EP2044427A1

EP2044427A1 - Equlibrating a temperature profile in a column

Info

Publication number: EP2044427A1
Application number: EP06829911A
Authority: EP
Inventors: Thomas Doerr
Original assignee: Agilent Technologies Inc
Current assignee: Agilent Technologies Inc
Priority date: 2006-07-17
Filing date: 2006-07-17
Publication date: 2009-04-08
Also published as: WO2008009310A1

Abstract

A temperature compensation unit (216) for a fluidic device (200) for analyzing a fluidic sample, wherein the fluidic device (200) is adapted to conduct the fluidic sample along a first direction (215) in the fluidic device (200), the temperature compensation unit (216) being adapted to at least partially compensate a temperature profile in the fluidic device (200) along a second direction (217) which differs from the first direction (215).

Description

DESCRIPTION

EQULIBRATING A TEMPERATURE PROFILE IN A COLUMN

BACKGROUND ART

[0001] The present invention relates to a fluidic device for analyzing a fluidic sample.

[0002] In liquid chromatography, a fluidic analyte (e.g. a mobile phase comprising a sample to be analyzed in a solvent) may be pumped through a stationary phase (e.g. a column) comprising a material which is capable of separating different components of the fluidic analyte. Such a material, so-called beads which may comprise silica gel, may be filled into a column tube which may be connected to other elements (like a control unit, containers including sample and/or buffers) using fitting elements.

[0003] US 5,908,552 discloses a column for capillary chromatographic separations, for example high performance liquid chromatography, including a column bed of packing material arranged in the inner bore of a column.

[0004] US 5,858,241 discloses another column for capillary chromatographic separations.

[0005] US 2004/0156753 A1 by the same applicant, Agilent Technologies, discloses a polyacryl-ether-ketone based microfluidic device comprising two separate substrates which are bonded together to form channels where gases or liquids may move to accomplish applications of the microfluidic device. Thus, an internal cavity may be formed as a lumen or a channel of the microfluidic device.

[0006] During operation, a flow of sample traverses the column tube filled with the fluid separating material, and due to the physical interaction between the fluid separating material and the different components in the fluidic analyte, a separation of the different components of the analyte may be achieved. Consequently, the fluid separating material filled in the column tube may be subject of a mechanical force generated by the fluidic analyte pumped from an upstream connection of the column to a downstream connection of the column with a relatively high pressure. Due to effects like friction, it may happen that a temperature profile is generated in the beads themselves and/or in the fluid being pumped through the separating material. Such a temperature profile may be formed in a direction perpendicular and in a direction parallel to the flowing direction of the sample and may have an impact on the performance of such a liquid chromatography device.

[0007] The dissertation of Gerhard Mayr (1999), University of UIm, Germany, "Bildung und Kompensation von Temperaturgradienten in der schnellen HPLC unter Verwendung von Mikropartikel-gepackten HPLC-Saulen" (available via http://vts.uni- ulm.de/docs/1999/313/vts 313.pdf) discloses the formation and compensation of temperature gradients in a fast HPLC using microparticle packed HPLC columns.

[0008] Jeffrey R. Mazzeo, Uwe D. Neue, Marianna KeIe, Robert S. Plumb, "A new separation technique takes advantage of sub-2-μm porous particles", Analytical Chemistry 467 A, December 2005 (available via httpj/7|3ub^^^_^ discloses that a radial thermal gradient may occur in a chromatography column, and that it is necessary to reduce the column diameter significantly to compensate for such thermal effect in columns packed with small particles.

DISCLOSURE

[0009] It is an object of the invention to enable a proper performance of a fluidic device. The object is solved by the independent claims. Further embodiments are shown by the dependent claims.

[0010] According to an exemplary embodiment of the invention, a temperature compensation unit (which may also be a temperature control unit, for instance for adjusting a temperature for balancing a temperature distribution within the fluidic device) for a fluidic device for analyzing a fluidic sample is provided, wherein the fluidic device is adapted to conduct the fluidic sample along a first direction (for instance a flowing direction) in the fluidic device, the temperature compensation unit being adapted to at least partially compensate a temperature profile in the fluidic device along a second direction (for instance perpendicular to the flowing direction) which differs from the first direction (however, also in the flowing direction, a temperature gradient may be balanced out using a heat control).

[0011] According to another exemplary embodiment, a column (for instance a chromatographic column) for a fluidic device for analyzing a fluidic sample is provided, wherein the fluidic device is adapted to conduct the fluidic sample along a first direction in the fluidic device, the column comprising a column tube and a temperature compensation unit having the above mentioned features for at least partially compensating a temperature profile in the fluidic device along a second direction which differs from the first direction.

[0012] According to still another exemplary embodiment, a fluidic device (for instance a microfluidic device, for example a liquid chromatography apparatus) for analyzing a fluidic sample is provided, wherein the fluidic device is adapted to conduct the fluidic sample along a first direction in the fluidic device, the fluidic device comprising a temperature compensation unit having the above mentioned features for at least partially compensating a temperature profile in the fluidic device along a second direction which differs from the first direction.

[0013] According to yet another exemplary embodiment, a method of treating a fluidic sample is provided, the method comprising forcing the fluidic sample to flow along a first direction, and at least partially compensating a temperature profile of the fluidic sample along a second direction which differs from the first direction.

[0014] According to an exemplary embodiment, a temperature distribution in a cross-sectional area of a column, for instance for liquid chromatography applications, in a direction perpendicular to the flowing direction of a fluidic sample, may be equilibrated actively and artificially by selectively supplying or removing thermal energy in a spatially dependent way.

[0015] When a fluidic sample to be analyzed is pumped (for instance with a pressure of up to 2000 bar or more, or more generally with a pressure in which the fluid may become compressible) through a column of a HPLC (High Performance Liquid Chromatography), an interaction between a moving component (mobile phase, namely the fluidic sample) and a static component (stationary phase, for instance fluid separation material in the form of beads filled in the column) may occur. Due to this interaction and due to an interaction between walls of a column tube and the streaming fluid, a temperature distribution occurs in a radial direction of a tubular column. Friction and other effects are described (for instance in Lauer, Sandra, "Influence of frictional heating on temperature gradients in ultra-high-pressure liquid chromatography on 2.1 mm I. D. columns", Journal of Chromatography) to be the origin of such a temperature distribution. This may particularly have the consequence that fluidic sample flowing along a central or inner part of the column tube may have a larger velocity and temperature than fluid flowing closer to the inner walls of the column tube, that is to say in an outer portion of the cross-sectional area. As can be taken from a van Deemter plot, a temperature distribution along the cross-sectional area of the column may have the consequence that the fluid separation performance differs along the cross-sectional area and may be deteriorated in total. Thus, fractions or bands of components included in the fluidic sample to be separated may smear out, overlap, or may be broadened. Consequently, such a temperature distribution may deteriorate the fluid separation performance of a liquid chromatography apparatus.

[0016] According to an exemplary embodiment, such a performance deteriorating temperature profile in a radial direction of a column tube may be at least partially compensated by selectively modifying the thermal energy distribution along the cross- section. This may be achieved, for instance, by selectively heating outer portions of the cross-section and/or by selectively cooling inner portions of the cross-section. However, since the performance of a liquid chromatography apparatus may improve with increasing temperature, the selective supply of thermal energy to outer portions may be preferred over the selective removal of thermal energy from an inner portion of the cross-section.

[0017] By controlling the temperature distribution over a cross sectional area of a streaming medium (that is particularly an area in a column perpendicular to the flowing direction), the performance of a HPLC may be significantly improved since temperature differences may be at least particularly equilibrated. This may result in narrower bands of fractions of a fluidic sample to be separated along the column which is the direction of the separation, thus improving accuracy, resolution, stability and reproducibility of retention times of the fluid separation. [0018] However, exemplary embodiments are not restricted to liquid chromatography apparatuses, since temperature profiles may also have undesired effects in other fields of fluidic devices, for instance in gel electrophoresis. Also in this technical field, a (e.g. radial) temperature profile essentially perpendicular to the transportation directions in a fluid path may have an impact on the mobility and/or thermally driven properties of components of an analyte, so that also in this technical field an equilibration of a temperature profile may be advantageous.

[0019] According to an exemplary embodiment, a temperature profile resulting from interactions between packing material for a column, walls of the column and fluidic sample to be pumped through the columns may be partially or fully compensated. This may be performed in the context of a high performance liquid chromatography apparatus (HPLC apparatus).

[0020] A column may be used for separating different components of an analyte in a qualitative and/or quantitative manner, in order to identify components of a fluid. A packing material may separate the different components of the fluid/analyte based on different affinities of the individual substances with respect to the column material. Therefore, the analyte may be pumped (with a relative high pressure of some hundred and up to several thousand bar) through the packing material for separation. The high pressure may further increase the problem with large temperature profiles along the radial direction of the column tube.

[0021] As beads, porous silica (silicon dioxide) may be used, for instance with a particle size of 3 μm to 10 μm. Silica Gels may be used which may be baked under a high temperature to form porous spherical clusters. A dimension of a cluster may be 1.8 μm with a component size of 0.01 μm. Such a particle material may have an inner surface of the beads per mass unit of, for instance, 150 m²/g to 300 m²/g. The smaller the particle sizes, the stronger the interactions and therefore the friction between the beads and the fluidic sample, thus intensifying the temperature profile to be equilibrated according to an exemplary embodiment. Temperature control may be particularly advantageous at relatively large cross-sectional areas of the column, like 1.0 mm, 2.0 mm, 3.5 mm, or 4.6 mm.

[0022] The packing material may comprise glass, polymeric powder, silicon dioxide, and silica glass. 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 fractions of the packing material and the analyte.

[0023] As an alternative to a conventional column packing material, planar silica microstructures and/or nanostructures may be used as a separation material. Such materials may be chemically modified to thereby adjust the separation/affinity properties. Such a technology may be an alternative to or a special embodiment of column technology. In this regard, a feature may be the control of the fluidic path length at each position of the separation . Also with such kind of devices, a temperature compensation particular between an inlet and an outlet may be advantageous. Such a temperature compensation unit (like a heating unit) should have a low or zero contribution to the dispersion volume. Thus, such planar structures may be implemented in exemplary embodiments. Such ordered pillared structures have been studied by Fred Reginer or Peter Schoenmakers. Such structures may give an increase in the order of the packing and by controlling the interstitial spacing of the columns may also give a required porosity. With such materials, a temperature management (uniformity especially in a radial direction, but possibly also in a longitudinal direction) may then define the performance. By compensation the temperature between inlet and outlet, an intelligent energy insertion may be achieved. The term "column" may particularly cover fluidic devices having conventional beads as fluid separation material, but also solutions comprising planar silica microstructures and/or nanostructures, or similar materials as separation material.

[0024] According to an exemplary embodiment, control of a radial (and, if desired, optionally of a longitudinal) temperature gradient within a packed particle bed of a

HPLC column may be provided. Such a procedure may allow to resolve the supposed basic contradiction that friction heating within a packed bed of particles as occurring in pressure driven chromatography is lowering the viscosity in the column center thereby increasing the relative linear velocity in the center and at the same time having lower velocity and higher viscosity along the inner wall of the column enhanced by a heat transfer in any desired direction (from an exterior side to an interior side, or vice versa) through the column tube wall itself. The result of this may be peak shape degradation/broadening, , reduced chromatographical resolution and unstable and unreproducible retention time caused parallel fluid streams under different thermal conditions and in different parts of the bed. Especially the heat transient is a critical factor. By the thermal resistance of the column wall itself this leads to the challenge that, by indirect und unspecific heat control through the column wall, no real in-situ control of the radial temperature distribution within the packed particle bed is possible. According to an exemplary embodiment, a way to get rid of this basic constraint is to apply heat directly within the packed bed itself in a spatially dependent manner, favorable in a contactless way, so that the heat transfer and generation is part of the packed particle bed. For instance, this might be done by electromagnetic energy coupling as typically used in any power transformer application.

[0025] An obtainable benefit may be an improved radial heat distribution control which allows to work far beyond present high speed limitations therefore reaching new horizons of productivity and high speed analysis. This can already be applicable and relevant starting from interior diameters of 1 mm (or less) to larger dimensions. An additional optional better control of the longitudinal temperature gradient may help to have generally lower viscosity delivering lower back pressure and therefore again higher achievable linear flow velocity and higher speed at higher resolution.

[0026] An example for achieving that goal might be to wind a wire around the column tube (made of a non-metallic material like ceramics) as a primary inductance and to insert a spring-like secondary inductance (for instance any conductor, appropriate material, for instance, stainless steel) into the column tube which may be short-circuited to serve as a heating element and optionally guaranteeing wall touching by radial spring force. An embodiment is targeted to prevent and/or control inherent energy loss across the column wall, to smooth the radial gradient from center to wall and to further use columns with relatively large interior dimensions with all related advantages like method compatibility or minimal changes thereof.

[0027] According to an exemplary embodiment, it may be possible to control the temperature gradient along a radial direction of a column, thereby having the possibility to obtain a flat radial temperature gradient. Additionally, better longitudinal temperature gradient control may be made possible. [0028] Therefore, any technical measure may be taken having a temperature control effect in an interior of the column for reducing a radial temperature gradient. A control of a temperature gradient in a column in a direction differing from the flowing direction of the fluidic sample may be made possible.

[0029] One goal is to flatten the radial temperature gradient which is believed to be caused by interior friction within the bed of the packed liquid chromatography column. This effect may become particularly relevant with a particle size of less than 2 μm, an inner column diameter (ID) of 2 mm or higher, and generally also with increased pressure and very high flowing rates.

[0030] There are many possibilities of adjusting such a temperature profile. The temperature profile may be controlled in a contactless manner, or in a contact-bound manner. The term "contactless" may particularly denote that the provision of thermal energy may be performed without a (direct) mechanical contact between such an energy delivering unit and the material filled within the interior of the column. An example for a contactless method is an inductive or capacitive coupling from an exterior of the column into an interior of the column so as to deposit energy within an interior of the column. The term "contact-bound" may particularly denote that the temperature is supplied or removed with a direct thermal contact (like a mechanical connection) allowing a thermal equilibration between the material filled in the column tube and the unit for supplying/removing the energy. An example for a contact-bound method is a heating wire supplied within the column for a direct thermal contact with the material to be heated.

[0031] Exemplary solutions are providing or removing heat by convection procedures or by directly heating from an exterior of the column. It is possible to heat the fluidic sample and/or the fluid separation material and/or to heat particles (for instance metal colloids) which may be selectively inserted into the column bed to support contactless heating particularly by (for instance resonantly) absorbing electromagnetic waves.

[0032] With respect to the technical setup of such columns, sufficiently thin steel or ceramic tubes may enable a punctual supply of energy to the critical column inner wall in order to generate a flat radial temperature gradient which, in combination with the natural temperature gradient in an interior of the column, may result in an uniformly temperature controlled cross-section of the tube.

[0033] According to one embodiment, a limited penetration depth of energy (for instance in the form of electromagnetic waves) into the column bed may be used (for instance infrared absorption, high-frequency absorption and/or interaction with polar solvents, for instance water, dipole-dipole interactions, Van der Waals interactions, etc.). Such effects may be used particularly for the contactless energy transfer e.g. through the glass, ceramic and/or metal tube. Here the physical interaction may have impact on areas around the overheated core first which is another methodology to compensate for flat radial temperature profiles.

[0034] According to another exemplary embodiment, any suitable impurities may be selectively inserted (for instance with a statistical distribution) into the column bed which, by contactless energy transfer, may manipulate the temperature profile in a desired manner. Appropriate shapes of impurities are powder materials, granulates, spiral springs, rods or a heating tube within the column tube (for instance a heated intermediate wall).

[0035] Not only a temperature profile along a radial direction of the tube may occur, but also in a longitudinal flowing direction of the fluidic sample. A "longitudinal gradient" may have the consequence that the separation at the end of the column may be faster as compared to the separation at the beginning of the column. When the column is tempered in an undesired manner (for instance equal temperature), the column wall may be colder as compared to the core at a portion close to the end of the column, which may smear out the fractions to be separated. This negative influence on the performance of the fluidic device may be compensated as well at least partially, by varying the energy transfer along the longitudinal direction of the column.

[0036] Thereby, by compensating a temperature profile along a cross-section and/or along a longitudinal direction of the column tube, the local temperature distribution within the tube may be equilibrated so that disturbing effects like a superposition of peaks related to different fractions of the sample may be avoided or at least suppressed. [0037] In order to compensate a positive temperature profile in a radial direction (that is a high temperature in a center and a lower temperature in an outer portion of the column tube), a negative temperature profile (that is supplying less thermal energy to or removing more thermal energy from the center and supplying more thermal energy to or removing less thermal energy from the outer portion of the column tube) may be impressed. In other words, the present temperature profile and the superimposed temperature profile may be complementary. This may allow for a temperature management within the column, by selectively heating or cooling in a spatially dependent manner along a radial direction within the column tube, thereby flattening a radial temperature profile.

[0038] According to an exemplary embodiment, a programmable and essentially delay-free temperature gradient may be generated by an active control of the thermal heat distribution in a column tube ("zero" dispersion heating). It may be made possible according to exemplary embodiments to obtain an essentially immediate temperature modification in contrast to a very long time for a heat equilibration. Exemplary embodiments may be implemented in the context of HTLC (High Temperature Liquid Chromatography, that is an LC apparatus operating at temperatures larger or significantly larger than 60⁰C, up to 200⁰C and more) and "green" chemistry. At high temperatures, the polarity of the solvent may be modified such that it may be possible to carry out separations using water, which separations are otherwise only possible with organic solvents. In other words, separations can be carried out dynamically not only using different solvents of different polarity, but also with different temperature during an analysis.

[0039] It is also possible to define a desired time-dependency of a temperature distribution (or a homogeneous temperature value) which is desired in the column, for example during a user-specific experiment to be carried out. The temperature control unit may then control the column internal temperature so that the desired time- dependency of the temperature distribution is made possible. For this purpose, the fluidic device may comprise a user interface to allow such a user-defined temperature control.

[0040] According to an exemplary embodiment, an essentially dead volume free heating and/or an essentially delay-free heating may be made possible when using the column input frits as heating elements themselves by contactless (e.g. inductive heating) or contact heating (applying a current across a very low ohmic frit resistance) . Those frits may be mandatory parts of each column to hold back the packing material while being adjusted or optimized for reduced or minimum band spreading. A typical approach is to use a sintered stainless steel metal dust with a controlled pore size.

[0041] According to an exemplary embodiment, it is possible to combine a high performance with high pressures and flow through volumes. As a fluid separation material, silica gel beads or polymers may be used, for instance with dimensions between 5 μm and 3.5 μm. So-called "sub-two-μm" beads having a dimension of less than 2 μm may allow to obtain an even better separation performance and a better dispersion characteristic. The described fluid separation materials may be appropriate even for very high temperature applications.

[0042] Embodiments of the invention may be implemented in the context of liquid chromatography apparatus, particularly of a High Performance Liquid Chromatography (HPLC). For fluid separation, the fluidic sample is pumped through the arrangement with a high pressure (of larger than 200 bar, up to 1000 bar and more). A separation may occur in accordance with a chemical interaction between beads and the components of the fluidic sample (in accordance with affinities). Therefore, different retention times for the different fractions may result in a separation. The separated fractions may then be detected (e.g. read out), preferably optically (for instance using physical parameters like absorption or fluorescence properties) or using a mass spectroscopy device.

[0043] The smaller the particles in an LC column, the larger is the resistance of the column with respect to fluidic sample. The smaller the beads and the larger the pressure, this interaction increases. With a so-called "rapid resolution LC", a high resolution per time may be obtained.

[0044] As beads, silica gel with baked 10 nm particles may be used, so that beads in an order of magnitude or 1.8 μm, 3.5 μm, 5 μm, or 10 μm may be generated. It is also possible to attach functional groups to the beads so as to promote a desired affinity. [0045] With respect to the fluid separation techniques, particularly two aspects may be distinguished. A preparative separation may be implemented for a purification of a sample. An analytic separation may be used for detection which components are present in an unknown sample under examination.

[0046] As can be taken from a van Deemter diagram as shown in Fig. 1 and which will be described below in more detail, a small bead particle size may increase the performance of an LC apparatus, wherein an optimum velocity value increases. Beyond this, the van Deemter curves are temperature dependent, wherein again a further improved or optimum velocity value increases the fluid separation performance therefore allowing higher speed analysis with same resolution in general. High temperature (gradients) within the column instead will result in bad peak shape and low resolution by facts described already above. As indicated by the van Deemter plot, small particles result in a flat curve, large temperatures result in a flat curve, and especially a radial temperature profile may result in a broadening of the peaks. Such a radial temperature profile may deteriorate the performance of an LC.

[0047] By reducing the temperature gradient by supplying or removing energy in a spatially dependent manner from the efficient column cross-section, a high degree of flexibility and a high level of performance may be obtained.

[0048] Such a radial temperature gradient and/or a longitudinal temperature gradient may result from friction between column wall and fluidic sample. This generates a velocity profile. This velocity profile results in a temperature profile by friction between the fluidic sample and the beads/the solvent.

[0049] The radial temperature compensation may be obtained by heating an interior wall of the column tube. For applying a longitudinal temperature profile, this may have a stepless or stepwise temperature adjustment.

[0050] As exemplary appropriate column tube wall materials, stainless steel, ceramics, quartz, glass or other appropriate materials may be used. The wall thickness can be few millimeters to obtain both a high degree of mechanical stability and the possibility to efficiently introduce heat into the system. [0051] For adjusting the way of heating, benefit can be taken of the properties of the solvent, the fluid separation material, the fluidic sample, and the wall material of the column. The wall, for instance, may be used as an active heating element. Alternatively, ultrasonic sound, microwaves, high-frequency radiation, an inductive coupling of energy, etc. may be used. For instance, an annular microwave emitter may be attached at an outside of the column tube. When the wall of the column tube is manufactured from a microwave transmitting material, the microwaves are absorbed by the fluidic sample, wherein a penetration depth of the system for microwaves may be taken into account. When using infrared radiation, the infrared absorption properties of fluid separation material and/or solvent and/or fluidic device may be used, wherein resonance effects may be used advantageously.

[0052] It is also possible to provide an ohmic heating attached to and/or integrated in the wall of the column. An inductive or capacitive coupling may also be implemented for thermal power supply. For this purpose, a primary and a secondary transformator coil may be used for introducing heat in a contactless manner into an interior of the column tube. When using induction for supplying thermal energy, metal rings may be heated integrated in or attached to an interior wall of the column tube. Spiral springs which may be short circuited and which may be, optionally, foreseen with a gradient of the winding number per length along the longitudinal axis of the column tube, may be provided. Short circuiting a secondary winding, the electric energy can be transformed into thermal energy, for selectively heating outer portions of the fluid stream.

[0053] It is also possible to position a rod (or the like) centrally within the column, wherein such a central rod may serve as a heat sink for guiding or for leading off thermal energy from the hot core of the fluidic sample stream to an outside of the column, like to a heat consumer or a cold reservoir. The rod may be warmed by being brought in contact with column beads and/or a mobile phase for a sufficiently long time. An actively remove of heat may be possible as well. Providing a rod in a central portion may reduce the distance between centrally located beads and beads located close to the wall of the column tube, which may suppress the generation of an intensive radial temperature gradient, in a similar manner as in small column tubes having an inner diameter of less than, for instance, 2 mm. The rod can also be used for an active heating. [0054] It is also possible to provide pure mechanical elements within the column tube so as to generate a hydrofluidic stream for splitting up different fluid stream fractions, or for mixing up different fluid stream fractions so as to obtain a mechanically induced equilibration of temperature.

[0055] Therefore, a thermal manipulation and/or a mechanical manipulation of the fluidic sample may be performed so as to compensate the temperature profile.

[0056] Optionally, the temperature control unit may be arranged to adjust a temperature of the fluidic sample in a flow path between an inlet of the column and an outlet of the column so that a temperature adjustment effect occurs selectively and only in an interior of the column, so that the temperature adjustment effect does not occur before the fluidic sample enters the inlet of the column. This may allow to reduce the amount of energy transfer and may allow to control temperature related properties in a spatially accurate manner.

[0057] Next, further exemplary embodiments will be explained. In the following, further exemplary embodiments of the temperature control unit will be explained. However, these embodiments also apply for the column, for the fluidic device and for the method.

[0058] The temperature control unit may be adapted to at least partially compensate a temperature profile in the fluidic device originating from friction between the fluidic sample flowing in the fluidic device and a stationary packing material filled in the fluidic device. Based upon representative locations for temperature feedback, the temperature profile may be modeled, and the external compensation profile may be adjusted so as to compensate this interior profile as good as possible.

[0059] The first direction may be essentially perpendicular to the second direction. Therefore, a heat profile in a transversal direction with respect to a longitudinal fluid flow direction may be counterbalanced.

[0060] The fluidic device may comprise a tube and may be adapted to conduct the fluidic sample along a longitudinal direction of the tube. The temperature control unit may further be adapted to at least partially compensate the temperature profile in the fluidic device along a radial direction of the tube. Therefore, exemplary embodiments may be implemented in circularly shaped tubes, wherein this symmetric geometry may allow for a symmetric and therefore easy compensation.

[0061] The second direction may be part of a plane being aligned essentially perpendicular to the first direction. The temperature control unit may be adapted to at least partially compensate the temperature profile within this plane. The fluidic sample fractions pass subsequent planes which are arranged along the flowing direction of the fluidic sample. For each of these thin (virtual) planes or thin disks, the temperature adjustment may be performed individually such that along the radial direction, and optionally also along the longitudinal direction, a desired temperature profile may be averaged. This may result in (more) homogeneous temperature properties over the entire tube.

[0062] The temperature control unit may comprise a thermal energy source for selectively supplying thermal energy to relatively cold components (that is to say components of the fluidic sample which have a lower temperature than other, relatively hot, components of the fluidic samples) of the fluidic sample. As already described, along the cross-section of the fluidic sample, a core is usually hotter than surrounding rings. Therefore, the relative cold components at an exterior portion with respect to components in a central portion of the interior of the tube may be selectively heated.

[0063] Such a thermal energy source may be adapted for applying a temperature profile between an inner portion of the fluidic sample within the fluidic device and an outer portion of the fluidic sample within the fluidic device by supplying more thermal energy to the outer portion than to the inner portion. This procedure takes into account that, due to friction effects between wall and fluidic sample, the inner portions of such a for instance cylindrical fluidic sample are colder than the inner portions.

[0064] The temperature control unit may comprise a mechanical barrier designed and positioned for selectively redirecting or mixing different components of the fluidic sample at least partially along the second direction to thereby modify a flowing profile of the components to at least partially compensate the temperature profile. In other words, different portions of the fluid stream may be directed to different portions along the cross-sectional area of the column. Therefore, relatively hot components may be directed into relatively cold components so as to compensate the temperature profile by such a redirection or mixing.

[0065] The temperature control unit may be adapted to at least partially compensate the temperature profile using at least one mechanism of the group consisting of heat conduction, heat convection, and heat radiation. The term "heat conduction" may be denoted as the transmission of heat across a material, via a continuous mechanical path. The term "heat convection" may be denoted as the transfer of heat by currents within a fluid (wherein the term fluid may here denote a gas and/or a liquid). It may arise from temperature differences within the fluid or between the fluid and its boundary. The term "heat radiation" may be denoted as the only form of heat transfer that can occur in the absence of any form of medium and as such is the only way of heat transfer through a vacuum. Thermal radiation may be a direct result of the emission of electromagnetic radiation, which carries energy away from the surface. Furthermore, when a surface is bombarded by electromagnetic radiation from the surroundings, this may also result in the transfer of energy to the surface.

[0066] The temperature control unit may further be adapted to at least partially compensate a temperature profile in the fluidic device along the first direction. In addition to the radial equilibration, also a temperature gradient along the streaming direction of the fluidic sample may be at least partially compensated. For instance, the heat transfer may be controlled according to a predetermined spatially dependent function so as to selectively provide more or less thermal energy to different portions or sections along the longitudinal extension of the column. For instance, a linearly increasing temperature profile may be applied along the extension of the tube, wherein the linear function of the longitudinally applied heat may increase along the flowing direction of the fluidic sample.

[0067] The temperature control unit may further comprise a thermal energy sink for selectively absorbing thermal energy from relatively hot components (that is to say components of the fluidic sample which have a higher temperature than other, relatively cold, components of the fluidic samples) of the fluidic sample. In a scenario, in which it shall be avoided that the entire column or a part thereof is additionally heated by the temperature equilibration procedure, thermal energy can be removed selectively from such portions of the column tube which shall be cooled or prevented from being further heated.

[0068] In the following, further exemplary embodiments of the column will be explained. However, these embodiments also apply for the temperature control unit, for the fluidic device and for the method.

[0069] The temperature control unit of the column may comprise a thermal energy source for providing thermal energy to components of the fluidic sample in dependence of a distance of a component from a center of the column tube. Therefore, any desired mathematical function can be defined for compensating the temperature profile. For instance, the temperature deposition may be designed to have a linearly increasing spatial dependence from a radius r=0 to r=R (R being the inner radius of the tube).

[0070] The thermal energy source may comprise a heating wire wound in at least one manner of the group consisting of being wound along an inner surface of the column tube, being wound along an outer surface of the column tube, and being accommodated in an interior of the column tube. An AC current or a DC current may be applied to the heating wire. The heating wire may have a spiral shape or may also have the shape of a hollow cylinder lined along an inner surface of the tube. Electric current can be injected into one or a plurality of portions along the extension of the column tube, wherein the latter embodiment allows a more accurate definition of the temperature profile compensation. It is also possible that the heating wire(s) has or have an essentially straight geometry.

[0071 ] The thermal energy source may comprise a heating fluid stream generating element for generating a hot fluid stream to be brought in thermal contact with the column tube. For instance, blowing hot air in defined manner to an outer surface of the column tube may allow to heat the column tube in a defined manner, wherein by heat conduction at least a part of this energy may be transferred into the fluidic sample. It is also possible to provide some kind of hollow cylindrical structure within the column tube through which hollow cylindrical structure a hot air or a hot liquid stream may be passed to be brought in thermal interaction with the fluidic sample so as to equilibrate the temperature profile. [0072] The thermal energy source may also comprise an electromagnetic radiation generation unit for generating electromagnetic radiation. Such electromagnetic radiation may have any desired wavelength, like radio frequency (RF), microwaves, infrared, optical light, ultraviolet light, or X-rays. The absorption characteristics of the different electromagnetic radiation frequency ranges may be taken into account. Furthermore, radioactive sources (like an α-emitter, a β-emitter or a γ-emitter) may be used for heating.

[0073] The thermal energy source may further comprise an ultrasound generation unit for generating ultrasound radiation. The absorption of ultrasound radiation, that is to say mechanical waves, may also heat the sample in a defined manner, so that a desired temperature profile can be adjusted.

[0074] The thermal energy source may comprise a primary inductive coupling element (which may be located outside of the tube) for providing an alternating electrical signal and may comprise a secondary inductive coupling element located attached to or integrated in the column tube and inductively coupled to the primary inductive coupling element. The coupling scheme may be, as an alternative to a pure inductive coupling, be also a pure capacitive coupling or a mixed inductive and capacitive coupling. For instance, a coil may be arranged to surround the column, and within the material of the column or at an outer or inner wall surface of the column, a secondary coil may be provided. The secondary coil may be short-circuited so that inductions currents generated in the secondary coil may be transformed into heat which may then be used to equilibrate the temperature profile.

[0075] This secondary inductive coupling element may comprise one or a plurality of metal rings located at or in the column tube, or a metal coil located at or in the column tube. It is also possible to use, as a secondary inductive element, a thin-walled hollow cylinder of a metallic material. The metal rings located along a longitudinal direction of the column may vary in thickness, length or ohmic resistance so that, by varying these geometry parameters, the heat transfer may be adjusted along an extension of the column.

[0076] The column tube may have an essentially cylindrical bore, wherein the temperature control unit may be adapted for compensating the temperature profile in a radial direction of this bore. Such a bore may have a cylindrical shape (and a circular cross-section) through which the fluidic sample may be pumped.

[0077] The temperature control unit may further comprise a temperature profile generating element for generating a longitudinal temperature profile along the first direction. Therefore, also a combination of a radial and a longitudinal temperature compensation may be made possible, so that the three-dimensional temperature control over the entire filling of the column may be made possible. The longitudinal temperature compensation may be performed as well as an alternative to the radial temperature compensation

[0078] At least a part of the column tube may be filled with a fluid separating material. Such a fluid separating material may be silica gel, carbide, polymers, etc. The fluid separating material may have the effect to separate different fractions of the fluidic sample due to the different affinity between the fluid separating material and the fluidic sample.

[0079] At least a part of the column tube may be filled with a fluid separating material which comprises beads having a size in the range of essentially 0.5 μm to essentially 50 μm. Thus, these beads may be small particles which may be filled inside the column.

[0080] At least a part of the column may be filled with a fluid separating material comprising beads having pores of a size in the range of essentially 0.02 μm to essentially 0.03 μm (porous material) or non-porous material. The fluidic sample may interact by pores and/or modified surfaces of porous or non-porous materials, wherein an interaction may occur between the fluidic sample and the pores. By such effects, separation of the fluid may occur.

[0081] The temperature control unit may comprise a thermal energy sink for absorbing thermal energy from components of the fluidic sample in dependence of a distance of a component from a center of the column tube. As already mentioned above, as an alternative to supplying energy, it is also possible to selectively thermally de-energize parts of the column filling. Such a thermal energy sink may be adapted for absorbing more thermal energy from components of the fluidic sample which are located closer to the center of the column as compared to components of the fluidic sample which are located further away from the center of the column tube. For instance, a thermally conductive wire with a large heat capacity may be provided along the center of the column and may be thermally coupled to a cooling bath located outside of the column, for instance an ice bath. This may selectively absorb energy from the portion of the filling of the column which is hottest, namely the central portion.

[0082] The column tube may comprise at least one of the material group consisting of steel, ceramics, quartz and glass and other materials. The material of the column tube may be adjusted to the specific way of supplying and/or absorbing energy. For instance, when energy shall be supplied from outside, a material with a low thermal resistance may be used.

[0083] In the following, further exemplary embodiments of the fluidic device will be explained. However, these embodiments also apply for the temperature control unit, for the column and for the method.

[0084] The fluidic device may comprise a sensor for measuring the temperature profile in the fluidic device along the second direction. Furthermore, a regulator unit may be provided for regulating the temperature control unit for compensating the temperature profile based on a measurement performed by the sensor. Therefore, a feedback loop may be implemented, in which the actual temperature profile may be measured and, as a result of this measurement, the mode of supplying thermal energy to the system may be increased, reduced, or the spatial dependence of the heat supply may be adjusted or regulated. The measurement of the temperature profile may occur, for instance, using any one or more dimensional (for instance array-like) temperature sensor which may measure the (spatial dependence of the) temperature distribution within the column in a contact-bound or contactless manner, particularly a temperature distribution in the second direction or in a plane containing the second direction.

[0085] The fluidic device may be adapted as a fluid separation system for separating components of the fluidic sample. When a fluidic sample is pumped through the fluidic device, preferably with a high pressure, the interaction between a filling of the column and the fluidic sample may allow for separating different components of the sample, as performed in a liquid chromatography device or a gel electrophoresis device.

[0086] However, the fluidic device may also be adapted as a fluid purification system for purifying the fluidic sample. By spatially separating different fractions of the fluidic sample, a multi-component sample may be purified, for instance a protein solution. When a protein solution has been prepared in a biochemical lab, it may still comprise a plurality of components. If, for instance, only a single protein of this multi- component liquid is desired, the sample may be forced to pass the column. Due to the different interaction of the different protein fractions with the filling of the column (for instance using a gel electrophoresis device or a liquid chromatography device), the different samples may be distinguished, and one sample or band of material may be selectively removed as a purified sample.

[0087] The fluidic device may further be adapted to analyze at least one physical, chemical or biological parameter of at least one component of the fluidic sample. 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.

[0088] The fluidic device may comprise at least one of the group consisting of a sensor device, a test device for testing a device under test or a substance, 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, and a mass spectroscopy device. Particularly, the fluidic device may be a High Performance Liquid Chromatography device (HPLC) in which different fractions of an analyte may be separated, examined and analyzed.

[0089] The fluidic device may be adapted as microfluidic device. The term "microfluidic device" may particularly denote a fluidic device as described herein which allows to convey fluid through micropores, that is pores having a dimension in the order of magnitude of micrometers or less.

[0090] The fluidic device may be adapted to conduct the fluidic sample in the fluidic device with a high pressure, particularly a pressure of more than 100 bar, more particularly of more than 200 bar, for instance with essentially 400 bar, particularly of at least 500 bar or more.

[0091] It is possible to combine the generation of a desired radial temperature profile with the generation of a longitudinal temperature profile. This may allow to control the temperature distribution along both the radial and the longitudinal extension. For instance, the adjustment may be performed in such a manner that, over an entire extension of the column tube, the inner temperature is kept smaller than the outer temperature (self-heating of the fluid is neglected in this consideration, but may be considered as well).

BRIEF DESCRIPTION OF DRAWINGS

[0092] 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.

[0093] Fig. 1 shows a van Deemter plot.

[0094] Fig. 2 and Fig. 3 show fluidic devices comprising temperature control units according to exemplary embodiments of the invention.

[0095] Fig. 4A to Fig. 4C show temperature profiles along an extension of a column tube.

[0096] Fig. 5 to Fig. 11 show temperature control units according to exemplary embodiments.

[0097] The illustration in the drawing is schematically.

[0098] In the following, referring to Fig. 1 , a van Deemter plot 100 will be explained to provide some background information about the effects which are used by exemplary embodiments and to explain recognitions one which exemplary embodiments are based. [0099] The van Deemter diagram 100 in Fig. 1 comprises an abscissa 101 along which the velocity of a fluidic sample to be transported through a column is plotted in mm/s. Along an ordinate 102 of the diagram 100, the so-called plate height H is plotted in μm, which is a measure for the separation performance, that is to say for the efficiency of separating the fluidic sample into different fractions. Thus, a separation performance, efficiency or resolution is plotted along the ordinate 102.

[00100] In a first curve 103, a dependency is shown for beads (as fluid separating material) with a size of 10 μm. A second curve 104 is related to beads with a size of 5 μm, and a third curve 105 is associated to fluid separation particles with a size of 3 μm.

[00101] Furthermore, Fig. 1 shows a fourth curve 106 which is formed by connecting the minima of the curves 103 to 105 (and of other curved for other bead sizes). The curve 106 illustrates a respective optimum operation condition for best resolution per time for the respective particle size.

[00102] The column pressure increases inversely with the particle size square. The velocity at the minimum of the curves 103 to 105 increases with the inverse of the particle size. The column pressure and the minimum of the van Deemter curves 103 to 105 increases with inverse of the cubic power of particle size.

[00103] Fig. 1 indicates a relationship between the linear interstitial velocity plotted along the abscissa 101 and the separation performance plotted along the ordinate 102. However, the van Deemter curves 103 to 105 are also temperature dependent. Therefore, when the temperature varies along a cross-section of an LC tube, the separation performance H plotted along an ordinate 102 changes as well for the different portions with different velocities and temperatures.

[00104] In the light of the foregoing, embodiments of the invention are based on the recognition that different temperatures in different sections of the fluidic device will result in different individual interstitial velocities thereby leading to mixed individual resolution performance with deteriorated overall analytical resolution (the worst parts will dominate the best). It therefore may be advantageous to at least partially compensate a temperature profile along a cross-section of the column tube in an efficient manner to obtain a high separation performance. [00105] In the following, referring to Fig. 2, a fluidic device 200 according to an exemplary embodiment will be explained.

[00106] The fluidic device 200 is adapted as a system for carrying out liquid chromatography investigations. The fluidic device 200 for separating different components of a fluid which can be pumped through the apparatus 200 comprises a column 201 having a column tube 202 which is shaped as a hollow cylinder. Within this cylinder, a tubular reception 203 is defined which is filled with a package composition 204.

[00107] The fluidic device 200 is adapted as a liquid chromatography device comprising a first frit 205 close to an inlet 207 of the column 201 and a second frit 206 provided at an outlet 208 of the column 201. A first fitting element 207 forms the inlet and is provided upstream the column tube 202. A second fitting element 208 forms the outlet and is located downstream of the column tube 202. A flowing direction of fluid which is separated using the fluidic device 200 is denoted with reference numeral 209.

[00108] A fluid separation control unit 210 is provided which pumps fluid under pressure of, for instance, 200 bar through a connection tube 211 and from there through the fitting element 207 and the first frit 205 into the column tube 202. After having left the column tube 202, that is to say after having passed the second frit 206 and the second fitting element 208, a second tube or pipe 212 transports the separated analyte to a container and analysis unit 213. The container and analysis unit 213 includes cavities or containers for receiving different components of the fluid, and may also fulfil computational functions related to the analysis of the separated components.

[00109] The column tube 202 comprises the filling 204. In other words, a packing composition 204 comprising a plurality of silica gel beads 214 is inserted into the hollow bore 203 of the column tube 202.

[00110] The fluidic device 200 is adapted for analyzing a fluidic sample, and is adapted to conduct the fluidic sample along a first direction 215, namely a longitudinal direction of the fluid flow, in the fluidic device 200. [00111] The fluidic device 200 comprises a temperature control unit 216 (which is plotted only schematically in Fig. 2) for at least partially compensating a temperature profile in the fluidic device 200 along a second direction 217 which differs from the first direction 215, or more generally in a plane which is including the second direction 217 and which includes the first direction 215. The temperature control unit 216 is adapted to at least partially compensate the temperature profile in the fluidic device 200 originating from friction between the fluidic sample flowing in the fluidic device 200 and the stationary packing material 214 filled in the fluidic device 200. The first direction

215 is oriented essentially perpendicular to the second direction 217. The fluidic device comprises the tube 202 for conducting the fluidic sample along the longitudinal direction 215 of the tube 202. The temperature control unit 216 compensates the temperature profile in the fluidic device along a radial direction 217 of the tube. The term "radial" direction may particularly denote any direction in a plane perpendicular to the longitudinal direction 215.

[00112] Before a plurality of different embodiments for the temperature control unit

216 will be described in more detail referring to Fig. 5 to Fig. 10, reference is made to the fluidic device 300 shown in Fig. 3.

[00113] Referring to Fig. 3, a microfluidic device 300 according to an exemplary embodiment will be described.

[00114] The microfluidic device 300 comprises a first essentially planar member 301 and a second essentially planar member 302. In an operation state in which the first essentially planar member 301 is coupled to the second essentially planar member 302 (for instance using a glue connection), a column tube is formed by a recess 303 which is formed in the first essentially planar member 301 and by the planar surface of the second essentially planar member 302. The recess 303 forms, when the members 301 and 302 are connected to one another, a channel-like structure which has a similar function like the inner bore 203 of the column tube 202 of Fig. 2.

[00115] The microfluidic device 300 can be used in a similar manner as described in Fig. 6a, 6b and corresponding description of US 2004/0156753 A1.

[00116] Fig. 3 illustrates a patterned PEEK (Polyacryletherketone) substrate 301 having the internal cavity 303 and the other flat surface 302 that can be bonded with the patterned PEEK substrate 301 to form the microfluidic device 300. The flat substrate 302 can be formed by any solvent resistant material, including, but not limited to, PEEK or glass. The patterned PEEK substrate 301 can be formed using any fabrication technique, including embossing, laser ablation, injection moulding, etc. It should be further understood that the microfluidic device 300 can include multiple channels 303, and each channel 303 can include a packing composition with a fluid separation material.

[00117] As shown in Fig. 3, the channel 303 comprises a central portion which may be filled with fluid separating material, like silica beads. Furthermore, a first frit 205 and a second frit 206 are shown. The fluid separating beads may be inserted into a central portion 304 of the recess 303, that is to say in the entire portion of the recess 303 which remains when the frits 205, 206 are inserted in the end portions of the recess 303.

[00118] In order to control a temperature distribution within the channel 303, a secondary induction coil 305 is formed embedded in the first substrate 301 and (although not shown in Fig. 3) correspondingly formed in the second substrate 302. When the first substrate 301 is connected to the second substrate 302, the electrically conducting structures 305 form a common spiral in the interior of which the channel 303 is housed. When an external coil (not shown in Fig. 3) carrying alternating electric current is provided, and when such a primary coil is inductively coupled to the secondary coil 305, induction currents are generated in the (short circuited) secondary coil 305 which are transformed into ohmic heat. This ohmic heat may then influence or modify the temperature of material filled in the channel 303. By taking this measure, a temperature profile of a fluidic sample flowing in the recess 303 may be at least partially equilibrated, in dependence of the externally controlled current source for powering the primary coil. The primary coil and the secondary coil 305 may be considered to form a kind of transformator. The winding distance preferably is adjusted or optimized for compensating the longitudinal heating process which may lead to non- linear distances between the windings.

[00119] In the following, referring to Fig. 4A to Fig 4C, a cross-section of a column tube 202 is shown.

[00120] The second direction 217 is plotted along an ordinate of the corresponding diagrams. Along an abscissa of the diagrams of Fig. 4A to Fig. 4C, the first direction 215 is plotted.

[00121] Furthermore, a flowing direction of a fluid 400 flowing through the column tube 202 is also shown. Close to an inlet portion of the column tube 202 (that is to say referring to Fig. 2 close to the frit 205) a first temperature distribution 410 is obtained which is still relatively homogeneous and which is shown in Fig. 4A. The temperature distribution follows a function 420 which is indicated schematically in Fig. 4B. At an end portion of the column tube 202, that is to say close to the frit 206, a temperature distribution 430 can be observed which is very inhomogeneous and which is shown in Fig. 4C. The described characteristic is obtained because - in addition to an parabolic stream characteristic (the fluid at the core is faster than the fluid close to the wall) - the core is heated due to friction with the packing material in a progressive manner along the column. This may result in an increase of the viscosity, which further increases the core velocity and temperature by further increased friction of solvent and particles. Thus, the characteristic plotted along the axis 215 in Fig. 4A to Fig. 4C does not describe the core velocity but the relative temperature increase (which goes hand in hand with a larger velocity) at the inlet, the middle and the end of the column. The dotted line 440 describes schematically which heat distribution should be added to obtain an equilibrated temperature of the front close to an inlet of the column.

[00122] This velocity distribution 410, 420, 430 may result in a temperature profile along the x-axis of the column tube 202, resulting in a hot core in a central symmetry axis of the cylindrical column tube 202 and in a lower temperature at the border portions, that is close to the walls of the column tube 202.

[00123] Therefore, according to exemplary embodiments, measures may be taken to at least partially compensate this temperature profile so as to have a more homogeneous temperature profile along the second direction 217.

[00124] Fig. 5 to Fig. 11 which will be explained in the following show exemplary embodiments of a temperature control unit capable of balancing the temperature distribution.

[00125] In the embodiment of Fig. 5, a temperature control unit 500 is shown which is adapted as a thermal energy source for selectively supplying thermal energy to material in the interior of the column tube 202.

[00126] The thermal energy source of the temperature control unit 500 of Fig. 5 comprises a primary inductive coupling element 501 , namely a primary coil wound around the outside of the column tube 202 and adapted for providing, using a current source 502, an alternating electrical signal. In other words, an alternating current is generated by the current source 502 and is supplied to the primary coil 501. Furthermore, the temperature control unit 500 comprises a secondary inductive coupling element 503, namely a metal coil embedded in an interior of the column tube 202. When an alternating current is supplied to the primary coil 501 , the transformator principle generates a secondary current in the secondary coil 503 which is converted into ohmic heat. This ohmic heat may be supplied to an interior of the column tube 202 to selectively heat material contained therein.

[00127] A thermal energy reflection element may be provided in the column tube 202 outside of the secondary coil 503 so as to reflect any thermal radiation or the like which propagates towards the outside of the column tube 202. Such radiation may be reflected back to contribute to the heating of an interior of the tube 202. Particularly, portions along an outer diameter of the interior of the column tube 202 are heated predominantly, since the distance between the generation of the heat at the secondary coupling 503 in these outer portions is smaller than a distance between the secondary coil 503 and an interior of the column tube 202 (that is to say a portion located adjacent to a symmetry axis of the column tube 202).

[00128] In the following, referring to Fig. 6, a temperature control unit 600 according to another exemplary embodiment will be explained.

[00129] The temperature control unit 600 comprises a thermal energy sink for selectively absorbing or guiding away thermal energy from relatively hot components of the fluidic sample. [00130] According to the embodiment of Fig. 6, a cooling wire 601 of a material with a large value of the thermal conductivity and with a large value of a heat capacity may be arranged essentially along a central axis of the cylindrical bore of the column tube 202. End portions of the cooling wire 601 are connected to an ice bath 602 located exterior of the column tube 202. The central portion of the fluidic sample passing along the longitudinal direction 215 through the column tube 202 may become particularly hot, as compared to portions of the fluidic sample which are located further away from or remote of the central axis of the bore of the column tube 202. Therefore, a temperature equilibration may be carried out using this thermal energy sink which selectively absorbs energy from a central portion of the cylindrical bore.

[00131] With a geometric configuration similar to Fig. 6, the cooling wire 601 may be substituted by a Peltier element for cooling or heating an interior of the column tube 202 using the Peltier effect.

[00132] Alternatively, it is also possible to cool the mobile phase before entering a warm(er) column tube. The column tube may also be warmed only along a portion thereof, for instance only warmed along the second (in fluid flow direction) longitudinal half of the tube.

[00133] In the following, referring to Fig. 7, an exemplary embodiment of a temperature control unit 700 will be explained.

[00134] The temperature control unit 700 comprises a first heating wire 701 connected to a first direct current (DC) source 702 and comprises a second heating wire 703 connected to a second direct current source 704. Although only two heating wires 701 , 703 as shown in Fig. 7, a plurality of such heating wires may be provided along an outer circumference of the interior of the cylindrical column tube 202. Therefore, thermal energy is supplied along a circumference of the outer diameter of the bore of the column tube 202 so as to selectively heat outer portions of the fluidic sample. As an alternative, only a single heating wire may be provided, or a heating hollow cylinder which may be fed with an electrical current may be provided. The electrical current generates ohmic heat which then is transmitted to the fluidic sample.

[00135] In the following, referring to Fig. 8, a temperature control unit 800 according to an exemplary embodiment will be explained.

[00136] The temperature control unit 800 does not comprise any thermal energy sink or source but comprises a plurality of mechanical barriers 801 provided at different portions of an interior of the column tube 202. These mechanical barriers 801 are designed and positioned for selectively redirecting and/or mixing different portions of the fluidic sample streaming from the left hand side to the right hand side of Fig. 8. By mixing hot and cold portions, a temperature equilibration may be obtained.

[00137] Mechanical temperature control mechanisms can also be combined with energy supply temperature control mechanisms and/or with energy removal temperature control mechanisms.

[00138] In the following, referring to Fig. 9, a temperature control unit 900 according to an exemplary embodiment will be explained.

[00139] In the embodiment of Fig. 9, a container 901 is provided in which the portion between the first frit 205 and the second frit 206 of the column tube 202 is dipped or immersed. Within the container 901 , a heating fluid 902 is provided which surrounds an outer circumference of the column tube 202, and which may be a thermally well- conducting material. The heating fluid 902 may also serve as a cooling fluid and may be an immersion heater or a boiling device. Therefore, a selective supply of thermal energy to outer portions of an interior of the column tube 202 may be ensured.

[00140] In the following, referring to Fig. 10, a temperature control unit 1000 according to an exemplary embodiment will be explained.

[00141] In the embodiment of Fig. 10, the column tube 202 is surrounded by a hollow cylindrically shaped electromagnetic radiation source 1001 adapted to generate electromagnetic radiation 1002 of an adjustable wavelength. The electromagnetic radiation 1002 is adapted to transmit the electromagnetic radiation 1002 to the column tube 202 to be absorbed predominantly by circumferentially outer portions of a fluidic sample flowing in direction 215 through an interior bore of the column tube 202. For instance, the wavelength may be in the infrared, ultraviolet or microwave frequency region, wherein the selection of the wavelength may influence the penetration depth of the radiation into the cylindrical fluid sample body. Thus, adjusting the wavelength and/or intensity of the radiation may allow to be used as a design parameter for controlling the thermal energy transfer to thereby equilibrate a temperature profile.

[00142] In the following, referring to Fig. 11 , an exemplary embodiment of a temperature control unit 1100 will be explained.

[00143] The embodiment of Fig. 11 is similar to the embodiment of Fig. 5. However, the temperature control unit 1100 uses a ,,tube-in-tube" architecture in which an electrically conductive inner tube 1101 is located within an electrically insulating outer tube 202. By applying an alternating voltage (using the voltage supply unit 502) to a coil 501 surrounding both tubes 202, 1101 , an exterior inductive heating of the electrically conductive inner tube 1101 is possible (the electrically conductive inner tube 1101 may therefore be considered as one secondary winding).

[00144] 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.

Claims

1. A temperature compensation unit (216) for a fluidic device (200) for analyzing a fluidic sample, wherein the fluidic device (200) is adapted to conduct the fluidic sample along a first direction (215) in the fluidic device (200),

the temperature compensation unit (216) being adapted to at least partially compensate a temperature profile in the fluidic device (200) along a second direction (217) which differs from the first direction (215).

2. The temperature compensation unit (216) according to claim 1 , comprising at least one of:

the temperature compensation unit (216) is adapted to at least partially compensate a temperature profile in the fluidic device (200) originating from friction between the fluidic sample flowing in the fluidic device (200) and a stationary packing material (214) filled in the fluidic device (200);

the first direction (215) is essentially perpendicular to the second direction (217);

the second direction (217) is part of a plane being aligned essentially perpendicular to the first direction (215), and the temperature compensation unit (216) is adapted to at least partially compensate the temperature profile within the plane.

3. The temperature compensation unit (216) according to claim 1 or any one of the above claims,

wherein the fluidic device (200) comprises a tube (202) and is adapted to conduct the fluidic sample along a longitudinal direction (215) of the tube (202);

wherein the temperature compensation unit (216) is adapted to at least partially compensate the temperature profile in the fluidic device (200) along a radial direction (217) of the tube (202).

4. The temperature compensation unit (216) according to claim 1 or any one of the above claims, comprising a thermal energy source for selectively supplying thermal energy to a first component of the fluidic sample which is colder than a second component of the fluidic sample.

5. The temperature compensation unit (216) according to claim 4,

wherein the thermal energy source is adapted for applying a temperature profile between an inner portion within the fluidic device (200) and an outer portion within the fluidic device (200) by supplying more thermal energy to the outer portion than to the inner portion.

6. The temperature compensation unit (216) according to claim 1 or any one of the above claims,

wherein the temperature compensation unit (800) comprises a mechanical barrier (801 ) designed and positioned for selectively redirecting different components of the fluidic sample at least partially along the second direction (217) to thereby modify a flowing profile of the components to at least partially compensate the temperature profile.

7. The temperature compensation unit (216) according to claim 1 or any one of the above claims,

wherein the temperature compensation unit (800) comprises a mechanical barrier (801 ) designed and positioned for selectively mixing different components of the fluidic sample to thereby modify a flowing profile of the components to at least partially compensate the temperature profile.

8. The temperature compensation unit (216) according to claim 1 or any one of the above claims,

wherein the temperature compensation unit (216) is adapted to at least partially compensate the temperature profile using at least one mechanism of the group consisting of heat conduction, heat convection, and heat radiation.

9. The temperature compensation unit (216) according to claim 1 or any one of the above claims, wherein the temperature compensation unit (216) is adapted to at least partially compensate a temperature profile in the fluidic device (200) along the first direction (215).

10. The temperature compensation unit (216) according to claim 1 or any one of the above claims,

wherein the temperature compensation unit (600) comprises a thermal energy sink (601 , 602) for selectively absorbing thermal energy from a first component of the fluidic sample which is hotter than a second component of the fluidic sample.

11. A fluidic device (200) for analyzing a fluidic sample, wherein the fluidic device (200) is adapted to conduct the fluidic sample along a first direction (215) in the fluidic device (200), the fluidic device (200) comprising

a temperature compensation unit (216) according to claim 1 or any one of the above claims for at least partially compensating a temperature profile in the fluidic device (200) along a second direction (217) which differs from the first direction (215).

12. The fluidic device (200) according to claim 11 , comprising at least one of:

a sensor for measuring the temperature profile in the fluidic device (200) along the second direction (217), and a regulator unit for regulating the temperature compensation unit (216) for compensating the temperature profile based on a measurement performed by the sensor;

the fluidic device (200) is adapted as a fluid separation system for separating compounds of the fluidic sample;

the fluidic device (200) is adapted as a fluid purification system for purifying the fluidic sample;

the fluidic device (200) is adapted to analyze at least one physical, chemical and/or biological parameter of at least one compound of the fluidic sample;

the fluidic device (200) comprises at least one of the group consisting of a sensor device, a test device for testing a device under test or a substance, 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, and a mass spectroscopy device;

the fluidic device (200) comprises a chromatographic column (201 ) for separating components of the fluidic sample;

the fluidic device (200) is adapted to conduct a liquid sample along the first direction (215);

the fluidic device (200) is adapted to conduct the fluidic sample in the fluidic device (200) with a high pressure;

the fluidic device (200) is adapted to conduct the fluidic sample in the fluidic device (200) with a pressure of at least 100 bar, particularly of at least 500 bar.

13. The fluidic device (200) according to claim 11 or any one of the above claims,

comprising a column (201 ) comprising a column tube (202) and the temperature compensation unit (216).

14. The fluidic device (200) according to claim 13,

wherein the temperature compensation unit (216) comprises a thermal energy source for providing thermal energy to components of the fluidic sample in dependence of a radial distance of a component from a center of the column tube (202).

15. The fluidic device (200) according to claim 14,

wherein the thermal energy source is adapted for providing less thermal energy to components of the fluidic sample which are located closer to the center of the column tube (202) as compared to components of the fluidic sample which are located further away from the center of the column tube (202).

16. The fluidic device (200) according to claim 14 or any one of the above claims, wherein the thermal energy source comprises a heating wire (701 ) wound in at least one manner of the group consisting of being wound along an inner surface of the column tube (202), being wound along an outer surface of the column tube (202), and being accommodated in an interior of the column tube (202).

17. The fluidic device (200) according to claim 14 or any one of the above claims,

wherein the thermal energy source comprises a heating fluid stream generating element for generating a heated fluid stream to be brought in thermal contact with the column tube (202).

18. The fluidic device (200) according to claim 14 or any one of the above claims,

wherein the thermal energy source comprises an electromagnetic radiation generation unit (1001 ) for generating electromagnetic radiation (1002).

19. The fluidic device (200) according to claim 14 or any one of the above claims,

wherein the thermal energy source comprises an electromagnetic radiation generation unit (1001 ) for generating electromagnetic radiation (1002), wherein the electromagnetic radiation generation unit (1001 ) is adapted for generating electromagnetic radiation (1002) of at least one of the group consisting of ultraviolet radiation, optical light, infrared radiation, microwaves and high frequency radiation.

20. The fluidic device (200) according to claim 14 or any one of the above claims,

wherein the thermal energy source comprises an ultrasound generation unit for generating ultrasound radiation.

21. The fluidic device (200) according to claim 14 or any one of the above claims,

wherein the thermal energy source comprises a primary inductive coupling element (501 ) for providing an alternating electrical signal, and comprises a secondary inductive coupling element (503) located at or in the column tube

(202) and inductively coupled to the primary inductive coupling element (501 ).

22. The fluidic device (200) according to claim 14 or any one of the above claims, wherein the thermal energy source comprises a primary inductive coupling element (501 ) located outside of the column tube (202) for providing an alternating electrical signal, and comprises a secondary inductive coupling element (503) located at or in the column tube (202) and inductively coupled to the primary inductive coupling element (501 ), wherein the secondary inductive coupling element (503) comprises at least one of the group consisting of one or more metal rings located at or in the column tube (202), and a metallic coil located at or in the column tube (202).

23. The fluidic device (200) according to claim 11 or any one of the above claims, comprising at least one of:

the column tube (202) has an essentially cylindrical bore, and the temperature compensation unit (216) is adapted for compensating the temperature profile in a radial direction of the essentially cylindrical bore;

the temperature compensation unit (216) comprises a temperature profile generating element for generating a longitudinal temperature profile along the first direction (215);

at least a part of the column tube (202) is filled with a fluid separating material (214);

at least a part of the column tube (202) is filled with a fluid separating material (214), the fluid separating material (214) comprises beads having a size in the range of essentially 1 μm to essentially 50 μm;

at least a part of the column tube (202) is filled with a fluid separating material (214), the fluid separating material (214) comprises beads having pores having a size in the range of essentially 0.02 μm to essentially 0.03 μm;

the column tube (202) comprises at least one material of the group consisting of steel, ceramics, quartz, and glass.

24. The fluidic device (200) according to claim 11 or any one of the above claims, comprising at least one of: the temperature compensation unit (600) comprises a thermal energy sink (601 , 602) for absorbing thermal energy from components of the fluidic sample in dependence of a distance of a component from a center of the column tube (202);

the temperature compensation unit (600) comprises a thermal energy sink (601 ,

602) for absorbing thermal energy from components of the fluidic sample in dependence of a distance of a component from a center of the column tube (202), wherein the thermal energy sink is adapted for absorbing more thermal energy from components of the fluidic sample which are located closer to the center of the column tube (202) as compared to components of the fluidic sample which are located further away from the center of the column tube (202);

25. A method of treating a fluidic sample, the method comprising

forcing the fluidic sample to flow along a first direction (215),

at least partially compensating a temperature profile of the fluidic sample along a second direction (217) which differs from the first direction (215).