FLUID PUMP HAVING LOW PRESSURE METERING AND HIGH

PRESSURE DELIVERING

BACKGROUND ART

[0001] The present invention relates to high-pressure fluid pumps.

[0002] Delivering under high pressure is useful, for example, in liquid chromatography to pump the mobile phase (specific composition of solvents) through the chromatographic system including the separation column. The pumping apparatus may form a part of a solvent delivery system which then comprises additional units for drawing in and mixing solvents.

[0003] Different approaches are known in the art for pumping the mobile phase through a chromatographic system. According pumping apparatuses usually require a pressure source and may comprise any possibility for blending different solvents, e.g. proportioning valves, followed by a mixing device and by filtering them through a certain amount of volume.

[0004] EP 0 309 596 B1 (by the same applicant), for example, shows a pumping apparatus comprising two pistons and two according pump chambers and control means coupled to drive means for adjusting the stroke length of the pistons.

[0005] A combination of a pump producing a pulsating stream of liquid such as a diaphragm pump and a pulse damper is disclosed in EP 0 115672 B1 (by the same applicant) to achieve delivering fluid against high pressure.

[0006] US 4,003,679 (by the same applicant) discloses a pumping system provided in which a low pressure metering pump injects fluid charges into a high pressure pump which in turn operates into a high pressure load.

[0007] US 4,599,049 (by the same applicant) discloses a high pressure meter pump system with improved accuracy by subdividing a large meter pump capacity into metered subvolume charges which are incrementally delivered to a high pressure

slave pump.

[0008] Another system is shown in the US 4,714,545 (by the same applicant), wherein a plurality of fluid solutions are connected to an input of a pump system having at least two displacement chambers.

DISCLOSURE OF THE INVENTION

[0009] It is an object of the invention to provide an improved delivery of fluid. The object is solved by the independent claims. Preferred embodiments are shown by the dependent claims.

[0010] According to embodiments of the present invention, a pumping apparatus adapted for metering at least two different fluids, for example liquids, and for delivering the metered fluids against pressure, for example against high pressure at which compressibility of the fluid becomes noticeable, is suggested.

[0011] The pumping apparatus comprises a plurality of metering devices adapted for metering a plurality of different fluids. Each metering device comprises an inlet and an outlet, wherein the outlets of the metering devices all are coupled to an inlet of a booster device of the pumping apparatus. In other words, the metering devices can be connected in parallel orsi<3e-by-side. Consequently, different flows, for example flows of different fluids, can flow through the metering devices in parallel, wherein all flows of said different fluids lead into one common flow leading into the booster device.

[0012] Advantageously, the different fluids can be blended by transporting them to the inlet of the booster device. The outlet of the booster device is coupled to the inlet of a damping device. The booster device and the damping device are connected in series, wherein the booster device can be adapted for increasing the pressure of the fluids metered by the plurality of metering devices to said high pressure. Consequently, the different fluids can be blended precisely under low-pressure condition before reaching the inlet of the booster device of the pumping apparatus, being compressed within the booster device, and finally being provided at the outlet of the damping device under high-pressure condition. The damping device can be designed and operated to compensate any occurring flow and thus pressure

fluctuation of the fluids metered by the metering devices and compressed by the booster device. This makes it possible to deliver a stream of fluid at higher pressures, relatively low flow rates, and fewer pulsations.

[0013] The booster device and the damping device can be synchronized with each other and with the metering devices such that the damping device still delivers flow while the booster device gets refilled. The metering devices are reloaded while the booster device is delivering. Consequently, the pumping apparatus can generate a ripple-free flow of precisely dosed composition under said high pressure.

[0014] Advantageously, the plurality of metering devices are adapted for simultaneous dosing of composition combined with a serial configuration of the booster device and the damping device employed for generating the continuous flow under said high pressure. In a minimum configuration comprising two metering devices, the pumping apparatus needs about the same hardware as a dual isocratic serial pump, but achieves composition independent of system backpressure.

[0015] Advantageously, miniaturized chromatographic systems, for example, which generally need lower flow rates, higher pressures, and refined mixing ratios, can be supplied with fluid by such a pumping apparatus. Besides this, the mobile phase can be pumped through said chromatographic systems with an increased accuracy of system parameters like flow rate and pressure. Advantageously, said improved performance of the pumping apparatus enables enhancing the performance of coupled chromatographic systems. Due to the improved pumping apparatus, such coupled systems can comprise one or more of the following features for enhancing the performance: Smaller size of packing material, smaller id columns, faster linear speed of solutions during separation, faster compositional gradients, and longer separations beds. Summarizing, the total amount of liquid in use can be reduced without seriously endangering the quality of the separation process.

[0016] For chromatographic analysis, for example, a flow rate of fluid can be delivered to the column by the pumping apparatus being adjustable across a wide range of flow rates. Besides this, the pumping apparatus permits the generation of mixtures of solvents and changing the compositional ratio of the various solvents of the

mixture in the course of time (gradient operation). Such versatility of the pumping apparatus allows optimizing the analysis conditions for the specific sample to be chromatographically separated.

[0017] Advantageously, the flow rate can be adjustable or selectable and can be - once selected - kept substantially constant by the booster devices. Thus reducing fluctuation of the flow rate through the separation column leading to variations in the retention time and peak width of the examined sample compounds so that the areas of the chromatographic peaks produced by a detector connected to the outlet of the column, for example, an absorption detector, a fluorescence detector, or a refractive index detector, would vary. Since the peak areas are representative for the concentration of the chromatographically separated sample substances, preventing or reducing fluctuations in the flow rate can advantageously improve the accuracy and the reproducibility of quantitative measurements.

[0018] Embodiments may comprise one or more of the following. Advantageously, the metering devices can deliver fluid synchronously to the booster device. In embodiments, the damping device can realize an active pulse damper. An active pulse damper can comprise at least one correcting element for influencing at least one parameter, for example the pressure within the damper. Advantageously, the damping device can actively stabilize the output pressure of the pumping apparatus. This makes it possible that the metering devices produce a pulsating stream of exactly blended fluid at low pressure into the booster device and that the booster device produces an also pulsating stream of said blended fluid at high pressure without abandoning the aim of a ripple-free output stream of blended fluid under high pressure.

[0019] The metering devices can concurrently produce a plurality of exactly metered streams of fluid into the inlet of the booster device. Advantageously, the streams can be blended homogenously just by transporting them into a common connection conduit to the inlet of the booster device. While the metering devices draw up fresh fluid the booster device compresses the composition to system pressure and takes over conveying the high-pressure stream from the damping device. In this period the damping gets refilled too.

[0020] Embodiments may comprise one or more of the following. The outputs of the metering devices can be coupled to the inlet of the booster device via a mixing device. The mixing device can comprise a certain volume for filtering the streams of the metering devices. The mixing device comprises one inlet for each of the metering devices and one common outlet coupled to the inlet of the booster device. The apparatus can comprise according connection conduits between the outlets and inlets of the devices, one for each inlet of the mixing device and the outlet of the according metering device, one between the outlet of the mixing device and the inlet of the booster device, and one between the outlet of the booster device and the inlet of the damping device.

[0021] Possibly, the mixing device comprises a certain volume forfiltering or mixing the streams produced by the metering devices. The metering devices are adapted for delivering fluid concurrently to the inlet of the mixing device.

[0022] Advantageously, the mixing device can be realized by a simple branch tee - or by a multi-branch connector having a plurality of inlets and one common outlet when more than two metering devices are employed - for avoiding any dead volume. The different fluids can be mixed exactly and simply just by delivering or metering them concurrently into the connection conduit between the outlet of the branch tee and the inlet of the booster device. This reduces any dead volume causing undesired side effects affecting the quality of the flow rate and/or the output pressure to a minimum.

The different fluids can be blended at a relative low pressure level. This way decoupling composition blending from the system backpressure, which makes it possible to reduce any side effects occurring while blending different fluids affecting the mixing ratio or the system pressure to a negligibly small value. Besides this, for reducing any dead volume to a minimum, the length of said connection conduits can be reduced to a minimum. For example, the branch tee can be integrated in the booster device.

[0023] Advantageously, the volume of the booster device can be used for filtering the inflowing blend of different fluids. By this, the booster device additionally realizes a mixing device resulting in a highly homogenous blend of the different fluids deliverable

by the pumping apparatus.

[0024] Embodiments may comprise one or more of the following. The pumping apparatus is operated substantially at three different pressures: A sucking pressure, a mixing pressure, and an output pressure. The metering devices each are adapted for letting in fluid at the sucking pressure and for delivering fluid, in particular to the mixing device, at the mixing pressure. The sucking pressure, for example, may be below ambient pressure or below the pressure within containers coupled to the metering devices and comprising the solvents. The mixing pressure is relatively low, for example, between 10 mbar and where compressibility becomes noticeable. The booster device is adapted for letting in fluid at the mixing pressure and for delivering fluid at the output pressure to the inlet of the damping device. Consequently, the booster device is adapted for increasing the system pressure from the relatively low mixing pressure to the high output pressure. The mixing device as well as the booster device are operated at both, the low mixing pressure and the high output pressure. Advantageously, the pressure can be increased after blending the different fluids, thus having no influence on the composition of compressible fluids. The damping device is adapted for letting in and for letting out fluid at the high output pressure. Advantageously, the damping device can behave like an active damping device stabilizing the output pressure at a value resulting from current flow rate and fluid composition, ranging from 20 bar up to 2000 bar.

[0025] Embodiments may comprise one or more of the following. The metering devices and the booster devices each comprise a piston for reciprocation in an according pump or booster chamber. Accordingly, the pumping apparatus comprises a valve arrangement with a plurality of valves adapted for allowing the flow of fluid into the inlets of the metering devices and the booster devices respectively, the according pump or booster chambers, and for inhibiting the flow in the opposite direction. The valve arrangement can comprise one or more flow check valves, on-off valves, and/or flow control valves or any other valves suitable for this purpose. Preferably, the pump chambers or rather the inlets of the metering devices are each coupled downstream to inlet valves adapted for allowing the flow of fluid into the pump chambers of the metering devices and for inhibiting the flow in the opposite direction.

[0026] Accordingly, the inlets of the mixing device, in particular the branch tee, are coupled to inlet valves adapted for allowing the flow of fluid into the mixing device and for inhibiting the flow in the opposite direction. In this configuration, the inlet of the booster device is just coupled to the outlet of the mixing device. Alternatively or additionally, the connection conduit between the mixing device and the booster device can comprise an according inlet valve.

[0027] Embodiments may comprise one or more of the following. Advantageously, the pumping apparatus comprises a control unit. The control unit controls at least one controllable feature such as the metering devices, the booster devices, and the valves of the valve arrangement. For this purpose, the control unit can communicate with the different elements in an open or closed loop mode.

[0028] For realizing a negative feedback closed loop controller, the embodiments of the pumping apparatus can comprise one or more different sensors, such as a pressure sensorfor measuring the pressure within any of the conduits or chambers of the pumping apparatus, a flow sensor for measuring the flow rate within any of the conduits of the pumping apparatus, a position sensor for measuring the position of any of the pistons of the metering or booster devices, or any other suitable sensor using any suited method of measuring system variables needed by the controller. Consequently, the control unit can realize, for example, a pressure controller, a position controller, and/or a flow controller for controlling at least one of the following pressures, the sucking pressure, the mixing pressure, and the output pressure, the switching status of any one of the valves, the position of any one of the pistons of the metering devices, the position of any one of the pistons of the booster devices, and/or the flow within any one of the connection conduits.

[0029] Advantageously, the control unit can control the damping device, in particular the movement of the piston of the damping device within the damping chamber of the damping device for realizing an active pulse damping unit in a manner that the output pressure is substantially stabilized. Advantageously, this enables a smother changeover of composed fluid from the metering devices into the booster device and from the booster device into the damping device. In other embodiments, the

mixing pressure can be controlled accordingly. In such constant pressure mode for the mixing pressure, the volume contraction can be measured during the time when both metering devices dispense their respective volume, for example by measuring the position of the pistons of the metering devices and the booster device. Depending on the timing of dispense/reload cycles, the mixing volume can be adapted to achieve best performance at a given flow rate by running the pistons at variable stroke and frequency when the volume of the booster chamber of the booster device is used for filtering or mixing the inflowing fluid. A method of running pistons at variable stroke and frequency is disclosed in the EP 0 309 596 B1, which is incorporated herein by reference. Advantageously, the inlets and the outlets of the booster devices are positioned at the booster chambers of the booster devices in a manner that a first in first out (FIFO) concept is realized. Consequently, any fluid streaming into the booster chambers of the booster devices through the respective inlet is flowing out first as well. This makes it possible to store a gradient in the pump chamber of the damping device which is then dispensed to the system as a homogenous blend.

[0030] Embodiments may comprise one or more of the following. The pistons of the metering devices can run in synchronous fashion when individual flow rates are at comparable levels. But when flow rates differ, say e.g. 10/1 , the slower moving piston may just start/stop dispensing until its volume is at a minimum limit. In other words, the slower moving piston stops for each half cycle of sucking fresh fluid. The proportion of the amplitudes of the synchronous strokes of the pistons of the metering devices is substantially equal to the mixing ratio, if side effects caused by the compressibility of the fluids are not taken into consideration.

[0031] Embodiments may comprise one or more of the following. For realizing an open loop controller, the control unit can comprise data of the fluids to be mixed, in particular the compressibility, used for calculating and controlling the optimal movement of the pistons of the pumping apparatus for realizing the substantial stabilized output pressure. The data can comprise, for example, one or more of the following parameters: The compressibility of each fluid as a function of pressure and temperature, the compressibility of the blend as a function of pressure and temperature, the viscosity of the fluids and of the blend as a function of pressure and

temperature, and the mixing volume as a function of mixing ratio, mixed fluids, temperature, and pressure. The specific volume of the fluids after blending shall be understood herein, for example, as the mixing volume. Of special interest can be the loss or gain of volume during or after blending.

[0032] By using the data above and calculating said loss or gain of volume during or after blending, any retroactive effect to the desired output pressure can be compensated by the control unit. Consequently, the control unit can calculate the optimal movement and timing of the pistons of the metering devices and the booster devices for realizing the open loop controller or, if desired, a closed loop controller. For each fluid, the control unit can be fed with the corresponding parameters. Possibly, the control unit can realize an adaptive system wherein the control unit measures the parameters needed during an initial phase before operating the pumping apparatus. Especially advantageously, the control unit can realize a mixture of the closed and open loop modes.

[0033] Recapitulating, the control unit can realize a drive control for all metering devices and booster devices of the pumping apparatus in a manner that the output pressure is substantially stabilized and a stream of a homogenous blend with an exactly determined mixing ratio is generated.

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[0034] According to other embodiments of the present invention, a fluid separation system comprising a fluid delivery system comprising a pumping apparatus as described above and a separation device for separating components of the fluid delivered by the fluid delivery system is suggested. Advantageously, the pumping apparatus can produce an exact ripple-free flow of fluid for optimizing the performance of the fluid separation system.

[0035] Further embodiments of the present invention relate to a method of delivering fluid at high pressure at which compressibility of the fluid becomes noticeable. In a first step, a plurality of different fluids is metered by a plurality of metering devices. Subsequently, the fluids are received from the plurality of metering devices upstream by a booster device and a damping device. Finally, the pressure of the metered fluids is increased within the booster device to said high pressure.

Advantageously, the fluids can be blended at a relative low pressure. In embodiments, a pumping apparatus as described above is employed for executing the method. Additionally, the different fluids can be mixed before the booster device receives them. Besides this, the pressure of the mixed fluid can be increased within the booster device and delivered at said high pressure to the damping device. Advantageously, the damping device does not have to increase the pressure and can be employed for stabilizing the output pressure, for example actively stabilizing the output pressure. As an additional step, fluctuations of the mixed fluid can be compensated by the damping device.

[0036] Embodiments of the invention can be partly or entirely embodied or supported by one or more suitable software programs, which can be stored on or otherwise provided by any kind of data carrier, and which might be executed in or by any suitable data processing unit. Software programs are preferably applied for controlling the steps of the method as described above, e.g., by using a control unit comprising the software programs. Besides this, the control unit can comprise software programs for controlling set points of the pumping apparatus.

BRIEF DESCRIPTION OF DRAWINGS

[0037] 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.

[0038] Fig. 1 shows a pumping apparatus with two metering devices and two booster devices connected in series, and

[0039] Fig. 2 shows a schematic view of a fluid separation system with a fluid delivery system comprising a pumping apparatus.

[0040] Fig. 1 shows a pumping apparatus 1 with a first metering device 3, a second metering device 5, a booster device 7, and a damping device 9. The devices 3, 5, 7, and 9 can be controlled by a control unit 11. The first metering device 3 comprises a

first piston 13 for reciprocation in a first pump chamber 15, the second metering device 5 comprises a second piston 17 for reciprocation in a second pump chamber 19, the booster device 7 comprises a third piston 21 for reciprocation in a booster chamber 23, and the damping device 9 comprises a fourth piston 25 for reciprocation in a damping chamber 27.

[0041] The pistons 13, 17, 21 , and 25 each are coupled to a screw link actuator 29 driven by a motor 31. The screw link actuators 29 are coupled via balls 33 to the according devices 3, 5, 7, and 9. The screw link actuators 29, the motors 31 , and the balls 33 are component parts of drives 35 for actuating the devices 3, 5, 7, and 9 respectively the pistons 13, 17, 21, and 25. Drives as the drives 35 for actuating pistons for reciprocation in pump chambers are known in the art and therefore not describer in detail in this application.

[0042] The outer diameters of the pistons 13, 17, 21 , and 25 are smaller than the inner diameters of bores 37 of the pump chambers 15 and 19 respectively of bores 39 of the booster chambers 23 and 27. This makes it possible that fluid can flow into the gaps between the pistons 13, 17, 21, and 25 and the inner surface of the according bores 37 respectively 39.

[0043] Each of the devices 3, 5, 7, and 9 comprises an inlet 41 and an outlet 43. Advantageously, the inlets 41 of the devices 3, 5, 7 and 9 are coupled to an end off the bores 37, 39 located upstream of the upstream inflection point of the pistons 13, 17, 21, and 25, wherein the outlets 43 of the devices 3, 5, 7 and 9 are coupled to the opposite end of the bores 37, 39 located downstream of the downstream inflection point of the pistons 13, 17, 21, and 25. By this, fluid sucked firstly into any one of the chambers 15, 19, 23, or 27 can be dispensed firstly as well. By this, a first in first out principle can be realized.

[0044] The pumping apparatus 1 comprises a valve arrangement with a plurality of valves 45 to 53. The valve arrangement is adapted for allowing the flow of fluid into the inlets 41 of the devices 3 to 9 respectively the chambers 15, 19, 23, and 27, and for inhibiting the flow in the opposite direction. In embodiments, the valve arrangement can comprise one ore more flow check valves, on-off valves, and/or flow control valves

or any other valves suitable for said purpose. In embodiments, the chambers 15, 19, 23, and 27 each are coupled downstream to at least one valve of the plurality of valves 45 to 53 of the valve arrangement.

[0045] The first pump chamber 15 of the first metering device 3 is coupled downstream to a first inlet valve 45 via the inlet 41 of the first metering device 3 and a first inlet connection conduit 55. The second pump chamber 19 of the second metering device 5 is coupled downstream to a second inlet valve 47 via the inlet 41 of the second metering device 5 and a second inlet connection conduit 57. In embodiments, the inlet valves 45 and 47 of the metering devices 3 and 5 are realized as flow check valves. In other embodiments, as shown in Fig. 1, the inlet valves 45 and 47 can comprise a valve controller 59, for example, controlled by the control unit 11. The valve controller 59 together with the control unit 11 can exactly adjust the flow within the connection conduits 55 and 57 and accordingly within the chambers 15 and 19 of the metering devices 3 and 5. The valve controllers 59 can open the valves 45 and 47 while sucking fresh fluid and can close them while delivering the fluid through the outlets 43 of the metering devices 3 and 5.

[0046] The first pump chamber 15 of the first metering device 3 is coupled upstream to a mixing device 61 via the outlet 43 of the first metering device 3 and a third connection conduit 63 comprising a first mixing inlet valve 49. The second pump chamber 19 of the second metering device 5 is coupled upstream to the mixing device 61 via the outlet 43 of the second metering device 5 and a fourth connection conduit 65 comprising a second mixing inlet valve 51. The mixing inlet valves 49 and 51 are positioned within the connection conduits 63 and 65 close to the mixing device 61. In embodiments, the position of the mixing inlet valves 49 and 51 within the connection conduit 63 and 65 may vary. For example, the mixing inlet valves 49 and 51 can be positioned as close as possible to the metering devices 3 and 5.

[0047] The mixing device 61 comprises a first mixing inlet 67 coupled to the third connection conduit and a second mixing inlet coupled to the fourth connection conduit.

The mixing device 61 comprises one inlet 67, 69 per metering device 3, 5. In embodiments, the pumping apparatus 1 can comprise more or less than two metering

devices and respectively the mixing device 61 can comprise more than two inlets 67 and 69. All mixing inlets 67 and 69 of the mixing device 61 lead into one common fifth connection conduit 71. The fifth connection conduit 71 is coupled between a mixing outlet 73 of the mixing device 61 and the inlet 41 of the booster device 7.

[0048] The mixing device 61 can comprise a certain volume for filtering and blending the fluid delivered by the metering devices 3 and 5. Advantageously, the mixing device 61 can comprise a simple branch tee as indicated with dotted lines 75. Advantageously, the fluids delivered by the metering devices 3 and 5 can be blended simply by delivering them, for example, concurrently through the branch tee - as indicated with the dotted lines 75 - of the mixing device 61 of the pumping apparatus 1 into the fifth connection conduit via the mixing outlet 73 of the mixing device 61.

[0049] The booster chamber 23 is coupled upstream to the damping chamber 27 via the outlet 43 of the booster device 7, a sixth connection conduit 77 comprising a booster outlet valve 53, and the inlet 41 of the damping device 9. The damping chamber 23 of the damping device 9 is coupled to an outlet conduit 79 via the outlet 43 of the damping device 9. The outlet conduit 79 can be coupled to a system, for example a liquid chromatographic system, to be fed with fluid by the pumping apparatus 1.

[0050] The pistons 13 and 17 or the metering devices 3 and 5 are moved in phase for delivering fluid concurrently into the booster chamber 23 of the booster device 7 via the connection conduits 63, 65, 71 , and the mixing device 61. The velocities of the single pistons 13 and 17 of the metering devices 3 and 5 can determine the mixing ratio of the fluid delivered into the booster chamber 23.

[0051] After delivering the fluid with the desired mixing ratio, said fluid can be compressed within the booster chamber 23 by the third piston 21 and delivered via the sixth connection conduit 77 into the damping chamber 27 of the damping device 9. The pumping apparatus 1 comprises substantially three pressure levels. For example, fresh fluid can be sucked into the pump chambers 15 and 17 by the metering devices 3 and

5 at a pressure level lower than the ambient pressure, a first sucking pressure. For transporting the fluid into the booster chamber 23, said fluid can be compressed to a

second higher mixing pressure. Finally, the booster device 7 can increase the pressure of said fluid up to a third pressure, the desired output pressure of the pumping apparatus 1.

[0052] Fig. 2 shows a schematic view of a fluid separation system 95 with a fluid delivery system 97 comprising the pumping apparatus 1 and a separation device 99 for separating components of the fluid delivered by the fluid delivery system 97. The fluid separation system 95 can comprise a detecting device 101 or a coupling 103 to the detection device 101. The detection device 101 can be employed for detecting components of the fluid separated by the separation device 99. Besides this, the fluid separation system 95 can be connected to a not shown apparatus, for example a mass spectrograph, for analyzing the fluid, for example liquid, via a connection conduit 105. The separation device 99 can be realized, for example, as a high performance liquid chromatography chip. The pumping apparatus, for example coupled to the control unit 11, 1 can deliver a ripple-free stream of a blend of different liquids, for example a gradient of two solvents, to the separation device 99, for example the high performance liquid chromatography chip.

[0053] In the following different phases of operation of the pumping apparatus 1 are described in detail by referring to the different pressure levels and to Fig. 1:

[0054] In a first phase, fresh fluid is sucked by the metering devices 3 and 5. In this first phase, the pistons 13 and 17 of the metering devices 3 and 5 are moved - in direction of the Fig. 1 - downwards. This increases the volume within the pump chambers 15 and 19, whereas fresh fluid can flow into the pump chambers 15 and 19 through the connection conduits 55 and 57. In the first phase, the valves 45 and 47 are opened and the mixing inlet valves 49 and 51 are closed. In this phase, the pumping apparatus 1 is operated downstream to the mixing inlet valves 49 and 51 at the lowest pressure level, at the sucking pressure.

[0055] In a second phase, the inlet valves 45 and 47 are closed and the pressure upstream of the mixing inlet valves 49 and 51 is increased up to a second higher pressure level, the mixing pressure, by moving the pistons 13 and 17 of the metering devices 3 and 5 - in direction of the Fig. 1 - upwards. Due to the compressibility of the

fluids within the metering devices 3 and 5 and possibly existing elasticity of fluid conducting component parts of the pumping apparatus 1 , the mixing inlet valves 67 and 69 stay closed although the pistons 13 and 17 of the metering devices 3 and 5 a re moving upwards. Therefore, no fluid is delivered from the metering devices to the mixing device in the second phase. Advantageously, the second phase can be reduced to a minimum by choosing a relatively low mixing pressure. At such a low mixing pressure any side effects caused by the compressibility of the different fluids to be blended within the mixing device 61 can be reduced to a minimum.

[0056] In a third phase, the metering devices 3 and 5 deliver fluid concurrently into the booster chamber 23 of the booster device 7. In this phase, the damping device 9 still delivers fluid into the outlet conduit 79. The third phase equals the phase of a serial dual isocratic piston pump sucking fresh fluid. In difference, the fresh fluid is transported actively into the booster chamber 23 of the booster device at the mixing pressure by the metering devices 3 and 5. For this purpose, the movements of the pistons 13, 17, and 21 of the metering devices 3 and 5 and the booster device 7 have to be synchronized in a manner that the pressure between the booster outlet valve 53 and the inlet valves 45 and 47 of the pumping apparatus 1 is stabilized at the mixing pressure. Volume contraction of the fluid while blending can be corrected in this phase.

[0057] In a fourth phase, after filling the booster chamber 23 with blended fluid, the mixing inlet valves 49 and 51 are closed and the fluid within the chambers 15 and 19 of the metering devices 3 and 5 is decompressed until the sucking pressure is reached and consequently the inlet valves 45 and 47 open by moving the pistons 13 and 17 of the metering devices 3 and 5 - in direction of the Fig. 1 - downwards. At the same time, the, booster device 7 starts compressing the blended fluid up to the high output pressure and delivering the blended fluid into the damping chamber 27 as described above.

[0058] The part-cycle of the booster device 7 of compressing, delivering, and decompressing the mixed or blended fluid has to be stopped at the moment when the metering devices 3 and 5 are ready again (see phase three) for delivering freshly sucked fluid at the mixing pressure into the booster chamber 23 via the mixing device

61. At the same moment, the pressure within the pump chambers 15 and 19, within the mixing device, and within the booster chamber 23 has to be reached the mixing pressure.

[0059] The booster outlet valve 53 closes at the moment when the pressure within the booster chamber 23 starts dropping from the output pressure to the mixing pressure. Consequently, starting from this moment, the damping device 9 has to deliver the fluid alone and the movement of the fourth piston 25 of the damping device 9 has to be changed or reversed for avoiding any pulsation or any pressure failure in the outlet connection conduit 79 of the pumping apparatus 1.

[0060] In the first, second, and fourth phase, the system upstream of the mixing inlet valves 49 and 51 is operated at a pressure level between the mixing pressure and the high output pressure. More precisely, the pressure upstream of the booster outlet valve 53 is always kept stable at the high output pressure by the damping device 9. For this purpose, the damping device 9 can be coupled to a pressures sensor 81 for realizing, for example, a pressure controller 83 for the output pressure of the pumping apparatus 1. The pressure controller 83 can be implemented in the control unit 11. The booster device 7 can comprise an according booster pressure sensor.

[0061] ^ During the phases 1, 2, and 4, the booster device 7 delivers fluid into the damping chamber 27 of the damping device 9 by moving the third piston 21 of the booster device within the booster chamber— in direction of the Fig. 1 — upwards. After compressing the blended fluid within the booster chamber 23, the booster outlet valve 53 opens and the fourth piston 25 of the damping device 9 can change its direction of movement - in direction of the Fig. 1 - downwards. The booster device 7 and the damping device 9 realize a serial dual isocratic piston pump for delivering a constant flow of fluid under high pressure.

[0062] For realizing a drive control for the described phases one to four of the pumping apparatus 1 and for delivering a ripple free stream of blended fluid into the outlet conduit 79 of the pumping apparatus 1 , the pumping apparatus 1 can be coupled with the control unit 11 via a plurality of control connections 85. The control unit 11 can realize, for example, the pressure controller 83 for the output pressure of the pumping

apparatus 1 , a position controller 87 for the drives 35 of the devices 3 to 9, or a flow controller 89 for controlling the flow rates within the connection conduits 55, 57, 63, 65, 71 , 77 and 79. For this purpose, the pumping apparatus 1 can additionally comprise not shown pressures sensors, flow sensors, and/or position sensors.

[0063] Besides this, in embodiments, the control unit 9 can communicate with encoders 91 coupled to the motors 31 of the drives 35. Besides this, each of the drives 35 of the pumping apparatus 1 can comprise one drive controller 93 connected via at least one of the control connections 85 to the control unit 11. The control unit 11 interprets all data delivered by the pumping apparatus 1 for realizing a highly sophisticated drive control for the pistons 13, 17, 21, and 25. For this purpose, the drive control realized by the control unit 11 can store, calculate, and/or measure relevant parameters within the connection conduits within the pumping apparatus 1 , for example the compressibility or viscosity of the fluids transported through the pumping apparatus 1. The control unit 11 can realize one or more open and/or closed loop controllers.

[0064] At the high pressures encountered, for example, in high performance liquid chromatography, compressibility of the solvents becomes noticeable resulting in an additional source of pulsation. The reason is that during each compressing cycle of the booster device 7, the third piston 21 of the booster device 7 has to move a certain path to compress the fluid to its final output pressure before actual delivery to the damping device 9 starts. Advantageously, the damping device 9 can compensate this effect. Besides this, side effects caused by the change of the mixing volume or the viscosity of the different fluids while blending them are negligibly small because of blending at the relative low mixing pressure. This results in a ripple-free and constant flow under high pressure at the outlet 43 of the damping device 9 of the pumping apparatus 1.

[0065] Recapitulating, the control unit 11 controls the movement of all pistons 13, 17, 21 , and 25 for guaranteeing an optimal handshake or better a smooth changeover of the metering devices 3 and 5 with the booster devices 7 and 9 and of the booster device 7 with the damping device 9 for ensuring a ripple-free and constant stream of fluid delivered by the pumping apparatus 1. On account of the drive control by the

control unit 11 the damping device 9 can act as an active damping device.

[0066] In the following a method of delivering fluid at high pressure at which compressibility of the fluid becomes noticeable, for example by using a pumping apparatus of Fig. 1 or a fluid separation system of Fig. 2, is described by referring to the figures.

In a first step, a plurality of different fluids is metered with the plurality of metering devices 3, 5. Subsequently, the fluids are received from the plurality of metering devices 3, 5, for example by the booster device 7 via the mixing device 61. The fluids can be transported from the plurality of metering devices 3, 5 into the mixing device 61 , and from there into the booster device 7. Finally, the pressure of the metered fluids is increased within the booster device 7 to said high pressure and can be delivered at said high pressure to the damping device 9. The fluids can be mixed, for example within the mixing device 61 and/or within the booster chamber 23 of the booster device 7, for example by metering them concurrently. As an additional step, fluctuations of the mixed fluid can be compensated by the damping device 9. During executing the method, a control unit 11, for example comprising suited software programs or routines, can control the steps as described above.

[0067] The pumping apparatus can be coupled to a fluid separation system for analyzing and or separating fluid, more specifically, for executing at least one microfluidic process, for example a liquid chromatographic process, for example a high performance liquid chromatographic process (HPLC). For analyzing a fluid, for example a liquid, or rather one or more components within the fluid or liquid, the coupled system can comprise a detection area, such as an optical detection area and/or an electrical detection area being arranged close to a flow path within the system. Alternatively, the fluid separation system can be coupled to a detection area or a detecting apparatus such as a mass spectrograph. The fluid separation system can be realized as a chromatographic system (LC), a high performance fluid chromatographic (HPLC) system, an HPLC arrangement comprising a chip and an mass spectrograph (MS), a high throughput LC/MS system, a purification system, micro fraction collection/spotting system, a system adapted for identifying proteins, a

system comprising a GPC/SEC column, a nanoflow LC system, and/or a multidimensional LC system adapted for separation of protein digests, or alike. Besides this, the pumping apparatus can be a component part of a laboratory arrangement.

[0068] It is to be understood, that this invention is not limited to the particular component parts of the devices described or to process steps of the methods described as such devices and methods may vary. It is also to be understood, that different features as described in different embodiments, for example illustrated with different Fig., may be combined to new embodiments. It is finally to be understood, that the terminology used herein is for the purposes of describing particular embodiments only and it is not intended to be limiting. It must be noted, that as used in the specification and the appended claims, the singular forms of "a", "an", and "the" include plural referents until the context clearly dictates otherwise. Thus, for example, the reference to "a damping device" or "an inlet valve" includes two or more such functional elements.