature of a sample separation unit of a sample separation apparatus for separating a fluidic sample in a mobile phase by the sample separation unit 5 according to an exemplary embodiment.

[0060] Figure 3 is an exploded view of part of a temperature control chamber with a heat exchanger for controlling temperature of a sample separation unit of a sample separation apparatus for separating a fluidic sample in a mobile phase by the sample separation unit according to an exemplary embodiment.

[0061] Figure 4 shows a cross-sectional view of a heat exchanger of the type according to Figur 3.

[0062] Figure 5 shows a three-dimensional view of part of a heat exchanger of the type according to Figur 3.

[0063] Figure 6 shows a cross-sectional view of a heat exchanger of the type according to Figur 3.

[0064] The illustration in the drawing is schematically.

[0065] Before, referring to the figures, exemplary embodiments will be explained in further detail, some basic considerations will be explained based on which exemplary embodiments have been developed.

[0066] In conventional column ovens, a fan may be used to circulate the air inside the temperature control chamber. This shall provide a more homogeneous temperature distribution within the temperature control chamber. A mounting device holds the column in the air stream. A second device is used to heat/cool the air. High velocity is needed to achieve an equal heat distribution. However, such a high velocity may deteriorate the chromatographic result. With such conventional approaches, it may only be possible to achieve an average temperature inside the temperature control chamber, but not exactly a target temperature of the heating block.

[0067] Other conventional systems have a fan that circulates air from behind a -18 -AThr heating block to the front: As the back side is never ideally isolated, the air can only approximate the target temperature.

[0068] In order to overcome at least partially the above-mentioned and/or other conventional shortcomings, an exemplary embodiment of the invention provides a temperature control chamber where a gas (in particular air) circulation extends through one more gas channels of a heat exchanger which may also function as a column holder. Advantageously, the obtained temperature distribution may be more even, despite a low air speed.

[0069] According to an exemplary embodiment of the invention, a heat exchanger with one or more gas channels may be implemented in a temperature control chamber, such as a column oven, of a sample separation apparatus, such as a liquid chromatography apparatus. A sample separation unit, in particular a chromatographic separation column, may be mounted at and may be thermally coupled with a precisely defined degree at the heat exchanger. Gas flowing preferably along a closed loop path within the temperature control chamber and through the gas channels may homogeneously distribute heat provided by a heating unit to the heat exchanger and, via the gas flow, over an interior volume of the temperature control chamber. Descriptively speaking, the heat exchanger may temper the gas flowing through its gas channel(s), wherein the tempered gas may be used, in turn, for distributing thermal energy over the temperature control chamber and in particular for tempering the sample separation unit precisely and homogeneously. Thereby, also the sample separation unit may be heated homogeneously, and preferably without being in the stream of the flowing gas. In contrast to this, the sample separation unit may be mounted at the heat exchanger and may be surrounded by static or tranquilized gas.

Preferably, the sample separation unit may thus be only indirectly thermally coupled with the circulating gas and with the heat exchanger. This may ensure a homogeneous temperature of the entire sample separation unit which may have a positive impact on the accuracy of a sample separation result. By the provision of gas channels in the heat exchanger, a more homogeneous temperature distribution over the heat exchanger may be promoted as well, and in particular a cold back wall of the heat exchanger may be prevented. Furthermore, the channel structure in an interior of the heat exchanger may increase the heat exchange area and therefore the heat -19-AThr exchange performance of the heat exchanger. Furthermore, the provision of multiple gas channels in the heat exchanger may accelerate a thermal equilibrium, i.e. may ensure that substantially the entire heat exchanger may be brought more rapidly to a target temperature. Hence, a temperature equilibrium delay may be advantageously reduced. Beyond this, energy losses may be reduced so that the energy consumption during operation of the temperature control chamber may be reduced as well.

[0070] More specifically, a gist of an exemplary embodiment of the invention is to provide a heat exchanger embodied as a heating block for temperature control of a chromatographic column, the heating block being provided with internal (preferably circumferentially closed) gas channels. Gas, such as air, may be triggered to flow through -preferably in a closed loop inside of the temperature control chamber -the gas channels of the heat exchanger for providing temperature control. Thus, a heat exchanger with enclosed air guides may be provided for tempering a sample separation unit in a temperature control chamber of a sample separation apparatus.

[0071] As gas (such as air) may be guided internally through the heat exchanger, the temperature equilibration may be improved according to an exemplary embodiment of the invention. As the gas is not guided along an external wall, there is no heat loss to the outside. A surface of a heat exchanger wall for mounting one or more heater and/or cooling elements may be advantageously planar. Such a construction may save space and material.

[0072] The present inventors have found that a pronounced gas motion in the direct environment of a sample separation unit mounted in a temperature control chamber may unintentionally influence separation results, in particular chromatographic separation results. Hence, an exemplary embodiment of the invention arranges a sample separation unit apart from a gas flow within a temperature control chamber.

Furthermore, the sample separation unit may be indirectly heated by a heat exchanger of the temperature control chamber, in particular by heat convection rather than heat conduction. Thus, the sample separation unit may be only weakly thermally coupled with the heat exchanger and may be surrounded by a steady gas atmosphere, i.e. by gas which does not flow or stream at high speed around the sample separation unit. Thus, the surrounding air may provide the main heating energy impact on the sample -20 -AThr separation unit. More specifically, the heat exchanger may be actively heated, and the provided heat may be distributed by air flowing through gas channels of the heat exchanger. The sample separation unit may be mounted, weakly thermally coupled, on the heat exchanger and may be surrounded by a static air atmosphere. The circulating gas flow which also encompasses the gas channels of the heat exchanger may be shielded from the sample separation unit by a shielding structure or the like. Such a configuration allows a highly precise temperature adjustment of the sample separation unit without dynamic air flow related artefacts acting on the sample separation unit. By shielding the sample separation unit from the dynamic gas flow within the temperature control chamber, an accurate sample separation result (in particular a correct chromatogram) may be obtained. In order to suppress distortions of a thermal equilibrium, one or more preheater assemblies may be mounted as well on the heat exchanger of the temperature control chamber. Such a preheater assembly may be fluidically coupled with an assigned sample separation unit and may provide said sample separation unit with preheated mobile phase or fluidic sample. The degree of thermal coupling between preheater assembly and heat exchanger (which may be dominated by heat conduction due to a direct physical contact between heat exchanger and preheater assembly) may be higher than the degree of thermal coupling between sample separation unit and heat exchanger (which may be dominated by heat convection and/or heat radiation, rather than by heat conduction due to the lack of a noteworthy direct physical and thermal contact between heat exchanger and sample separation unit).

[0073] Referring now in greater detail to the drawings, Figure 1 depicts a general schematic of a liquid chromatography separation system as an example for a sample separation apparatus 10. A pump as an example for a fluid drive unit 20 receives a mobile phase from a solvent supply 25, typically via a degasser 27, which degases and thus reduces the amount of dissolved gases in the mobile phase. The fluid drive unit 20 -such as a high-pressure pump -drives the mobile phase through a sample separation unit 30 (such as a chromatographic column) comprising a stationary phase.

A sampling unit or injector 40 can be provided between the fluid drive unit 20 and the sample separation unit 30 in order to subject or add (often referred to as sample introduction) a sample fluid into the mobile phase. The stationary phase of the sample -21 -AThr separation unit 30 is configured for separating compounds of the sample liquid. A detector 50 is provided for detecting separated compounds of the sample fluid. A fractionating unit 60 can be provided for outputting separated compounds of sample fluid.

[0074] While the mobile phase can be comprised of one solvent only, it may also be mixed from plural solvents. Such mixing may be a low pressure mixing and provided upstream of the fluid drive unit 20, so that the fluid drive unit 20 already receives and pumps the mixed solvents as the mobile phase. Alternatively, the fluid drive unit 20 may be comprised of plural individual pumping units, with plural of the pumping units each receiving and pumping a different solvent or mixture, so that the mixing of the mobile phase (as received by the sample separation unit 30) occurs at high pressure und downstream of the fluid drive unit 20 (or as part thereof). The composition (mixture) of the mobile phase may be kept constant over time, the so-called isocratic mode, or varied over time, the so-called gradient mode.

[0075] A control unit 70, which can be a conventional PC or workstation, may be coupled (as indicated by dashed arrows) to one or more of the devices in the sample separation apparatus 10 in order to receive information and/or control operation. For example, the control unit 70 may control operation of the fluid drive unit 20 (for instance setting control parameters) and receive therefrom information regarding the actual working conditions (such as output pressure, flow rate, etc., at an outlet of the pump). The control unit 70 may also control operation of the solvent supply 25 (for instance setting the solvent/s or solvent mixture to be supplied) and/or the degasser 27 (for instance setting control parameters such as vacuum level) and may receive therefrom information regarding the actual working conditions (such as solvent composition supplied over time, flow rate, vacuum level, etc.). The control unit 70 may further control operation of the sampling unit or injector 40 (for instance controlling sample injection or synchronization sample injection with operating conditions of the fluid drive unit 20). The sample separation unit 30 may also be controlled by the control unit 70 (for instance selecting a specific flow path or column, setting operation temperature, etc.), and send -in return -information (for instance operating conditions) to the control unit 70. Accordingly, the detector 50 may be controlled by the control unit 70 (for instance with respect to spectral or wavelength settings, setting time -22 -AThr constants, start/stop data acquisition), and send information (for instance about the detected sample compounds) to the control unit 70. The control unit 70 may also control operation of the fractionating unit 60 (for instance in conjunction with data received from the detector 50) and provides data back.

[0076] In Figure 1 it can also be seen that the sample separation unit 30 (such as a chromatographic separation column) is arranged together with a preheater assembly 114 inside a temperature control chamber 100 (such as a column oven) and can be heated there using a heat source (not shown). The preheater assembly 114 may be thermally coupled stronger and the sample separation unit 30 may be thermally coupled weaker to a heat exchanger 104 which is arranged as well within the temperature control chamber 100. Mobile phase and/or fluidic sample may flow, driven by the fluid drive unit 20, into the temperature control chamber 100 and inside of the temperature control chamber 100 firstly through the preheater assembly 114 for bringing the fluid to a target temperature and subsequently through the heated sample separation unit 30 for sample separation. In this way, the sample separation unit 30 can be brought to a target or predetermined temperature which may be desired for a sample separation process.

[0077] The temperature control chamber 100 may be configured for controlling the temperature of the sample separation unit 30 of the sample separation apparatus 10 for separating a fluidic sample in a mobile phase by the sample separation unit 30.

Advantageously, the temperature control chamber 100 comprises heat exchanger 104 comprising a thermally conductive material and having one or more gas channels 106 through which gas is guidable. This allows a highly precise temperature adjustment of the fluidic sample and/or the mobile phase in the sample separation unit 30 in a simple way.

[0078] Figure 2 to Figure 6 describe preferred embodiments of temperature control chambers 100 with heat exchangers 104, which can be implemented for instance in the embodiment of Figure 1: [0079] Figure 2 is a schematic illustration of a temperature control chamber 100 for controlling temperature of a sample separation unit 30 of a sample separation apparatus 10 (as the one shown in Figure 1) for separating a fluidic sample in a mobile -23 -AThr phase by the sample separation unit 30 according to an exemplary embodiment.

[0080] The embodiment of Figure 2 provides a temperature control chamber 100, more specifically a column oven, for controlling temperature of a sample separation unit 30, such as a chromatographic separation column, of a sample separation apparatus 10, for instance a liquid chromatography device. Said temperature control chamber 100 may comprise a heat exchanger 104 for transferring heat to a flowing gas stream and is made of a thermally conductive material such as aluminum or copper. As shown, the heat exchanger 104 has (in the shown embodiment three) parallel gas channels 106 through which a gas, in particular air, is guidable simultaneously.

[0081] As shown, the gas channels 106 are open both on the bottom side and on the top side of the heat exchanger 104. More specifically, each of the gas channels 106 extends between an open bottom 108 and an open top 110 of the heat exchanger 104. The gas enters the gas channels 106 through the open bottom 108 and leaves the gas channels 106 through the open top 110. In the shown embodiment, the gas channels 106 extend in parallel to each other.

[0082] The illustrated temperature control chamber 100 is designed so that the gas is circulated in the temperature control chamber 100 so thereby control the temperature of the sample separation unit 30. As shown, the sample separation unit 30 is indirectly thermally coupled with the heat exchanger 104, preferably substantially without physical contact. More precisely, the sample separation unit 30 is thermally decoupled from the heat exchanger 104 concerning heat conduction, but is thermally coupled with the heat exchanger 104 in terms of heat convection and heat radiation.

[0083] In addition to the sample separation unit 30, also a preheater assembly 114 is mounted in the temperature control chamber 100 so as to be directly thermally coupled with direct physical contact with the heat exchanger 104. The preheater assembly 114 is configured for thermally pre-treating the fluidic sample and/or the mobile phase upstream of the sample separation unit 30. Preheater assembly 114 and sample separation unit 30 are fluid ically coupled by a fluid conduit such as a capillary (not shown) so that fluid being preheated by the preheater assembly 114 may be supplied subsequently to the sample separation unit 30.

-24 -AThr [0084] As shown, both the sample separation unit 30 and the preheater assembly 114, both being mounted on the heat exchanger 104, may be located in the central region of the temperature control chamber 100. An interior of the temperature control chamber 100 is delimited by an exterior surrounding casing 130. The heat exchanger 104 may be mounted at an inner wall of the casing 130. Both the sample separation unit 30 and the preheater assembly 114 are shielded from a moving gas flow by a circumferential cage constituted partially by the heat exchanger 104 and partially by a shielding structure 115. Due to this geometry, a closed circulation path 132 for the gas is formed, which encompasses the gas channels 106 and the gaps between the casing 130 and the shielded cage which encloses the sample separation unit 30 (and the optional preheater assembly 114). Thus, the temperature control chamber 100 comprises exterior casing 130 which accommodates the heat exchanger 104 so that gas circulates within the casing 130 along a closed circulation path 132 which includes the gas channels 106 and which excludes the sample separation unit 30.

Consequently, the sample separation unit 30 is shielded with respect to the dynamic gas flow and is surrounded by static gas within the shielded cage. Hence, the temperature control chamber 100 comprises a shielding structure 115, such as an at least partially closed cage accommodating the sample separation unit 30, delimiting a flow protected space 118 within which the sample separation unit 30 is arranged.

Consequently, circulating gas flows around but not inside the shielding structure 115.

Hence, the sample separation unit 30 is located in a flow still volume of the temperature control chamber 100.

[0085] Still referring to Figure 2, the shielding structure 115 may form a largely closed cage accommodating the sample separation unit 30 and the preheater assembly 114. As shown, the shielding structure 115 is formed by a lid structure and by the heat exchanger 104, which may also comprise opposing end plates forming part of the shielding structure 115. The shielding structure 115 delimits a gas flow protected volume or space 118. The cage-shaped shielding structure 115 may surround the sample separation unit 30 to limit gas communication between an interior and an exterior of the cage-shaped shielding structure 115.

[0086] As shown as well in Figure 2, the temperature control chamber 100 comprises a ventilator 128 for ventilating gas to promote a gas flow into the gas -25 -AThr channels 106. Preferably, the ventilator 128 is located at the open bottom 108 of the heat exchanger 104, i.e. at the inlet into the parallel flow channels 106. Descriptively speaking, the ventilator 128 may be arranged to blow gas into the gas channels 106.

[0087] The temperature control chamber 100 may also comprise a heating and/or cooling unit 126 (such as a planar Peltier element) which is thermally coupled with the heat exchanger 104 for heating and/or cooling the heat exchanger 104.

[0088] Figure 3 is an exploded view of part of a temperature control chamber 100 with a heat exchanger 104 for controlling temperature of a sample separation unit 30 of a sample separation apparatus 10 for separating a fluidic sample in a mobile phase by the sample separation unit 30 according to an exemplary embodiment. Figure 4 shows a cross-sectional view of a heat exchanger 104 of the type according to Figur 3. Figure 5 shows a three-dimensional view of part of a heat exchanger 104 of the type according to Figur 3. Figure 6 shows a cross-sectional view of a heat exchanger 104 of the type according to Figur 3.

[0089] As best seen in Figure 4, the heat exchanger 104 comprises a back wall 120, side walls 122 and an open front side 124 accessible and configured for accommodating a sample separation unit 30 and/or a preheater assembly 114.

[0090] Referring to Figure 3 and Figure 4, the heat exchanger 104 comprises preheater assembly mounting provisions 112 which are embodied as substantially V-shaped recesses with an angle a of 60°. Preheater assembly mounting provisions 112 are configured for mounting preheater assemblies 114, which may have a substantially triangular cross-section, as shown in Figure 3. For instance, such a preheater assembly 114 may comprise a thermally conductive body and a wound capillary with an interior fluid lumen thermally coupled with the thermally conductive body. When these preheater assemblies 114 are mounted at the preheater assembly mounting provisions 112, a direct physical contact along two two-dimensional contact areas may be established between an exterior surface of the preheater assemblies 114 and an exterior surface of the preheater assembly mounting provisions 112. Consequently, each preheater assembly 114 is directly thermally coupled with the heat exchanger 104, wherein a heat transfer from heat exchanger 104 to preheater assembly 114 may be accomplished predominantly by heat conduction, with possible additional -26 -AThr contributions from heat convection and heat radiation.

[0091] Still referring to Figure 3 and Figure 4, the heat exchanger 104 comprises sample separation unit mounting provisions 116 which are here embodied as dovetail connectors. When a sample separation unit 30 is mounted at such a dovetail connector, the sample separation unit 30 may be spaced with regard to a heat exchange surface of heat exchanger 104. Each of the sample separation unit mounting provisions 116 is configured for mounting a respective sample separation unit 30 for being only indirectly thermally coupled with the heat exchanger 104. This thermal coupling may be weak due to an only very small point contact or linear contact between sample separation unit 30 and sample separation mounting provisions 116.

As a result, essentially no heat conduction is possible between heat exchanger 104 and sample separation unit 30. In contrast to this, heat exchange between heat exchanger 104 and sample separation unit 30 may be dominated by heat radiation and/or heat convection.

[0092] As shown in Figure 4, the temperature control chamber 100 may comprise a heating and/or cooling unit 126 which is thermally coupled with the heat exchanger 104 for heating and/or cooling the heat exchanger 104. More specifically, the heating and/or cooling unit 126 is attached to the flat back wall 120 of the heat exchanger 104. Correspondingly, the heating and/or cooling unit 126 may also be a flat member to thereby create a high thermal exchange surface between heat exchanger 104 and heating and/or cooling unit 126 in a compact way. Preferably, the heating and/or cooling unit 126 may be a Peltier element which may be electrically controlled for selectively heating or cooling. As shown in Figure 3, the heating and/or cooling unit 126 is preferably mounted at a vertical position of the back wall 120 corresponding to a lower end of a sample separation unit 30 mounted at the heat exchanger 104. This ensures a homogeneous supply of heating energy. As shown with reference sign 115 in Figure 3, an isolation plate and a flowsheet may be provided.

[0093] As best seen in Figure 4, the heat exchanger 104 may be configured as a hollow metal body, for instance made of highly thermally conductive aluminum. As 30 shown in Figure 4 as well, some of the gas channels 106 may be embodied as hexagonal or honeycomb structures. This may make it possible to provide a very high -27 -AThr number of gas channels 106 per volume of the heat exchanger 104. When the heat exchanger 104 of Figure 4 is mounted on a casing 130 of a temperature control chamber 100, it may be oriented vertically, as shown in Figure 2.

[0094] Again referring to Figure 4, heat exchanger 104 is composed of a heating block with integrated gas channels 106 and is connected to a Peltier element as heating and/or cooling unit 126. The heat exchanger 104 is lightweight due to its high amount of empty volume. For instance, a ratio between the hollow volume of the gas channels 106 and the solid volume of the heat exchanger 104 may be at least 0.3. The heating block may be a metal block which may be manufactured preferably by extruding.

[0095] Referring to Figure 4 and Figure 5, a central section of the heat exchanger 104 between the opposing open ends 108, 110 of the gas channels 106 may have a constant cross-sectional shape along an extension of the gas channels 106, wherein the heat exchanger 104 may be equipped with end plates. The Peltier element or heating and/or cooling unit 126 may have a flat surface to connect and is close to the air that shall be heated and/or cooled. The gas channels 106 guide the air in one direction. The enclosure of the heat exchanger 104 may be dimensioned to provide a sufficiently good heat transfer from metal block to air. After having passed the gas channels 106, the air is guided in the opposite direction for closing the circulation. This is the area where sample separation units 30, such as HP LC columns, may be located. Added structures or mounting provisions 112, 116 on the front side 124 allow the sample separation units 30, the preheater assemblies 114, and optionally other elements to be fixed.

[0096] It should be noted that the term "comprising" does not exclude other elements or features and the "a" or "an" does not exclude a plurality. Also elements described in association with different embodiments may be combined. It should also be noted that reference signs in the claims shall not be construed as limiting the scope of the claims.

-28 -AThr

Claims (20)

1. CLAIMS1. A temperature control chamber (100) for controlling temperature of a sample separation unit (30) of a sample separation apparatus (10) for separating a fluidic sample in a mobile phase by the sample separation unit (30), wherein the temperature control chamber (100) comprises a heat exchanger (104) comprising a thermally conductive material and having at least one gas channel (106), preferably a plurality of gas channels (106), through which gas is guidable.
2. 2. The temperature control chamber (100) according to claim 1, wherein the one or more gas channels (106) extend between an open inlet, in particular an open bottom (108), and an open outlet, in particular an open top (110), of the heat exchanger (104).
3. 3. The temperature control chamber (100) according to claim 1 or 2, wherein the one or more gas channels (106) extend in parallel to each other.
4. 4. The temperature control chamber (100) according to any of claims 1 to 3, configured so that said gas is circulated in the temperature control chamber (100).
5. 5. The temperature control chamber (100) according to any of claims 1 to 4, wherein the heat exchanger (104) comprises at least one preheater assembly mounting provision (112), in particular at least one substantially V-shaped recess, for mounting at least one preheater assembly (114) for being directly thermally coupled with the heat exchanger (104), in particular dominated by heat conduction.
6. 6. The temperature control chamber (100) according to any of claims 1 to 5, wherein the heat exchanger (104) comprises at least one sample separation unit mounting provision (116), in particular at least one dovetail connector, for mounting at least one sample separation unit (30) for being indirectly thermally coupled with the heat exchanger (104), in particular dominated by at least one of heat radiation and heat convection.
7. 7. The temperature control chamber (100) according to any of claims 1 to 6, comprising a preheater assembly (114) being directly thermally coupled, in particular being in direct physical contact, with the heat exchanger (104) and configured for preheating the fluidic sample and/or the mobile phase before reaching the sample -29 -separation unit (30).
8. 8. The temperature control chamber (100) according to any of claims 1 to 7, configured for mounting the sample separation unit (30) for being indirectly thermally coupled with the heat exchanger (104), in particular for being decoupled from the heat exchanger (104) concerning heat conduction.
9. 9. The temperature control chamber (100) according to any of claims 1 to 8, comprising a shielding structure (115) delimiting a flow protected space (118) within which the sample separation unit (30) is to be arranged and being configured so that circulating gas flows around but not inside the shielding structure (115).
10. 10. The temperature control chamber (100) according to any of claims 1 to 9, wherein the heat exchanger (104) comprises a back wall (120), side walls (122) and an open front side (124) accessible and configured for accommodating at least one sample separation unit (30) and/or at least one preheater assembly (114).
11. 11. The temperature control chamber (100) according to any of claims 1 to 10, comprising a heating and/or cooling unit (126) thermally coupled with the heat exchanger (104) and being configured for heating and/or cooling the heat exchanger (104).
12. 12. The temperature control chamber (100) according to claims 10 and 11, wherein the heating and/or cooling unit (126) is attached to the back wall (120), in particular to a flat back wall, of the heat exchanger (104), in particular at a vertical position of the back wall (120) corresponding to a lower end of at least one sample separation unit (30) mounted at the heat exchanger (104).
13. 13. The temperature control chamber (100) according to claim 11 or 12, wherein the heating and/or cooling unit (126) is a flat member, in particular a Peltier element.
14. 14. The temperature control chamber (100) according to any of claims 1 to 13, comprising a ventilator (128) for ventilating gas to promote a gas flow into the one or more gas channels (106).
15. 15. The temperature control chamber (100) according to any of claims 1 to 14, -30 -comprising an exterior casing (130) accommodating the heat exchanger (104) so that gas circulates within the casing (130) along a closed circulation path (132) which includes the one or more gas channels (106), and which in particular excludes the sample separation unit (30).
16. 16. The temperature control chamber (100) according to any of claims 1 to 15, comprising at least one of the following features: wherein the heat exchanger (104) is configured as a hollow metal body; wherein the heat exchanger (104) consists of the thermally conductive material, in particular a metal, more particularly aluminum; wherein the heat exchanger (104) comprises or consists of an extruded body; wherein at least a central section of the heat exchanger (104) between opposing open ends (108, 110) of the gas channels (106) has a constant cross-sectional shape along an extension of the gas channels (106); wherein a cross-section of at least part of the gas channels (106) has a hexagonal shape, in particular a honeycomb shape.
17. 17. A sample separation apparatus (10) for separating a fluidic sample, the sample separation apparatus (10) comprising: a fluid drive unit (20) configured for driving a mobile phase and the fluidic sample injected in the mobile phase; a sample separation unit (30) configured for separating the fluidic sample in the mobile phase; and a temperature control chamber (100) according to any of claims 1 to 16 accommodating the sample separation unit (30) for controlling temperature of the sample separation unit (30).
18. 18. The sample separation apparatus (10) according to claim 17, further comprising at least one of the following features: -31 -the sample separation apparatus (10) is configured as a chromatography sample separation apparatus, in particular a liquid chromatography sample separation apparatus, a gas chromatography sample separation apparatus or a supercritical fluid chromatography sample separation apparatus; the sample separation unit (30) is a chromatographic separation column; comprising an injector (40) configured to inject the fluidic sample into the mobile phase; comprising a detector (50) configured to detect the separated fluidic sample; comprising a fractioner unit (60) configured to collect the separated fluidic 10 sample; comprising a degassing apparatus (27) for degassing at least part of the mobile phase; comprising a control unit (70) configured to control operation of the sample separation apparatus (10).
19. 19. A method of controlling temperature of a sample separation unit (30) of a sample separation apparatus (10) for separating a fluidic sample in a mobile phase by the sample separation unit (30), wherein the method comprises: mounting the sample separation unit (30) in a temperature control chamber (100) which comprises a heat exchanger (104) comprising a thermally conductive material and having at least one gas channel (106), preferably a plurality of gas channels (106); and guiding gas through the one or more gas channels (106).
20. 20. The method according to claim 19, wherein the method comprises arranging the sample separation unit (30) in a flow still volume of the temperature control chamber 25 (100).-32 -