FLUID SUPPLY DEVICES AND FLUID MEMBER FOR FORMING A MOBILE PHASE FOR A SAMPLE SEPARATING DEVICE

Abstract

A fluid supply device for providing a mobile phase for a sample separating device includes, a supply conduit for providing a fluid which forms at least a part of the mobile phase, a fluid valve which is fluidically coupled with the supply conduit and, depending on its switching state, enables or prevents a passing of the fluid from the supply conduit, an elastic buffer unit which is fluidically coupled upstream of the fluid valve with the supply conduit and which is configured for buffering the fluid, and a fluid conveying unit for conveying the fluid which passes the fluid valve.

Claims

1. A fluid supply device for providing a mobile phase for a sample separating device, the fluid supply device comprising: a supply conduit for providing a fluid which forms at least a part of the mobile phase; a fluid valve which is fluidically coupled with the supply conduit and, depending on its switching state, enables or prevents a passing of the fluid from the supply conduit; an elastic buffer unit which is fluidically coupled upstream of the fluid valve with the supply conduit and which is configured for buffering the fluid; and a fluid conveying unit for conveying the fluid which is passing the fluid valve.

2. The fluid supply device according to claim 1, comprising: at least one further supply conduit for providing at least one further fluid which forms at least a further part of the mobile phase; at least one further fluid valve which is fluidically coupled with the at least one further supply conduit and, depending on its switching state, enables or prevents a passing of the at least one further fluid from the at least one further supply conduit; and at least one further elastic buffer unit which is fluidically coupled upstream of the at least one further fluid valve with the at least one further supply conduit and which is configured for buffering the at least one further fluid, wherein the fluid conveying unit is configured for conveying the at least one further fluid which passes the at least one further fluid valve, such that the mobile phase is formed of the fluid and the at least one further fluid.

3. The fluid supply device according to claim 1, wherein the buffer unit comprises a variable buffer volume and an elastic compensating element which is at least partially delimiting the buffer volume, which is configured for elastically compensating pressure fluctuations in the supply conduit.

4. The fluid supply device according to claim 1, wherein the buffer unit comprises one of: a sensor unit for detecting a sensor information which is related to the fluid in the supply conduit; a sensor membrane for detecting a sensor information which is related to the fluid in the supply conduit.

5. The fluid supply device according to claim 4, wherein the sensor information is selected from the group consisting of: a pressure of the fluid in the supply conduit; a flow rate of the fluid in the supply conduit; a density of the fluid in the supply conduit; and a temperature of the fluid in the supply conduit.

6. The fluid supply device according to claim 1, wherein the buffer unit comprises one of: an actor unit for acting of the buffer unit on the fluid; an actor membrane for acting of the buffer unit on the fluid.

7. The fluid supply device according to claim 6, wherein acting on the fluid is selected from the group consisting of: a change of the elasticity of the buffer unit between a more rigid and a more flexible configuration; and a force application.

8. The fluid supply device according to claim 1, wherein the buffer unit comprises a tempering unit for tempering the fluid so as to heat and/or cool the fluid.

9. The fluid supply device according to claim 1, wherein the buffer unit comprises an electroactive polymer configured as at least a part of a sensor unit and/or an actor unit of the buffer unit.

10. The fluid supply device according to claim 1, wherein the buffer unit is actively controllable by a control unit configured to apply an electric signal to the buffer unit.

11. An integrally formed fluid member for combining and mixing fluids for forming a mobile phase in a fluid supply device, the integrally formed fluid member comprising: a plurality of fluid inlets, wherein a respective fluid is suppliable at each of the fluid inlets; a fluid combining unit for combining the fluids which are supplied at the fluid inlets; and a mixing unit for mixing the combined fluids and for providing the mixed fluids as mobile phase at a fluid outlet, wherein the mixing unit is a passive mixing unit without movable parts.

12. The integrally formed fluid member according to claim 11, comprising at least one of the following features: configured as stiff body with fluid channels which extend originating from the fluid inlets via at least one combining position of the fluids and then through the mixing unit up to the fluid outlet; wherein the fluid member is shaped as a plate and/or is configured as an injection molded part or as a laminate; wherein the fluid combining unit comprises inlet channels which are fluidically coupled with the fluid inlets, which are combined to a single outlet channel at a combining position, which leads to the mixing unit; wherein the fluid combining unit comprises inlet channels which are fluidically coupled with the fluid inlets, which are combined to a single outlet channel at a combining position, which leads to the mixing unit, wherein the inlet channels and the combining position form a substantially X-shaped fluidic structure or an array of, in particular substantially X-shaped, introducing structures; wherein the mixing unit is configured for splitting the combined fluids into multiple separate fluid streams in different mixing channels and for recombining the fluid streams from the mixing channels to the mixed mobile phase; wherein the mixing unit is configured for splitting the combined fluids into multiple separate fluid streams in different mixing channels and for recombining the fluid streams from the mixing channels to the mixed mobile phase, wherein the different mixing channels are configured to predetermine different flow times for the different flow streams; wherein the mixing unit is configured as elongated structure; wherein the fluid member comprises a sensor unit for detecting a sensor information which is related to the single fluids and/or the mobile phase, wherein the sensor information is selected from the group consisting of: a pressure of the single fluids and/or the mobile phase; a flow rate of the single fluids and/or the mobile phase; and a temperature of the single fluids and/or the mobile phase; wherein the fluid member comprises a tempering unit for tempering the single fluids and/or the mobile phase so as to heat and/or cool the single fluids and/or the mobile phase; which is made of one material; wherein the fluid combining unit is configured for splitting each fluid which is supplied at a respective one of the fluid inlets into multiple respective partial channels, and is further configured to combine the partial channels which are assigned to different ones of the fluids at each of a plurality of combining positions, to thereby obtain a respective combined flow of the different fluids at each of the combining positions, and wherein the fluid combining unit is further configured to supply the flows which are combined at the combining positions to the mixing unit for mixing.

13. A fluid supply device for providing a mobile phase for a sample separating device, the fluid supply device comprising: a plurality of supply conduits, wherein each supply conduit is configured for providing a respective fluid which commonly form the mobile phase; a plurality of fluid valves, wherein each fluid valve is fluidically coupled with a respective one of the supply conduits, and wherein each fluid valve, depending on its switching state, enables or prevents a passing of the respective fluid from the respective supply conduit; an integrally formed fluid member according to claim 11, whose fluid inlets are coupled with the fluid valves and at whose fluid outlet the mobile phase is provided; and a fluid conveying unit which is fluidically coupled with the fluid outlet for conveying the mobile phase.

14. A fluid supply device for providing a mobile phase for a sample separating device, the fluid supply device comprising: a plurality of supply conduits, wherein each supply conduit is configured for providing a respective fluid which commonly form the mobile phase; a plurality of fluid valves, wherein each fluid valve is fluidically coupled with a respective one of the supply conduits, and wherein each fluid valve, depending on its switching state, enables or prevents a passing of the respective fluid from the respective supply conduit; a fluid combining unit for combining the fluids which are passing the fluid valves at a combining position for forming the mobile phase; and a fluid conveying unit which is fluidically coupled with the combining position for conveying the mobile phase, wherein between the fluid valves and the combining position a such dimensioned compensating volume is formed, that even in the case of a maximum fluid reflow from the fluid conveying unit in the direction of the fluid valves, reaching the fluid valves by the fluid reflow is made impossible due to the compensating volume.

15. The fluid supply device according to claim 14, wherein the fluid combining unit comprises inlet channels between the fluid valves and the combining position, whose common inner volume forms the compensating volume.

16. The fluid supply device according to claim 14, wherein the compensating volume is selected from the group consisting of: at least 5 μL; at least 10 μL; and at least 30 μL.

17. The fluid supply device according to claim 2, comprising at least one of the following features: comprising a plurality of fluid component sources, wherein each fluid component source is fluidically coupled with a respective supply conduit for providing the respective fluid; wherein the fluid valves form a proportioning unit for proportioning fluid packages of the different fluids which are supplied by the supply conduits; wherein the fluid valves form a multichannel gradient valve.

18. The fluid supply device according to claim 1, comprising at least one of the following features: wherein the fluid conveying unit is configured for drawing the mobile phase; wherein the fluid conveying unit is configured for conveying the mobile phase with a pressure of at least 500 bar or at least 1200 bar; wherein the fluid conveying unit comprises a piston pump or a plurality of serial and/or parallel piston pumps; wherein the fluid conveying unit is selected from the group consisting of: a double piston pump; a binary pump; a quaternary pump; and a multichannel pump.

19. A sample separating device for separating a fluidic sample, wherein the sample separating device comprises: a fluid supply device according to claim 1 for providing a mobile phase, wherein the fluidic sample is to be injected into the mobile phase; and a sample separating unit which is configured for separating the fluidic sample which is injected into the mobile phase.

20. The sample separating device according to claim 19, further comprising at least one of the following features: the sample separating unit is configured as chromatographic separating unit; the sample separating device is configured for analyzing at least one physical, chemical and/or biological parameter of at least one fraction of the fluidic sample; the sample separating device comprises at least one of the group consisting of: a device for chemical, biological and/or pharmaceutical analysis; a chromatographic device; a liquid chromatographic device; and an HPLC device; the sample separating device is configured as microfluidic device; the sample separating device is configured as nanofluidic device; the sample separating device comprises a detector for detecting the separated sample; the sample separating device comprises an injector for injecting the fluidic sample into the mobile phase; the sample separating device comprises a sample fractionator for fractionating the separated sample.

Description

BRIEF DESCRIPTION OF THE DRAWING FIGURES

[0064] Other objects and many of the accompanying advantages of embodiments of the present invention are easier to recognize and better to understand with reference to the following detailed description of embodiments in conjunction with the accompanying drawings. Features which are substantially or functionally the same or similar, are provided with the same reference signs.

[0065] FIG. 1 shows a HPLC-system with a fluid supply device according to an exemplary embodiment of the invention.

[0066] FIG. 2 shows an integrally formed fluid member of a fluid supply device according to an exemplary embodiment of the invention.

[0067] FIG. 3 shows an integrated mixing unit of the integrally formed fluid member according to FIG. 2.

[0068] FIG. 4 shows a fluid supply device with a valve protection against pump reflow according to an exemplary embodiment of the invention.

[0069] FIG. 5 shows a fluid supply device with a plate-shaped integrally formed fluid member according to another exemplary embodiment of the invention.

[0070] FIG. 6 shows a fluid supply device with buffer units in supply conduits according to still another exemplary embodiment of the invention.

[0071] FIG. 7 shows a buffer unit of a fluid supply device according to an exemplary embodiment of the invention.

[0072] FIG. 8 shows a buffer unit of a fluid supply device according to another exemplary embodiment of the invention.

[0073] FIG. 9 shows a buffer unit of a fluid supply device according to still another exemplary embodiment of the invention.

[0074] FIG. 10 shows a fluid combining unit with a subsequent mixing unit for a preferably integrally formed fluid member according to an exemplary embodiment of the invention.

[0075] The illustration in the drawing is schematic.

DETAILED DESCRIPTION

[0076] Before referring to the drawing figures exemplary embodiments are described, some basic considerations shall be summarized, based on which exemplary embodiments of the invention have been derived.

[0077] According to a first aspect of an embodiment of the invention, in fluid connection with a supply conduit and still in front of a fluid valve, an elastic buffer unit may be implemented, which, as fluidic capacity, may have a damping and compensating effect, respectively. Such a buffer between a solvent bottle and the inlet valve enables precise inlet volumes. An active buffer, for example configured by an electroactive polymer, enables a precise determination and specification, respectively, of the volume stream. Such a preferably active elastic buffer unit may advantageously comprise a sensor (in particular for capturing the pumping pressure, the density of a mobile phase, etc.) and/or an actor or actuator (in particular for adjusting the stiffness of the buffer unit). Such a sensor may be configured as a sensor membrane, for example. Such an actor may be configured as an actor membrane, for example. By providing a buffer unit with flexible and reliably adjustable, respectively, inner volume per supply conduit, solvent containers may be brought in close vicinity to a pump, such that a distance between the solvent container and the solvent inlet may be shortened. This improves the introducing behavior and prevents an undesired delay in the solvent supply which may conventionally lead to an undesired deviation of an actual composition of a mobile phase from a target composition.

[0078] According to a second aspect of an embodiment of the invention, a fluid member which is configured in an integrally formed manner or made of one piece, may accomplish both, combining multiple fluid flows and mixing. By such a member combination of a manifold with a mixer to a preferably stiff member, undesired missing volumes may be reliably prevented. Thus, in an advantageous manner, a space-saving integration of an entire multichannel gradient valve into a physical unit may be accomplished. In particular, in this respect, a use of a liquid crystal polymer (LCP) may be advantageous. For example, a mixer with an integrated distributor and passive damping may be provided.

[0079] According to a third aspect of an embodiment of the invention, a reflow volume between fluid valves and a fluid conveying unit of a fluid supply device may be provided, to receive mixed solvent which is pushed out of the pump in the backward direction before the inlet valve can close. Descriptively, a sufficiently large compensating volume may be implemented for the protection from a pump reflow.

[0080] Conventionally, a position where a gradient valve combines different solvents may be arranged in a separate member of the gradient valve. This leads to a high complexity and to a construction which is prone to errors and elaborate. Conventionally, the distributor may be integrated in a valve block and separated from the mixer which is a further assembly. In this way, problems in the connection of the different assemblies arise. Such a conventional valve block has to be precisely manufactured with small tolerances, which increases the manufacturing effort and the risks for an erroneous operation. Since a conventional design of a sealing position (in particular a valve) may receive too little volume up to combining the different channels (manifold position), an undesired reflow of the pump may lead to a failure of the valve. The mixed solvent is removed behind a seal position, which may trigger undesired chemical reactions. For example, conventionally, salt crystals may form which block the valve, or a polymerization may occur, whereby the valve may adhere. The mixer has to be connected via fluidic connection elements, which increases both, the effort and the risk for errors. A further problem of conventional fluid supply devices is that the entire liquid from solvent containers has to be accelerated along a long fluidic path up to a mixer, which has an adverse effect on the performance and promotes undesired pressure waves. The latter is disadvantageous for the performance of the valve.

[0081] According to an exemplary embodiment of the invention, the mixer and the element which combines the (for example four) fluid channels may be combined in a common member. This integrally formed member may be a planar structure or micro-processed or structured polymer foils (for example made of liquid crystal polymer), for example. Additionally, for improving the performance, an intelligent damper in form of a fluidic capacity and in form of an elastic buffer element, respectively, may be placed in front of a multichannel gradient valve.

[0082] According to an embodiment of the invention, a simplified assembly may thus be provided and a protection volume for each fluid channel may be provided. Additionally, an active damper may decouple the multichannel gradient valve from a solvent conduit with respect to excitations and mass inertia, which suppresses pressure pulses and improves the performance of the multichannel gradient valve compared to conventional embodiments.

[0083] An integrally formed fluid member for a fluid supply device according to an exemplary embodiment of the invention may provide (for example four) defined inlets from the multichannel gradient valve and a protection volume which may be dimensioned larger than or equal to a maximum reflow of the pump and all actors between a distributor position and the pump inlet. This means that an undefined composition cannot be rinsed beyond the seal position of the valve, whereby an undesired crystallization and a failure of the valve may be reliably avoided. Since the volume of the distributor is fixed and the tubes or fluid ports in the integrally formed member are dispensable, heating devices, cooling devices, temperature sensors, sensors (for example flow sensors and/or pressure sensors) for measuring defined solvent attributes may be utilized.

[0084] Since exemplary embodiments of the invention enable large diameters of the hydraulic conduits, tolerances or roughness have less impact on the pump performance. In order to accelerate a suction operation of the mobile phase through a fluid conveying unit and to decouple from the solvent conduit of the solvent containers, advantageously elastic buffer units which are configured as hydraulic capacities decouple the solvent containers and their fluid conduits from the rest of the system. During a fast reception, the liquid is mainly delivered from the capacity. Thus, it is dispensable to accelerate the rest of the fluid conduit. An elastic buffer unit which is configured as fluidic capacity may be made of a fluid reception volume which may be sealed with an elastic membrane (for example made of a perfluoro-elastomer or perfluorinated rubber (FFKM) or silicone) with a sensor layer. A sensor layer of such an elastic buffer unit may be manufactured as strain gauge or from a dielectric silicone or polymer, for example. This enables a measurement of the pressure drop, when a defined fluid reception is performed by the pump, for example. When the elasticity of the membrane and the bending are known, a pressure drop, pressure peaks, pressure waves or even a blocking of filters may be avoided. When using an electroactive polymer, for example made of silicone, the sensor element may also be configured as an actor. In particular, thereby, a bias of the damper may be dynamically adjusted.

[0085] Exemplary embodiments of the invention may provide fluid supply devices for a multichannel gradient valve which may be an inlet valve arrangement in front of a chromatographic pump for generating a solvent mixture. In particular, in each fluid channel from a respective solvent bottle to a switching valve for this fluid channel, a fluidic buffer unit may be implemented. Such a buffer volume may serve for overcoming limitations which are resulting from the fact that fluidic restrictions are unavoidable in the supply conduit from the solvent container to the valve. In operation, such restrictions may lead to the fact that the solvent cannot be accelerated in an arbitrarily fast manner, which may lead to a certain delay and thus in particular at small volumes to an erroneous dosing or metering. According to an exemplary embodiment of the invention, this may be avoided by a respective buffer volume in a respective fluid conduit. Such a fluid-elastic buffer unit thus leads to an improvement of the accuracy of the solvent composition. In particular, the buffer unit may be an active buffer in front of a respective switching valve.

[0086] FIG. 1 shows the setup of an HPLC-system in principle as example for a liquid chromatography sample separating device 10 according to an exemplary embodiment of the invention, as it may be used for a liquid chromatography, for example. A fluid conveying unit 20 which is supplied with solvents from a supply unit 25 drives a mobile phase through a sample separating unit 30 (such as a chromatographic column, for example) which contains a stationary phase. The supply unit 25 encompasses a first fluid component source 156 for providing a first fluid or a first solvent component A (for example water) and a second fluid component source 157 for providing another second fluid or a second solvent component B (for example an organic solvent). An optional degasser 27 may degas the solvents which are provided by the first fluid component source 156 and by the second fluid component source 157, before these are supplied to the fluid conveying unit 20. A sample application unit 40, which may also be denoted as injector, is arranged between the fluid conveying unit 20 and the sample separating unit 30, to introduce a sample liquid or a fluidic sample into the fluidic separating path. For this purpose, an injector valve 90 may be correspondingly switched. The stationary phase of the sample separating unit 30 is provided for the purpose to separate the components of the sample. A detector 50 which may comprise a flow cell detects separated components of the sample, and a fractionating device 60 may be intended for dispensing the separated components of the sample into containers which are provided for this purpose. Liquids which are no longer required may be dispensed into a drain container or a waste (not shown).

[0087] While a liquid path between the fluid conveying unit 20 and the sample separating unit 30 is typically under high pressure, the sample liquid under normal pressure is at first introduced in a region which is separated from the liquid path, a so-called sample loop of the sample application unit 40 or of the injector, which in turn introduces the sample liquid into the liquid path under high pressure. While connecting the sample liquid which is at first under normal pressure in the sample loop into the liquid path under high pressure, the content of the sample loop is brought to the system pressure of the sample separating device 10 which is configured as HPLC. A control unit 70 controls the single members 20, 30, 40, 50, 60, 90 and the fluid valves 106, 107 which are described in more detail below, and active elastic buffer units 110 of the sample separating device 10.

[0088] FIG. 1 also shows a liquid chromatography fluid supply device 100 for providing a mixture of multiple different fluids as solvent composition or mobile phase for the liquid chromatography sample separating device 10. The fluid supply device 100 comprises in the shown embodiment two supply conduits 102, 103, wherein each is fluidically coupled with a respective one of the two solvent containers which are denoted as fluid component sources 156, 157 for providing a respective one of the fluids or solvent components A and B. The respective fluid or the respective solvent component A and/or B is conveyed through the respective supply conduit 102 and/or 103 through the degasser 27 and through a respective elastic buffer unit 110 to a respective fluid valve 106 and/or 107. Behind the fluid valves 106, 107, an integrally formed fluid member 130 is located, at which the fluids or solvent components A and/or B from the supply conduits 102, 103 are combined with each other and are mixed. Behind the fluid valves 106, 107 which are configured as proportioning units, the fluid packages from the supply conduits 102, 103 thus merge under formation of a homogeneously mixed solvent composition. The latter is supplied to the fluid conveying unit 20.

[0089] The fluid supply device 100 according to FIG. 1 has numerous advantageous properties: firstly, providing a conduit-specific elastic buffer unit 110 in each of the fluid conduits 102, 103 leads to a damping of pressure fluctuations and/or pressure pulses and thus to a more correct solvent composition. Since each of the buffer units 110 is actively controllable by the control unit 70, the rigidity and/or flexibility of an elastic element of a respective buffer unit 110 may be adjusted in a desired manner. Integrating a fluid combining function for combining the solvents from the fluid conduits 102, 103 and a mixing function of these solvent streams in the integrally formed fluid member 130 leads to a compact configuration and to an error-robust operation. By selecting an inner volume of the integrally formed fluid member 130 to be sufficiently large, even in case of a temporal reflow of mobile phase from the fluid conveying unit 20 back into the fluid member 130, it may be reliably prevented that the mobile phase flows back into the valves 106 and/or 107 and the valve seals are damaged or destroyed by crystallizing the mobile phase. These advantageous properties which all act together for enabling a correct and precise solvent composition are described in more detail below.

[0090] FIG. 2 shows an integrally formed fluid member 130, which is configured as a stiff body 142, of a fluid supply device 100 according to an exemplary embodiment of the invention.

[0091] The integrally formed fluid member 130 which is illustrated in FIG. 2 fulfills a double function, namely combining and mixing fluids for forming a mobile phase in the fluid supply device 100. For this purpose, the integrally formed fluid member 130 comprises four fluid inlets 132 to 135, wherein at each of the fluid inlets 132 to 135, a respective fluid is suppliable. Each of the fluid inlets 132 to 135 is connectable or connected with a respective one of four fluid valves 106 to 109 which are illustrated in FIG. 4. Furthermore, a fluid combining unit 136 which is substantially X-shaped is provided for combining the fluids which are supplied at the fluid inlets 132 to 135. Moreover, in the interior of the member 130, a mixing unit 138 for mixing the combined fluids and for providing the mixed fluids as mobile phase at a fluid outlet 140 of the fluid member 130 is fluidically connected to the fluid combining unit 136. Said fluid combining unit 136 comprises inlet channels 144 to 147 which are fluidically coupled with the fluid inlets 132 to 135. The inlet channels 144 to 147 are combined at a fluidic combining position 148 to a single outlet channel 150 which leads to the mixing unit 138 for mixing the combined fluids or solvent components. As illustrated in FIG. 2, the inlet channels 144 to 147 and the combining position 148 form a substantially X-shaped fluidic structure. As illustrated schematically in FIG. 2 and in detail in FIG. 3, the mixing unit 138 may be configured as elongated structure.

[0092] The fluid member 130 may be configured as a compact stiff body 142 with fluid channels 144 to 147, 150, 152 (see FIG. 3) and may be shaped as a plate and/or configured as an injection molded part or a laminate member. For example, the fluid member 130 may be manufactured from one material made of plastic.

[0093] Despite not being shown for the fluid member 130 in the drawing figures, the fluid member 130 may comprise one or more sensor units for detecting a sensor information related to the single fluids and/or the still unmixed or already mixed mobile phase, in a respective one of the inlet channels 144 to 147 and/or at channels (see reference sign 152 in FIG. 3) of the mixing unit 138, for example. For example, by such a sensor unit, a pressure of the single fluids and/or the still unmixed or already mixed mobile phase, a flow rate of the single fluids and/or the still unmixed or already mixed mobile phase, and/or a temperature of the single fluids and/or the still unmixed or already mixed mobile phase may be captured. Also not shown in the drawing figure is that the fluid member 130 may comprise a tempering unit for heating and/or cooling the single fluids and/or the still unmixed or already mixed mobile phase.

[0094] The fluid member 130 which is illustrated in FIG. 2 may be integrated in a fluid supply device 100 for providing a mobile phase for a sample separating device 10 in the manner shown in FIG. 4 or FIG. 6, for example. For this purpose, the fluid inlets 132 to 135 of the fluid member 130 may be fluidically connected to outlets of the respective fluid valves 106 to 109. A fluid outlet 140 of the mixing unit 138 of the fluid member 130 may be fluidically connected to an inlet of a fluid conveying unit 20 which is configured as a chromatographic high pressure pump, for example. Thus, at the fluid outlet 140 of the fluid member 130, the correctly composited and already mixed mobile phase is provided for further processing (in particular for compressing and conveying) by the fluid conveying unit 20. For example, the fluid conveying unit 20 may convey the mobile phase with a pressure of at least 1000 bar, for example 1200 bar. For example, the fluid conveying unit 20 may be configured as a piston pump or a plurality of serial or parallel piston pumps, in particular as double piston pump.

[0095] FIG. 3 shows the integrated mixing unit 138 of the integrally formed fluid member 130 according to FIG. 2.

[0096] A fluid inlet of the mixing unit 138 corresponds to an outlet channel 150 of the fluid combining unit 136 and/or is fluidically coupled with it. The mixing unit 138 which is illustrated in FIG. 3 is a purely passive and thus error-robust mixer which at first splits the combined fluids into multiple separate fluid streams in different mixing channels 152 and combines the split fluid streams in the mixing channels 152 after passing the same to the mixed mobile phase under combining the single fluid streams. The different mixing channels 152 are configured to predetermine different flow times for the different fluid streams. This is realized according to FIG. 3 by differently long mixing channels 152 between a splitting position 160 and a combining position 162. Alternatively or supplementary, different flow times of the mixing channels 152 may also be accomplished by a variation of their inner diameters, by the implementation of fluidically delayed restrictions in the mixing channels 152, etc. In a sequence of subsequent solvent packages of the different solvents from the inlet channels 144 to 147 corresponding to a sequential switching logic of the fluid valves 106 to 109, the solvent packages may be split into the different mixing channels 152 and may be effectively mixed with each other due to the differently long flow times at the combining position 162.

[0097] FIG. 4 shows a fluid supply device 100 according to an exemplary embodiment of the invention.

[0098] The fluid supply device 100 according to FIG. 4 shows at first four supply conduits 102 to 105, wherein each of which is configured for providing a respective fluid which commonly form the mobile phase. The single fluids may be solvents which are provided by solvent containers which may be fluidically connected to a respective one of the supply conduits 102 to 105 (compare FIG. 6). Furthermore, four fluid valves 106 to 109 are illustrated, wherein each of which is fluidically coupled with a respective one of the supply conduits 102 to 105. Each of the fluid valves 106 to 109 may be individually controlled, for example opened or closed, by a control unit (see reference sign 70 in FIG. 1). The fluid valves 106 to 109 commonly with the control unit 70 form a proportioning unit for proportioning fluid packages of the different fluids which are supplied by the supply conduits 102 to 105. More precisely, the fluid valves 106 to 109 commonly form a multichannel gradient valve. When the fluid conveying unit 20 draws at the fluid inlets 132 to 135 downstream of the fluid valves 106 to 109, the respective fluid or solvent from one of the supply conduits 102 to 105, whose assigned fluid valve 106 to 109 is presently open, may be sucked into the fluid member 130. In other words, each of the fluid valves 106 to 109, depending on its switching state (for example open or closed), enables passing the respective fluid from the respective supply conduit 102 to 105 or prevents it. When at a certain instant in time, respectively exactly one of the fluid valves 106 to 109 is open, and when at this instant in time, the respective others of the fluid valves 106 to 109 are closed, a sequence of subsequent fluid packages of different solvents (for example water, ethanol, acetonitrile, etc.) flows through the outlet channel 150. The fluid combining unit 136 serves for combining the fluids which are passing the fluid valves 106 to 109 at a combining position 148 for forming the mobile phase. In the mixing unit 138, the fluid packages of the single solvents are mixed to a homogenous mobile phase and are provided to a fluid conveying unit 20 which is fluidically coupled with the fluid outlet 140 for conveying the mobile phase.

[0099] Advantageously, between the fluid valves 106 to 109 and the mixing unit 138, a such dimensioned compensating volume 112 in form of the inner volume of the inlet channels 144 to 147 is formed, that even in the case of a maximum fluid reflow from the fluid conveying unit 20 in the direction of the fluid valves 106 to 109, reaching the fluid valves 106 to 109 by the fluid reflow is fluidically made impossible due to the compensating volume 112. In other words, the inner volume of the inlet channels 144 to 146 is selected to be sufficiently large, that even under worst circumstances, a reflow of the mobile phase from the fluid conveying unit 20 into the inlet channels 144 to 147 can never reach up into the fluid valves 106 to 109 due to the described dimensional configuration. Undesired crystallizing of the mobile phase under damage of the seals of the fluid valves 106 to 109 is thereby avoided. More precisely, the fluid combining unit 136 between the fluid valves 106 to 109 and the combining position 148 has elongated inlet channels 144 to 147 whose common inner volume forms the compensating volume 112. Advantageously, the compensating volume 112 is at least 10 μL. Descriptively, the compensating volume 112 is formed by the leg length and the inner diameter of the inlet channels 144 to 147 in the substantially X-shaped structure according to FIG. 2. The compensating volume 112 is at least dimensioned as large as a maximum error volume which is pushed back by the high-pressure pump in operation.

[0100] FIG. 5 shows a fluid supply device 100 according to an exemplary embodiment of the invention.

[0101] FIG. 5 shows in particular the stiff plate-shaped body 142 which forms the fluid member 130 which is made of one piece or integrally formed. This fluid member 130 includes the manifold and the mixer. A valve block with the fluid valves 106 to 109 is illustrated in FIG. 6 with the reference sign 166.

[0102] FIG. 6 shows a fluid supply device 100 according to another exemplary embodiment of the invention.

[0103] In FIG. 6, four fluid component sources 156 to 159 are illustrated, wherein each of which is fluidically coupled with a respective supply conduit 102 to 105 for providing the respective fluid. The fluid component sources 156 to 159 may be configured as solvent containers. The above described fluid member 130 is connected downstream to the fluid valves 106 to 109. Furthermore, four elastic buffer units 110 are illustrated in FIG. 6, wherein each of which is fluidically coupled upstream of an assigned fluid valve 106 to 109 with an assigned one of the supply conduits 102 to 105. Each of the elastic buffer units 110 serves for buffering the fluid which flows through the respectively assigned one of the supply conduits 102 to 105. Descriptively, each of the elastic buffer units 110 serves as fluidic capacity or damper, to suppress pressure pulses or the like in the supply conduits 102 to 105. Furthermore, due to providing the elastic buffer units 110 with a variable or adjustable inner volume, a length of the supply conduits 102 to 105 up to the fluid component sources 156 to 159 may be kept short, which reduces delays with respect to the solvent supply and thus errors in the solvent composition.

[0104] In particular, it is possible to implement a tempering unit in the buffer units 110 which is configured for tempering (i.e. heating or cooling) the single solvent components. Alternatively or additionally, it is possible to implement a tempering unit which is configured for tempering (i.e. heating or cooling) the solvent mixture in the fluid member 130, in particular in its mixing unit 138. Thus, tempering the mobile phase and its solvent components, respectively, before and/or after mixing is possible. Also by this measure, the correctness of the composition of a mobile phase which is provided from the fluid conveying unit 20 may be improved.

[0105] Exemplary embodiments of buffer units 110 according to embodiments of the invention are illustrated in FIG. 7 to FIG. 9.

[0106] FIG. 7 shows a buffer unit 110 of a fluid supply device 100 according to an exemplary embodiment of the invention.

[0107] According to FIG. 7, the buffer unit 110 is configured as a member which may be fluidically connected by a fluid port 170 (for example a flange) at the side of the inlet and by a fluid port 172 (for example a further flange) at the side of the outlet to a supply conduit 102 to 105. A flow direction of the respective fluid through the buffer unit 110 is illustrated with arrows in FIG. 7. Furthermore, the buffer unit 110 comprises in its interior a variable buffer volume 113 which is delimited by a (for example stiff) housing portion 174 and an elastic compensating element 114. The elastic compensating element 114 serves for elastically compensating pressure fluctuations in the assigned supply conduit 102 to 105. Descriptively, in operation, the buffer unit 110 functions as a fluidic damping capacity, whose buffer volume 113 is enlarged in case of overpressure and reduced in case of underpressure.

[0108] Furthermore, in the buffer unit 110 according to FIG. 7, the elastic compensating element 114 is realized by an electroactive polymer. For example, the elastic compensating element 114 according to FIG. 7 may be configured as a membrane, preferably as silicone membrane. More precisely, the elastic compensating element 114 may form or include a sensor unit 116 of the buffer unit 110. This sensor unit 116 contains a sensor membrane for detecting a sensor information which is related to the fluid in the supply conduit 102 to 105. This sensor information may be a pressure or a flow rate of fluid in the supply conduit 102 to 105, for example. Depending on the pressure and/or the flow rate of the fluid, the sensor membrane is deflected more strongly or more weakly, which may be captured by measurement due to the realization of the sensor membrane from an electroactive polymer. Corresponding sensor data may be transferred to a control unit 70 which may capture the pressure and/or the flow rate of the fluid from the sensor data.

[0109] FIG. 8 shows a buffer unit 110 of a fluid supply device 100 according to another exemplary embodiment of the invention.

[0110] In addition to the members according to FIG. 7 (including the first elastic compensating element 114 shown in FIG. 7), the buffer unit 110 according to FIG. 8, as a part of its inner wall, has a further (or second) elastic compensating element 114 in the form of the membrane made of an electroactive polymer, such as silicone. The further elastic compensating element 114 is configured as an actor unit 118 of the buffer unit 110 for influencing an effect of the buffer unit 110 on the fluid. For this purpose, the further elastic compensating element 114 is actively controllable by providing electric control signals by the control unit 70. For example, the control unit 70 may apply such an electric voltage to the further elastic compensating element 114, that thereby the elasticity of the further elastic compensating element 114 and thus of the buffer unit 110 as a whole can be changed between a more rigid and a more flexible configuration, or also in a stepless or continuous manner. It is also possible to exert a force by the further elastic compensating element 114 on a fluid in the buffer volume 113 and/or in the supply conduit 102 to 105 which is fluidically coupled with it, for example in order to convey or drive this fluid.

[0111] Alternatively to the configuration according to FIG. 8, the (first) elastic compensating element 114 which is configured as a sensor membrane may also be omitted.

[0112] FIG. 9 shows a buffer unit 110 of a fluid supply device 100 according to yet another exemplary embodiment of the invention.

[0113] The embodiment according to FIG. 9 differs from the embodiment according to FIG. 7 by the fact that the buffer unit 110 at its inner wall comprises a tempering unit 120 for selectively heating and/or cooling the fluid in the buffer volume 113. For example, the tempering unit 120 may be controlled by the control unit 70 and may be configured as a Peltier element, for example.

[0114] FIG. 10 shows a fluid combining unit 136 with a subsequent mixing unit 138 for a (preferably integrally formed) fluid member 130 according to an exemplary embodiment of the invention.

[0115] The fluid combining unit 136 which is illustrated in FIG. 10 serves at first for splitting each fluid which is supplied at a respective one of the fluid inlets 132 to 135 into multiple respective partial channels 144a-d to 147a-d. The embodiment according to FIG. 10 concerns mixing the four fluids A, B, C and D. For the fluid A, it is illustrated how it is provided downstream of a fluid valve 106 at a fluid inlet 132. Downstream of the fluid inlets 132, the fluid A is split into the four partial channels 144a-d. Although not illustrated in detail in FIG. 10, correspondingly splitting for the fluids B, C and D into the partial channels 145a-d to 147a-d is performed. At each of the, in the illustrated embodiment four, combining positions 148, different partial channels 144a-d to 147a-d which are assigned to the fluids A, B, C and D are combined with each other. In more detail, at a first combining position 148, the fluid A from the partial channel 144a, the fluid B from the partial channel 145a, the fluid C from the partial channel 146a, and the fluid D from the partial channel 147a are combined with each other. In a corresponding manner, at a second combining position 148, the fluid A from the partial channel 144b, the fluid B from the partial channel 145b, the fluid C from the partial channel 146b, and the fluid D from the partial channel 147b are combined with each other, etc. In this way, at each of the combining positions 148, a respective combined flow of the different fluids A, B, C, and D is obtained. As illustrated in FIG. 10, the fluid combining unit 136 is further configured to supply the flows which are combined at the combining positions 148 to a mixing unit 138 for mixing. In the illustrated embodiment, mixing is already performed in a fluidic conduit network 138a between the combining positions 148 and a meander-mixer 138b which is illustrated as a block. It is also possible to configure the mixing unit 138 only as asymmetrical conduit network 138a or only as meander-mixer 138b.

[0116] Thus, according to FIG. 10, for a more robust combination, a combining position 148 may be parallelized into multiple cascades. If a combining position 148 is blocked, it is compensated by the other, still active combining positions 148, which thereby make combining the fluids A, B, C, and D redundant. This is advantageous in particular in the case of high salt loads. In the illustrated embodiment, a respective valve 106 to 109 with its outlet, for example a channel corresponding to the fluid A, is introduced into a distributing structure which leads to multiple similar combining positions 148. The channel structure is configured such that in T- or X-positions, respectively parallel fluid compositions are present. Thus, according to FIG. 10, combining in parallel in multiple similar combining positions 148 is enabled by a fluidic tree-structure, which is subsequently introduced into a mixing unit 138 (for example a mixing-meander-structure or a mixing unit according to FIG. 3). The illustrated embodiment corresponds to a mixing structure for a four-channel-multi gradient valve with four parallelized combining positions 148.

[0117] It should be noted that the term “comprise” does not exclude other elements and that the term “a” does not exclude a plurality. Also elements which are described in connection 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 protection of the claims.