US20160153439A1

US20160153439A1 - Method for pumping fluid in a fluid separation device and related devices and systems

Info

Publication number: US20160153439A1
Application number: US14/959,892
Authority: US
Inventors: Klaus Witt; Konstantin Shoykhet
Original assignee: Agilent Technologies Inc
Current assignee: Agilent Technologies Inc
Priority date: 2011-05-09
Filing date: 2015-12-04
Publication date: 2016-06-02
Also published as: GB2490673B; US20120285558A1; GB2490673A; GB201107658D0; CN202811312U

Abstract

In a fluid separation device, fluid supplied to a fluid inlet conduit at an inlet flow rate is split such that a first part of the fluid flows into a first outlet conduit and into a pump at a first flow rate, and a second part of the fluid flows from the fluid inlet conduit into a second outlet conduit at a second flow rate. The second flow rate is controlled by controlling the pump such that, regardless of inlet pressure in the fluid inlet conduit, the first part of the fluid is continuously conducted away from the fluid inlet conduit at a defined value of the first flow rate. The second flow rate is defined based on the defined value of the first flow rate.

Description

RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No. 13/441,021, filed Apr. 6, 2012, which claims priority from UK Patent Application No. GB 1107658.5, filed May 9, 2011, which are incorporated herein by reference in their entireties.

TECHNICAL FIELD

The present invention relates to a fluid pump, a flow splitter, a sample separation device, and methods of handling fluids.

BACKGROUND

US 2008/0022765 discloses a liquid chromatography device, particularly a flow meter with a metering device for intaking and metering an externally given volume of a fluid, and with a control unit for controlling the fluid intake of the metering device for determining a flow rate of the fluid.
In liquid chromatography, a fluidic sample and an eluent (liquid mobile phase) may be pumped through conduits and a column in which separation of sample components takes place. The column may comprise a material which is capable of separating different components of the fluidic analyte. Such a packing 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) by conduits. The composition of the mobile phase can be adjusted by composing the mobile phase from different fluidic components with variable contributions. Under undesired circumstances, the flow and sometimes also the composition of the delivered mobile phase may be altered or disturbed, which may deteriorate proper operation of the sample separation device.
In HPLC technology, a desired flow through a separation column may be significantly larger than a desired flow through a mass spectroscopy detector which is used for analyzing separated components of the fluid. On the one hand, reducing the flow through the separation column to meet the requirements of mass spectroscopy may result in artifacts in the detection peaks such as peak broadening. On the other hand, increasing the flow through the mass spectroscopy device to meet the requirements of the separation column is not easily possible as well. Thus, proper operation of a fluid separation device may still be difficult particularly when a mass spectroscopy device shall be implemented for analysis purposes.
Therefore, there is a need to efficiently manage flow streams for enabling improved performance of fluid separation.

SUMMARY

To address the foregoing problems, in whole or in part, and/or other problems that may have been observed by persons skilled in the art, the present disclosure provides methods, processes, systems, apparatus, instruments, and/or devices, as described by way of example in implementations set forth below.
According to an exemplary embodiment of the present invention, a fluid pump for a fluid separation device for separating a fluid is provided, wherein the fluid pump comprises a fluid inlet being supplyable with fluid with an inlet pressure, and a fluid conducting mechanism configured for conducting the fluid supplied to the fluid inlet towards a connected fluidic path, wherein the fluid conducting mechanism is controllable so that, regardless of a value of the inlet pressure, the fluid is continuously conducted away from the fluid inlet with a definable (or defined) flow rate. It has to be understood that this can be accomplished as an active pumping action, although in reverse direction, in contrast to passive modes, which modulate the restriction of a hydraulic path in order to control the rate of flow.
According to another exemplary embodiment, a flow splitter for a fluid separation device for separating a fluid is provided, wherein the flow splitter comprises a fluid inlet conduit by which fluid is supplyable, a first fluid outlet conduit and a second fluid outlet conduit both being in fluid communication with the fluid inlet conduit so that at least a part of fluid supplied by the fluid inlet conduit is split between the first fluid outlet conduit and the second fluid outlet conduit, wherein the flow splitter is configured so that the portion of the fluid supplied through the fluid inlet conduit is continuously conducted away from the junction and thus from the first fluid outlet conduit with a definable (or defined) flow rate. In other terms, a flow subtraction unit can be provided.
According to still another exemplary embodiment, a fluid separation device for separating a fluid is provided, wherein the fluid separation device comprises a fluid drive, particularly a pumping system, configured to drive the fluid through the fluid separation device, a separation unit, particularly a chromatographic column, configured for separating the fluid. Additionally, a fluid pump having the above-mentioned features and/or a flow splitter having the above-mentioned features may be provided in the fluid separation device. The fluid pump and/or the flow splitter may be arranged for example upstream of the separation unit to operate the pump under its optimal conditions while the separation unit is operated best at a smaller flow rate, or downstream from the separation unit to operate a downstream device, such as detection or post-separation treatment, which runs best below the separation unit's best flow rate.
According to still another exemplary embodiment, a method of pumping fluid in a fluid separation device for separating the fluid is provided, wherein the method comprises supplying a fluid inlet with the fluid with an inlet pressure, conducting the fluid supplied to the fluid inlet by a fluid conducting mechanism towards a connected fluidic path, and controlling the fluid conducting mechanism so that, regardless of a value of the inlet pressure, the fluid is continuously conducted away from the fluid inlet with a defined flow rate.
According to still another exemplary embodiment, a method of splitting a fluid flowing in a fluid separation device for separating a fluid is provided, wherein the method comprises supplying fluid to a fluid inlet conduit, splitting at least a part of the fluid supplied by the fluid inlet conduit between a first fluid outlet conduit and a second fluid outlet conduit both being in fluid communication with the fluid inlet conduit, and controlling the fluid flow so that the part of the fluid conducted to the first fluid outlet conduit is continuously conducted away from the fluid inlet conduit with a defined flow rate.
According to yet another exemplary embodiment, a method of pumping fluid at a variable flow rate in a fluid separation device for separating the fluid is provided, wherein the method comprises supplying a fluid inlet with the fluid at an inlet pressure, conducting the fluid supplied to the fluid inlet by a fluid conducting mechanism towards a connected fluidic path, and controlling the fluid conducting mechanism so that, regardless of a value of the inlet pressure, the fluid is continuously conducted away from the fluid inlet with an adequate flow rate to leave a constant flow rate for a mass spectroscopy device independent of a column flow rate.
According to yet another exemplary embodiment, a method for pumping a fluid in a fluid separation device for separating the fluid is provided, wherein the method comprises supplying the fluid to a fluid inlet conduit at an inlet flow rate; splitting the fluid supplied to the fluid inlet conduit such that a first part of the fluid flows from the fluid inlet conduit into a first outlet conduit and into a pump inlet of a pump at a first flow rate, and a second part of the fluid flows from the fluid inlet conduit into a second outlet conduit at a second flow rate; and controlling the second flow rate of the second part of the fluid, by controlling the pump such that, regardless of a value of an inlet pressure in the fluid inlet conduit, the first part of the fluid is continuously conducted away from the fluid inlet conduit at a defined value of the first flow rate, wherein the second flow rate is defined based on the defined value of the first flow rate.
In the context of this application, the term “inlet pressure” may particularly denote an actual pressure value which the fluid pump or the flow splitter is exposed to (or faces) at its fluidic inlet. Hence, this inlet pressure is the starting point on basis of which the fluid pump or the flow splitter adjusts its own operation. Whatever the value of the inlet pressure is, the fluid pump or the flow splitter will adjust its own operation (for instance an internal piston motion and/or a switching state of a fluidic valve) so that independently from this actual pressure value, an appropriate fluid flow is set at the fluid inlet to be intaken.
In the context of this application, the term “continuously conducted away” may particularly denote that the fluid pump (or the flow splitter) is operable so as to ensure that the flow through the inlet of the fluid pump (or through the first fluid outlet conduit) is controlled, for instance to be constant or to follow a predefined profile over a certain time interval, without uncontrollable sub intervals. For instance, the time interval over which the flow through the inlet is uninterruptedly controllable may be larger than one duty cycle, particularly larger than two duty cycles, of the fluid pump. For instance, the time interval over which the flow through the inlet is uninterruptedly controllable may be particularly larger than at least twice or at least three times of a time required by a reciprocating piston for moving in a chamber of the fluid pump before changing its motion direction. In contrast to conventional approaches, an exemplary embodiment may allow an uninterrupted definition of the subtracted flow without artifacts arising from an inversion of a motion direction of a reciprocating piston at reversal points.
In the context of this application, the terms “definable” and “defined” may particularly denote that it is possible to indicate a target flow to be subtracted from a fluid inlet interface of the fluid pump. The pump will then control its internal operation so as to permanently attain the target flow (which may be constant or time-dependent, depending on the definition). In an embodiment, the target flow may be “defined” as being an actually supplied flow (may be measured) minus a given value. This way the flow at the said second outlet will be exactly the given value, independent of the level of supplied flow.
In the context of this application, the term “flow rate” may particularly denote a fluid volume (or a fluid mass, especially when the fluid is exposed to substantial pressure levels at which compressibility becomes noticeable) flowing per time through the fluid inlet or through the first fluid outlet conduit.
In the context of this application, the term “flow splitter” may particularly denote a fluidic member which is configured for splitting or dividing an inlet flow from a fluid inlet conduit into exactly two or more than two outlet flows. A flow splitter may provide for a splitting of a source fluid flow into multiple target flows, simply a bifurcation of the flow stream. Examples for a flow splitter are a fluidic T-piece or a fluidic Y-piece (both having one inlet conduit and two outlet conduits) or a fluidic X-piece (having one inlet conduit and three outlet conduits, or having two inlet conduits and two outlet conduits).
In the context of this application, the arrangement of a first fluidic member “downstream” of a second fluidic member in a fluidic path may particularly denote that, in a fluid flow direction, the fluid passes firstly the second fluidic member and subsequently the first fluidic member. Correspondingly, the arrangement of a first fluidic member “upstream” of a second fluidic member in a fluidic path may particularly denote that in a fluid flow direction, the fluid passes firstly the first fluidic member and later the second fluidic member.
According to an exemplary embodiment, a fluid pump is provided which has the characteristic property that independently of a present inlet pressure, the fluid pump ensures that, at its fluid inlet, always a defined flow rate is subtracted or intaken. In other words, a precisely definable negative flow to be conducted away from the fluid inlet is the parameter which is controlled by the fluid pump. Hence, it can be ensured that even in the case of changes of the inlet pressure, the fluid conducting mechanism of the fluid pump will either increase the power of sucking fluid in its interior or will actively provide a counterforce if the inlet pressure becomes so large that without such an active counterforce the defined flow rate would be exceeded. Hence, the controlled parameter is the flow rate intaken by the fluid pump.
Particularly, this principle or even such a fluid pump may be advantageously implemented in a flow splitter to allow to subtract a defined flow rate from an inlet flow so that one or more other outlet fluid conduits will always carry a flow rate which is, in comparison to the inlet flow, reduced by the subtracted flow intaken by the fluid pump. Thus, an exceeding flow in the other outlet conduit(s) may be prevented by the fluid pump. At the same time, the other fluid outlet conduit(s) will not be influenced at all by this defined flow reduction because the fluid pump is not arranged in this or these other fluid outlet conduit(s) due to the bifurcated structure of the flow splitter.
Such embodiments may be advantageously implemented in a fluid separation device such as a HPLC because here it can be desired that the fluid flowing through a separation column should be significantly higher than a flow flowing towards a mass spectroscopy device downstream of the column. By arranging the separation column in the fluid inlet conduit, the fluid pump in the first fluid outlet conduit and the mass spectroscopy device in the second fluid outlet conduit, it can be controlled which fluid flow is subtracted by the fluid pump and will therefore not be conducted to the mass spectroscopy device. Consequently, the flow through the separation column may be adjusted to be larger than the flow through the mass spectroscopy device.
For example, flow rates as small as 0.5 ml/min or less can be conducted towards the mass spectroscopy device, whereas the flow rate at the separation column may for instance be 2 ml/min or more. Depending on required conditions for a certain fluid separation application, an active splitting which is to be performed by the fluid pump may be fine-tuned.
The previously described advantageous effects of flow reduction by a defined intake in a bifurcated fluidic path may be achieved continuously, i.e. basically without interruptions. Therefore, any discontinuity or unsteadiness of the fluid characteristic which for instance may conventionally occur at reversal points of reciprocating pistons of a fluid pump can be prevented by a corresponding operation of the fluid pump according to exemplary embodiments.
Next, further exemplary embodiments of the fluid pump will be explained. However, these embodiments also apply to the flow splitter, the fluid separation device, and the methods.
In an embodiment, the fluid pump comprises a control unit configured for controlling the fluid conducting mechanism so that, regardless of the value of the inlet pressure, the fluid is continuously conducted away from the fluid inlet with the definable, particularly with a constant, flow rate. Such a control unit may be a central processing unit (CPU) or a microprocessor. It may allow for a self-acting adjustment of the operation of the fluid pump to meet the given target flow rate, for instance based on sensor data, library data about solvent characteristics, calibration data about technical characteristic of the fluid pump or a user input.
In an embodiment, the fluid conducting mechanism is manually controllable by a human user so that, regardless of a value of the inlet pressure, the fluid is continuously conducted away from the fluid inlet with the definable, particularly with a constant, flow rate. In this embodiment, a user himself may control or define the flow rate at the pump inlet which extends the possible applications of the fluid pump to many technical fields.
In both embodiments, i.e. the adjustment by the control unit or by the user, it is possible to support the controlling entity with sensor measurements which may measure parameters such as pressure, flow rate, temperature, etc. at one or various positions of the fluidic system.
In an embodiment, the fluid conducting mechanism is controllable so that, regardless of the value of the inlet pressure, the fluid is continuously conducted away from the fluid inlet with a constant flow rate. A constant flow rate, i.e. a flowing fluid volume per time interval which does not change over time, may be advantageous to achieve a constant separation performance of a liquid chromatography apparatus.
In an embodiment, the fluid conducting mechanism is controllable so that when the inlet pressure has a value which would (in the absence of the controlling) result in a flow rate exceeding the definable flow rate, the fluid conducting mechanism applies a counterforce against the inlet pressure so as to adjust the flow rate to the definable flow rate. Thus, the fluid pump may actively fight against a force applied by the fluid. For instance, a piston of the fluid pump may apply a certain pressure contrary to a flowing direction of the fluid.
In an embodiment, the fluid conducting mechanism is controllable so that when the inlet pressure has a value which would (in the absence of the controlling) result in a flow rate below the definable flow rate, the fluid conducting mechanism enforces the inlet pressure by applying an additional sucking force so as to adjust the flow rate to the definable flow rate. Hence, under operation conditions being inverse to the previously mentioned scenario, i.e. a quite small flow rate of the fluid, the fluid pump may actively decrease the inlet pressure by applying a corresponding enforcing or enhancing additional sucking force so that the predefined fluid flow is intaken by the fluid pump.
In an embodiment, the fluid conducting mechanism comprises a piston being controllable for reciprocating within a chamber so as to conduct the fluid away from the fluid inlet with the definable flow rate when moving rearwardly in the chamber during a part of a duty cycle. In this context, the term “rearwardly” may particularly denote a motion of the piston within the chamber which is parallel to a motion direction of the streaming fluid. Therefore, when a piston moves rearwardly, fluid is sucked in via the fluid inlet. In contrast to this, a forwardly moving piston may move antiparallel to the streaming fluid so that a coupling of such a forwardly moving piston and the streaming would not result in fluid being sucked in the fluid inlet. Therefore, a piston may be decoupled from the fluid at the fluid inlet during the forward motion and may be coupled to the fluid at the fluid inlet during the backward motion. Since a piston in the chamber usually reciprocates, time intervals of coupling and decoupling the piston with the fluidic inlet may alternate. Particularly, a piston being coupled to the fluid inlet close to a reversal point (i.e. an end position of the piston in the chamber at which it changes from a rearward motion to a forward motion, or vice versa) might cause artifacts in a flow characteristic. Hence, it may also be possible to couple a piston to the fluid inlet only when moving along a central part of the chamber in the rearward direction, so that the piston may also be fluidically decoupled from the fluid inlet when travelling in the rearward direction but being sufficiently close to the end of the chamber.
In an embodiment, the fluid conducting mechanism comprises a further piston being controllable for reciprocating within a further chamber so as to, in cooperation with the previously mentioned piston, conduct the fluid away from the fluid inlet with the definable flow rate when moving rearwardly in the further chamber during a part of the duty cycle. According to such an embodiment, at least two pistons are used which together can ensure the continuous intake of a fluid with a definable flow rate. When the two pistons are operated with a phase difference with regard to their reciprocation, it can be ensured that there is always at least one piston moving in a rearward direction so that a continuous—particularly constant or at least definable (may be ramping or according to a specific shape)—subtracted flow rate is possible.
In an embodiment, any of the piston and the further piston is controllable for moving forwardly within the respective chamber during a part of the duty cycle so that, during moving forwardly, a respective piston is fluidically disconnected from the fluid inlet. Thus, it can be prevented that the subtracted fluid is reduced by a forwardly moving piston. However, in case of three or more pistons, it may also be possible to adjust (for instance reduce) a flow rate by intentionally coupling also one or more presently forwardly moving pistons to the fluid inlet.
In an embodiment, the fluid pump comprises a switchable fluidic valve having fluidic interfaces in fluid communication with the fluid inlet, with the fluidic path, with the chamber and with the further chamber. In an embodiment, such a switchable valve may be rotary valve. Such a rotary valve may be formed of two members or components being rotatable relative to one another. By taking this measure, it can be possible that fluid ports formed at certain positions of one of the members of the fluidic valve can be selectively brought in alignment or out of alignment with grooves formed in the other one of the members of the fluidic valve. Therefore, it is possible to properly define time intervals during which a respective one of the chambers and pistons is coupled to the fluid inlet and other time intervals where it is decoupled from the fluid inlet. The switching logic of the rotary valve may be configured so that at each time a defined target flow rate is subtracted by the presently fluid coupled pistons from the fluid inlet.
In an embodiment, the fluidic valve is switchable so as to fluidically disconnect a respective piston from the fluid inlet upon reversing its motion direction from a rearward motion to a forward motion (or a predefined time interval or spatial section before the reversing). According to this embodiment, the piston may be decoupled from the fluid inlet at (or close to) the reversal point of the reciprocating piston, i.e. at top or bottom dead point, so as to prevent artifacts which may specifically occur at such a reversal.
In an embodiment, the fluidic valve is switchable so as to fluidically connect a respective piston to the fluid inlet upon reversing its motion direction from a forward motion to a rearward motion (or a predefined time interval or spatial section after the reversing). Therefore, for instance a predefined delay time after reversing the motion direction from forward to rearward motion, the respective piston may be coupled to the fluid inlet so that it can again contribute to the subtraction of the fluid flow over the remaining part of the stroke width.
In an embodiment, the flow rate can be defined to be in a range between about 0.001 ml/min and about 10 ml/min. This is a proper range of flow rates for liquid chromatography applications. However, other flow rates are possible, especially when the size of pistons is altered (a smaller piston may correspond to a lower flow, a larger piston may correspond to a higher flow.
In an embodiment, the fluid pump comprises a waste container in fluid communication with the fluidic path. Such a waste container may be a pressureless container at the end of a fluidic conduit in which fluid (which is for instance no more needed) can be accumulated.
In an embodiment, the fluid conducting mechanism comprises a plurality of pistons (two, three, or more) each being controllable individually for reciprocating forwardly and rearwardly within a respective chamber to thereby conduct fluid away from the fluid inlet with the definable flow rate. The plurality of pistons may be controlled so that a difference between a sum of displaced fluid volume per time by all presently rearwardly moving pistons (and being presently in fluid communication with the fluid inlet, for instance as a consequence of a present switching state of the fluidic valve) and a sum of displaced fluid volume per time by all presently forwardly moving pistons (and being presently in fluid communication with the fluid inlet, for instance as a consequence of a present switching state of the fluidic valve) is constant over time. Thus, the integral forwardly displaced fluidic volume minus the integral backwardly fluid volume can be adjusted to the requirements. Other pistons being presently not in fluid communication with the fluid inlet, for instance as a consequence of a present switching state of the fluidic valve, do not contribute to the adjustment of the actual flow rate.
Next, further exemplary embodiments of the flow splitter will be explained. However, these embodiments also apply to the fluid pump, the fluid separation device, and the methods.
In an embodiment, a fluid pump (for instance a fluid pump having the above mentioned features) is arranged in the first fluid outlet conduit. Thus, fluid at exactly the defined flow rate may be sucked into the first fluid outlet conduit, so that the flow rate from the fluid inlet conduit minus the flow rate in the first fluid outlet conduit may be pumped into the second fluid outlet conduit. Thus, by a manipulation of fluid flow in the first fluid outlet conduit, a flow rate in the other second fluid outlet conduit may be set without the need to arrange any control member in the second fluid outlet conduit. Hence, the flow in the second fluid outlet conduit is not disturbed by any control member in the second fluid outlet conduit.
In an embodiment, the first fluid outlet conduit is fluidically coupled to the fluid inlet of the fluid pump. Thus, the fluid pump may selectively manipulate the flow condition in the first fluid outlet conduit.
In an embodiment, the flow splitter is configured as a fluidic T-piece or a fluidic Y-piece. Thus, the entire lines of the “T” or “Y” may have an inner lumen, and the crossing point of the lines may be fluidically coupled to one another.
In an embodiment, the flow splitter is configured so that the part of the fluid conducted to the second fluid outlet conduit is conducted away from the fluid inlet conduit with a flow rate in a range between about 0.001 ml/min and about 1 ml/min. However, other adjustable flow rates are possible, wherein the given range is advantageous for liquid chromatography applications in which a mass spectroscopy device with the need for small flow rates is arranged in the second fluid outlet conduit.
Next, further exemplary embodiments of the fluid separation device will be explained. However, these embodiments also apply to the fluid pump, the flow splitter, and the methods.
In an embodiment, the fluid pump and/or the flow splitter may be arranged downstream of the separation unit to operate a downstream device, such as detection or post-separation treatment, which runs best below the separation unit's best flow rate.
In an embodiment, the fluid pump and/or the flow splitter may be arranged upstream of the separation unit to operate the pump under its optimal conditions while the separation unit it operated best at a smaller flow rate.
In an embodiment, the fluid separation device comprises an electromagnetic radiation detector configured for detecting the separated fluid (i.e. different fractions thereof) and being arranged in the first fluid outlet conduit, i.e. in the same fluid conduit as the fluid pump. Such an electromagnetic radiation detector may be an ultraviolet detector having an ultraviolet radiation source and a corresponding detector. Both these components may be part of a flow cell. The separated fluid may be conducted between source and detector so that the detector can detect electromagnetic radiation after interaction with the fluid, for instance measuring absorbance, fluorescence, etc. More generally, the used detector may be based on an electromagnetic radiation detection principle of any appropriate wavelength, i.e. may detect electromagnetic radiation after interaction with the fluid, particularly may detect secondary electromagnetic radiation coming from the fluid in response to the irradiation of the fluid with primary electromagnetic radiation.
In an embodiment, the electromagnetic radiation detector is arranged upstream the fluid pump. Hence, the UV detector may be arranged in the same fluidic path as the fluid pump. By arranging it upstream of the fluid pump, the detection will not be negatively influenced by any effects caused by the fluid pump and any influence of the fluid pump on the fluid so as to obtain reproducible data.
In an embodiment, the fluid separation device comprises a mass spectroscopy device configured for analyzing the separated fluid and being arranged in the second fluid outlet conduit. Such a mass spectroscopy device can be arranged in the other fluid outlet conduit so that its fluid flow (which is usually quite small) can be defined by the fluid pump in the other parallel fluidic path. Hence, this flow rate control architecture will not negatively influence the operation of the mass spectroscopy device or the sample conducted thereto.
In an embodiment, a flow rate of the fluid in the mass spectroscopy device [[(80)]] is smaller than a flow rate of the fluid in the separation unit. For instance, it is possible to operate a separation column of a liquid chromatography device with a flow in a range between 1 ml/min and 5 ml/min, a flow in an outlet fluid conduit in which a mass spectroscopy device is arranged in a range between 0.01 ml/min and 1 ml/min. It is also possible to operate the fluid pump to subtract a flow rate (the defined flow rate) in a range between 1 ml/min and 5 ml/min.
The separation unit may be filled with a separating material. Such a separating material which may also be denoted as a stationary phase may be any material which allows an adjustable degree of interaction with a sample so as to be capable of separating different components of such a sample. The separating material may be a liquid chromatography column filling material or packing material comprising at least one of the group consisting of polystyrene, zeolite, polyvinylalcohol, polytetrafluorethylene, glass, polymeric powder, silicon dioxide, and silica gel, or any of above with chemically modified (coated, capped etc) surface. However, any packing material can be used which has material properties allowing an analyte passing through this material to be separated into different components, for instance due to different kinds of interactions or affinities between the packing material and fractions of the analyte.
At least a part of the separation unit may be filled with a fluid separating material, wherein the fluid separating material may comprise beads having a size in the range of essentially 0.1 μm to essentially 50 μm. Thus, these beads may be small particles which may be filled inside the separation section of the microfluidic device. The beads may have pores having a size in the range of essentially 0.01 μm to essentially 0.2 μm. The fluidic sample may be passed through the pores, wherein an interaction may occur between the fluidic sample and the pores.
The fluid separation device may be configured for separating components of the fluid. When a mobile phase including a fluidic sample passes through the fluid separation device, for instance by applying 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.
However, the fluid separation device may also be configured 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 of interest, the sample may be forced to pass the columns. 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 isolated as a purified sample.
The sample separation device may be configured to analyze at least one physical, chemical and/or biological parameter of at least one component of the mobile phase. The term “physical parameter” may particularly denote a size or a temperature of the fluid. The term “chemical parameter” may particularly denote a concentration of a fraction of the analyte, an affinity parameter, or the like. The term “biological parameter” may particularly denote a concentration of a protein, a gene or the like in a biochemical solution, a biological affinity of a component, etc.
The fluid separation device may be implemented in different technical environments, like a sensor device, a test device, a device for chemical, biological and/or pharmaceutical analysis, a capillary electrophoresis device, a capillary electrochromatography device, a liquid chromatography device, a gas chromatography device, an electronic measurement device, or a mass spectroscopy device. Particularly, the fluidic device may be a High Performance Liquid Chromatography device (HPLC) device by which different fractions of an analyte may be separated, examined and/or analyzed.
The separation unit may be a chromatographic column for separating components of the fluidic sample. Therefore, exemplary embodiments may be particularly implemented in the context of a liquid chromatography apparatus.
The fluid separation device may be configured to conduct a liquid mobile phase through the separation unit and optionally a further separation unit. As an alternative to a liquid mobile phase, a gaseous mobile phase or a mobile phase including solid particles may be processed using the fluid separation device. Also materials being mixtures of different phases (solid, liquid, gaseous) may be processed using exemplary embodiments.
The fluid separation device may be configured to conduct the fluid/mobile phase through the system with a high pressure, particularly of at least 600 bar, more particularly of at least 1200 bar.
The fluid separation device may be configured as a microfluidic device. The term “microfluidic device” may particularly denote a fluidic device as described herein which allows to convey fluid through microchannels having a dimension in the order of magnitude of less than 500 μm, particularly less than 200 μm, more particularly less than 100 μm or less than 50 μm or less. The fluid separation device may also be configured as a nanofluidic device. The term “nanofluidic device” may particularly denote a fluidic device as described herein which allows to convey fluid through nanochannels having even smaller dimensions than the microchannels.
Other devices, apparatus, systems, methods, features and advantages of the invention will be or will become apparent to one with skill in the art upon examination of the following figures and detailed description. It is intended that all such additional systems, methods, features and advantages be included within this description, be within the scope of the invention, and be protected by the accompanying claims.

BRIEF DESCRIPTION OF THE DRAWINGS

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 accompanying drawings. Features that are substantially or functionally equal or similar will be referred to by the same reference signs.

FIG. 1 illustrates a liquid chromatography system according to an exemplary embodiment.

FIG. 2 shows a more detailed view of a liquid chromatography system allowing for a quantitative splitting of flow into multiple streams.

FIG. 3 illustrates a flow splitter according to an exemplary embodiment of the invention having a fluid pump according to an exemplary embodiment of the invention.

FIG. 4 illustrates a fluid pump according to an exemplary embodiment of the invention.

FIG. 5A illustrates an operation mode of the fluid pump of FIG. 4, as described herein.

FIG. 5B illustrates another operation mode of the fluid pump of FIG. 4, as described herein.

FIG. 5C illustrates another operation mode of the fluid pump of FIG. 4, as described herein.

FIG. 5D illustrates another operation mode of the fluid pump of FIG. 4, as described herein.

FIG. 5E illustrates another operation mode of the fluid pump of FIG. 4, as described herein.

FIG. 5F illustrates another operation mode of the fluid pump of FIG. 4, as described herein.

FIG. 6 illustrates a fluid pump according to another exemplary embodiment of the invention.

FIG. 7 illustrates a fluid pump according to another exemplary embodiment of the invention.

The illustrations in the drawings are schematic.

DETAILED DESCRIPTION

Before describing in detail the drawings, some more general information with regard to exemplary embodiments of a flow subtracting pump will be given. In an embodiment, a reverse operation of a piston pump is used to control a split ratio.
In Liquid Chromatography (LC) systems there is often a requirement to have both an ultraviolet (or visual light) signal, and a mass spectroscopy signal captured at the same time. Modern UHPLC-systems exhibit high peak capacity, while at the same time they work with low sample amounts. Compromises are made in multiple aspects to achieve utmost performance.
However, both mentioned detection types (electromagnetic radiation-based, mass spectroscopy-based) are different with respect to flow sensitivity and often require their own critical operation set in order to deliver appropriate performance. While UHPLC is run at higher flow rates, modern mass spectroscopy systems find their optimum sensitivity in lower flow rates. For semi-preparative work a user may like to collect fractions, which is guided by the MS-signal. The above mentioned detectors may couple downstream of the separation column via a T-piece, which then allows parallel measurements.
According to an exemplary embodiment, the setup is like a normal two-detectors-parallel approach. A fluid pump according to an embodiment can be designed to basically deliver negative flow. For proper performance the fluid pump may be coupled to the outlet of the, for example, UV-detector, while the mass spectroscopy device is on the other arm of the T. In order now to have good flow rate on the mass spectroscopy arm while the liquid chromatography flow rate it too high, the fluid pump will subtract a controlled amount. Even in case the flow is non-constant the flow towards the mass spectroscopy path can be kept at a constant level by programming the flow subtraction. When recording the flow through the fluid pump, even the UV-trace can give exact quantitative information.
Referring now in greater detail to the drawings, FIG. 1 depicts a general schematic of a liquid separation system 10. A fluid drive or pump 20 receives a mobile phase from a solvent supply 25, typically via a degasser 27, which degases and thus reduces the amount of dissolved gases in the mobile phase. The pump 20—as a mobile phase drive—drives the mobile phase through a separating device 30 (such as a chromatographic column) comprising a stationary phase. A sampling unit 40 can be provided between the pump 20 and the separating device 30 in order to subject or add (often referred to as sample introduction) a sample fluid into the mobile phase. The stationary phase of the separating device 30 is configured for separating compounds of the sample liquid. A detector 50 is provided for detecting separated compounds of the sample fluid. A fractionating unit 60 (or a waste) can be provided for outputting separated compounds of sample fluid.
While the mobile phase can be comprised of one solvent only, it may also be mixed from plural solvents. Such mixing might be a low pressure mixing and provided upstream of the pump 20, so that the pump 20 already receives and pumps the mixed solvents as the mobile phase. Alternatively, the pump 20 might be comprised of plural individual pumping units, with plural of the pumping units each receiving and pumping a different solvent or mixture, so that the mixing of the mobile phase (as received by the separating device 30) occurs at high pressure and downstream of the pump 20 (or as part thereof). The composition (mixture) of the mobile phase may be kept constant over time, the so called isocratic mode, or varied over time, the so called gradient mode.
A data processing unit 70, which can be a conventional PC or workstation, might be coupled (as indicated by the dotted arrows) to one or more of the devices in the liquid separation system 10 in order to receive information and/or control operation. For example, the data processing unit 70 might control operation of the pump 20 (e.g. setting control parameters) and receive therefrom information regarding the actual working conditions (such as output pressure, flow rate, etc. at an outlet of the pump). The data processing unit 70 might also control operation of the solvent supply 25 (e.g. setting the solvent/s or solvent mixture to be supplied) and/or the degasser 27 (e.g. setting control parameters such as vacuum level) and might receive therefrom information regarding the actual working conditions (such as solvent composition supplied over time, flow rate, vacuum level, etc.). The data processing unit 70 might further control operation of the sampling unit 40 (e.g. controlling sample injection or synchronizing sample injection with operating conditions of the pump 20). The separating device 30 might also be controlled by the data processing unit 70 (e.g. selecting a specific flow path or column, setting operation temperature, etc.), and send—in return—information (e.g. operating conditions) to the data processing unit 70. Accordingly, the detector 50 might be controlled by the data processing unit 70 (e.g. with respect to spectral or wavelength settings, setting time constants, start/stop data acquisition), and send information (e.g. about the detected sample compounds) to the data processing unit 70. The data processing unit 70 might also control operation of the fractionating unit 60 (e.g. in conjunction with data received from the detector 50) and provide data back.
As can be taken from FIG. 1, the control unit 70 also controls a fluid pump 90. The fluid pump 90 is arranged downstream of the separation column 30. The fluid pump 90 has a fluid inlet 92 being supplied with separated fluid at a certain inlet pressure defined by the components upstream of a bifurcation point 85. An internal fluid conduction mechanism 94 (described in more detail referring to FIG. 4 and FIG. 5, for instance) of the fluid pump 90 is configured for conducting the fluid supplied to the fluid inlet 92 towards a connected fluidic path 96 (from where the fluid is introduced into the fractioner 60 or a waste container) with a defined flow rate of 2.5 ml/min. The fluid conducting mechanism 94 is configured so that, independently of a value of the inlet pressure provided by the pump 20, the fluid is continuously intaken in the fluid pump via the fluid inlet 92 with a definable flow rate. The flow rate through the separation column 30 is 3 ml/min. Therefore, by adjusting the flow rate through the fluid inlet 92 to a value of 2.5 ml/min, it is possible to ensure that the flow rate towards a fluidic path including a mass spectroscopy device 80 is, in this shown embodiment, 0.5 ml/min. This is highly advantageous because the relatively high flow rate through the separation column 30 allows for a high separation performance. On the other hand, the small flow rate of 0.5 ml/min meets the specific requirements of the mass spectroscopy device 80. Therefore, it is possible with the fluid pump 90 (being located in a flow path which differs from the flow path in which the separation column 30 and the mass spectroscopy device 80 are arranged) to indirectly adjust a flow rate value in the flow path including the mass spectroscopy device 80.
FIG. 2 shows another more detailed illustration of the liquid chromatography device 10 of FIG. 1.
As can be taken from FIG. 2 it is possible to mix different solvents, such as an aqueous solvent in a first vial 200 and an organic solvent in a second vial 202 to constitute a mobile phase to be pumped by pump 20. The two solvents in the vials 200, 202 may be mixed after being conducted through individual pump drives 204 and 206 respectively, which form a dual pump drive as pump 20. At a mixing T 208, the two solvents are mixed. An injection of a fluidic sample to the mobile phase formed by the two solvents occurs at the autosampler 40 (schematically shown in FIG. 2). A separation column 30 is located downstream the autosampler 40 and separates the sample injected into the mobile phase. After separation in the chromatography column 30, the fluid is split at bifurcation point 85 into a first path which connects to a mass spectroscopy detection device 80 and into another parallel second path coupled to an ultraviolet detector 50 for detecting the separated fractions of the fluidic sample. A recording computer may be part of the control unit 70.
An arrangement of the fluid pump 90 having fluid inlet 92 and internal fluid conducting mechanism 94 is provided downstream of the ultraviolet detector 50 for defining a defined flow at the fluid inlet 92. After having left the fluid pump 90, this part of the fluid can be accumulated in waste container 60. As can be taken from FIG. 2, the fluid pump 90 can be realized by two pistons reciprocating within corresponding chambers in combination with a certain fluidic switch. However, these components will be described in more detail below referring to FIG. 4.
FIG. 3 shows a flow splitter 300 according to an exemplary embodiment which can be implemented in the liquid chromatography apparatus 10 shown in FIG. 1 or FIG. 2. However, other applications are possible as well, because the flow splitter 300 is particularly advantageous for all applications in which a certain fluidic member 350 requires a certain reduced flow rate. Such a fluidic member 350 can be a mass spectroscopy device, a separation column, a detector, a pump, a sensor or any other fluidic component which requires or desires that a certain flow rate, particularly a reduced flow rate, flows through this fluidic member 350.
As can be taken from FIG. 3, the flow splitter 300 comprises a fluid inlet conduit 306. Through this fluid inlet conduit 306 a fluid (such as a gas or a liquid) is supplied. This fluid is supplied with an inlet flow rate FI. The fluid flowing through the fluid inlet conduit 306 is then divided or split at a splitting position 360 into a first fluid outlet conduit 302 and a second fluid outlet conduit 304. However, it is also possible to provide more than two fluid outlet conduits 302, 304 among which the fluid is split. The flow splitter 300 furthermore comprises a fluid pump 90 in the first fluid outlet conduit 302. A certain inlet pressure pI is applied to a fluid inlet 92 of the fluid pump 90 by the flowing fluid. The internal construction of the fluid pump 90 is such that independently of the inlet fluid pI, a certain flow rate FT is always subtracted or intaken at the fluid inlet 92. Therefore, the flow rate of fluid flowing through the fluidic member 350 is FI-FT. Hence, the fluid pump 90 reduces the flow rate of fluid flowing through the fluidic member 350 as compared to the inlet flow rate FI. By adjusting operation of the fluid pump 90, it is possible to adjust the flow through the fluidic member 350.
FIG. 3 furthermore shows that the control unit 70 controls operation of the pump 90, for instance for defining FT or for coordinating the reciprocation of various pistons in an interior thereof. Optionally, it is also possible that an input/output unit 370 is coupled to the control unit 70 so as to enable a user to provide control instructions or can be supplied with output information. Although not shown in FIG. 3, it is possible that one or more sensors is or are arranged in the fluidic path, i.e. in one or multiple of the conduits 306, 304, 302 or 96. After having left a fluid outlet 98 of the fluid pump 94, the fluid may be conducted into a waste container 308.
FIG. 4 shows a detailed view of the internal construction of a fluid conducting mechanism 94 of the fluid pump 90 according to an exemplary embodiment of the invention.
As can be shown in FIG. 4, the fluid conducting mechanism 94 comprises a first piston 400 which is controlled by control unit 70 for reciprocating within a first pump chamber 404 so as to conduct the fluid away from fluid inlet 92 with a definable flow rate when moving rearwardly in the first chamber 404 during a part of the duty cycle of the first piston 400. FIG. 4, as indicated by an arrow 420, shows the first piston 400 in an operation mode in which it moves rearwardly. “Rearwardly” means that the fluid entering via fluid inlet 92 and being conducted through a fluidic valve 408 is flowing basically in parallel to the motion direction of the first piston 400. In contrast to this, a forward operation of the first piston 400 would mean that the piston motion is antiparallel to the flow of the fluid which is indicated schematically by a further arrow 422 (the position of the arrow 422 in FIG. 4 should of course not be understood in a manner that medium flows into the piston 400).
Moreover, the fluid conducting mechanism 94 comprises a second piston 402 which is controlled by the control unit 70 as well for reciprocating within a separate second pump chamber 406. Therefore, in cooperation with the first piston 400, the fluid is conducted away continuously from the fluid inlet 92 with a definable constant flow rate FT. However, in the shown embodiment, the second piston 402 is presently not moving so that it presently does not contribute to intaking a certain fluid flow from the fluid inlet 92.
FIG. 4 furthermore schematically illustrates a switchable fluidic valve 408 comprising two valve members which are sandwiched perpendicular to the paper plane of FIG. 4. By rotation, the fluidic valve 408 is switchable so as to fluidically disconnect a respective piston 400, 402 from the fluid inlet 92 when this piston 400, 402 is moving forwardly or upon reversing its motion direction from a rearward motion to a forward motion. A fluid intaking performance of a corresponding piston 400 or 402 can only be obtained when the piston 400, 402 moves rearwardly.
A presently enabled fluidic path can be defined by the switching state of the fluidic valve 408 which can be changed by rotating the two valve members relative to one another as indicated schematically with a further arrow 424. One of the two members of the fluidic valve 408 has multiple ports 410 (a total of 7 in this case), whereas the other member of the fluidic valve 408 comprises grooves 426 (two in this case). FIG. 4 shows the valve 408 in an operation mode in which a fluidic path is enabled from the fluid inlet 92 through the lower arcuate groove 426 towards two ports 410 coupled to the two fluidic chambers 404 and 406, respectively. Furthermore, the fluid may be conducted past the rearwardly moving piston 400 towards a respective connected intermediate conduit 432. Correspondingly, an intermediate conduit 434 is provided for the second chamber 406 as well. Depending on the switching state of the fluidic valve 408 the intermediate conduits 432 or 434 may be connected to a drain conduit 436 from where the corresponding fluid may be conducted into waste container 308.
In order to obtain a continuous constant flow being subtracted from the fluid inlet 92, the reciprocation of the pistons 400, 402 may be coordinated by the control unit 70 as well as a switching state of the fluidic valve 408. This is performed in such a manner that the sum of the fluid flows subtracted by the presently rearwardly reciprocating pistons 400, 402 (which may be coupled to the fluid inlet 92) meets the desired defined flow rate value FT. Upon moving forwardly, the respective piston 400, 402 may be decoupled from the fluid inlet 92 because in this operation mode the respective piston 400, 402 would not contribute positively to the subtracting of fluid.
It is also possible that close to a reversal point 444 or 446 of the respective piston 400 or 402, artifacts or discontinuities of the intaken flow rate FT may arise by the respective pistons 400, 402 which could deteriorate the constant continuous subtraction of the defined fluid flow. Therefore, it is for instance possible that a certain piston 400 or 402 is only connected to the fluid inlet 92 while its fluid displacing surface 450 is within a central reciprocating region 448, and simultaneously providing that the respective other piston 400, 402 is moving rearwardly.
FIG. 5 again shows the system of FIG. 4 in a simplified illustration, whereas it can be taken from FIG. 5 that there is a constant continuous subtraction of the flow at the fluid inlet 92.
With regard to the embodiment of FIG. 5, the following describes in more detail the operation of the system.
The fluid pump 90 is equipped with the rotary valve 408 which is designed so the fluid pump 90 can intake liquid from the inlet line 92 into two piston pumps in parallel or in either one of them, while the other one is connected to waste. This allows continuous or seamless intake of fluid of a certain flow rate in either one of the pistons 400, 402. The piston movement is controlled by control unit 70 to provide a constant intake flow, so it is matched to the flow rate of the liquid fed into the fluid pump 90 via the inlet line 92. At any point in time the total movement of the receiving pistons 400, 402 equals the volumetric flow rate in the feeding line 92, providing a fast, direct and absolute means for maintaining (and if desired determining) volumetric flow.
Due to independent control of the two piston drives together with the rotary valve 408 design, the fluid pump 90 is capable of continuous pulsation-free fluid intake. This further improves the operability under dynamic conditions and the precision of the output data and flow rate control.
The fluid pump 90 may be operated in the following operation modes, as shown in FIG. 5:
State IDLE (FIG. 5A): In idle state the rotary valve 408 position is such that the intake line 92 is connected directly to the waste line 96 so the intake stays pressureless.
State INTAKE A (FIG. 5B): When operation is enabled, the valve 408 is rotated to detach the intake line 92 from the waste line 96 and connect it to both pistons 400, 402 simultaneously. The left piston 400 is then slowly retracted to keep the intake flow rate.
State INTAKE A END/B BEGIN (FIG. 5C): As the left piston 400 approaches its rearmost position, it is decelerated until it comes to halt, while the right piston 402 is accelerated synchronously.
State EJECT A/INTAKE B (FIG. 5D): The valve 408 is now rotated to keep the right piston 402 connected to intake 92, while the left piston 400 is detached from intake 92 and connected to the waste line 96. The content of the left piston 400 is now ejected into waste 96. When finished, the valve 408 is rotated back to its previous position connecting both pistons 400, 402 to intake.
State INTAKE B END/A BEGIN (FIG. 5E): As the right piston 402 approaches its rearmost position, it is decelerated until it comes to halt, while the left piston 400 is accelerated synchronously.
State INTAKE A/EJECT B (FIG. 5F): The valve 408 is rotated to keep the left piston 400 connected to intake 92, detach the right piston 402 and connect it to waste 96. After ejecting the right piston 402 into waste, the valve 408 is rotated to its previous position connecting both pistons 400, 402 to intake.
The scheme of FIG. 5A to FIG. 5F shows that, in an active state of the fluid pump 90, either one of the pistons 400, 402 sucks fluid from the inlet line 92 (first piston 400 in FIG. 5F, second piston 402 in FIG. 5D) or both pistons 400, 402 suck fluid from the inlet line 92 (FIG. 5C, FIG. 5E). The former scenario applies when one of the pistons 400, 402 presently moves forwardly and therefore is currently disconnected from the fluid inlet 92 (first piston 400 in FIG. 5D, second piston 402 in FIG. 5F), the latter scenario applies when both pistons 400, 402 presently move rearwardly. When one of the pistons 400, 402 presently moves forwardly, its content is drained towards the drain line 96. So it can be ensured that the fluid flow subtracted via fluid inlet 92 is continuously and uninterruptedly the same (or more generally: is continuously maintained at a desired value).
The fluid pump 90 may be equipped with high precision SSiC pistons and ball screw drives, driven by brushless DC motors which are field vector controlled by a 20 kHz control loop run on a specific processor in a FPGA on a main board.
FIG. 6 illustrates a fluid pump 600 according to another exemplary embodiment of the invention.
FIG. 6 comprises three pistons 400 in corresponding chambers 404 and also involves three different valves 602, 604, 606 each being switchable independently under the control of the control unit 70. In the respective drain lines 96, additional valves may be provided (not shown) so as to allow to close the drain lines 96. In the present operation mode shown in FIG. 6, valve 602 is open since the corresponding piston 400 is moving rearwardly. The second valve 604 is presently switched from an on-state to an off-state because the corresponding piston 400 is close to the reversal point, i.e. the upper dead point. The third valve 606 is presently off since the corresponding piston 400 moves forwardly.
FIG. 7 shows still another exemplary embodiment of a fluid pump 700 in which two switchable valves 408 are switched by a control unit 70, wherein each of the valves 408 operates two piston chamber pairs 400, 404. Again, as in FIG. 6, in the respective drain lines 96, additional valves may be provided (not shown) so as to allow to close the drain lines 96.
It should be noted that the term “comprising” does not exclude other elements or features and the term “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.
It will be understood that various aspects or details of the invention may be changed without departing from the scope of the invention. Furthermore, the foregoing description is for the purpose of illustration only, and not for the purpose of limitation—the invention being defined by the claims.

Claims

What is claimed is:

1. A method for pumping a fluid in a fluid separation device for separating the fluid, the method comprising:

supplying the fluid to a fluid inlet conduit at an inlet flow rate;

splitting the fluid supplied to the fluid inlet conduit such that a first part of the fluid flows from the fluid inlet conduit into a first outlet conduit and into a pump inlet of a pump at a first flow rate, and a second part of the fluid flows from the fluid inlet conduit into a second outlet conduit at a second flow rate; and

controlling the second flow rate of the second part of the fluid, by controlling the pump such that, regardless of a value of an inlet pressure in the fluid inlet conduit, the first part of the fluid is continuously conducted away from the fluid inlet conduit at a defined value of the first flow rate, wherein the second flow rate is defined based on the defined value of the first flow rate.

2. The method of claim 1, comprising at least one of:

controlling the pump such that the second flow rate is maintained at a constant value, or according to a predefined profile, over a desired time interval;

controlling the pump such that the second flow rate is maintained at a constant value, or according to a predefined profile, over a desired time interval that is larger than one duty cycle of the pump.

3. The method of claim 1, comprising at least one of:

controlling the pump such that the second flow rate is reduced relative to the inlet flow rate by the defined value;

controlling the pump such that the second flow rate is in a range between 0.01 ml/min and 1 ml/min.

4. The method of claim 1, wherein supplying the fluid to the fluid inlet conduit comprises outputting the fluid from a separation unit configured for separating the fluid.

5. The method of claim 4, comprising detecting the separated fluid in the first outlet conduit upstream of the pump inlet.

6. The method of claim 1, wherein controlling the pump comprises adjusting the pump based on the inlet pressure to maintain the first flow rate at the defined value.

7. The method of claim 1, wherein the pump comprises a first chamber communicating with the pump inlet, a second chamber communicating with the pump inlet, a first piston, and a second piston, and controlling the pump comprises controlling reciprocation of the first piston in the first chamber and reciprocation of the second piston in the second chamber.

8. The method of claim 7, wherein controlling the pump comprises at least one of:

selectively connecting and disconnecting the first chamber and the second chamber from the pump inlet;

selectively connecting and disconnecting the first chamber and the second chamber from a pump outlet of the pump.

9. The method of claim 7, wherein controlling the pump comprises switching a fluidic valve of the pump to perform at least one of:

10. The method of claim 7, wherein controlling the pump comprises controlling the reciprocation of the first piston and the second piston cooperatively to conduct the first part of the fluid away from the fluid inlet when the first piston is moving rearwardly in the first chamber and when the second piston is moving rearwardly in the second chamber.

11. The method of claim 10, wherein controlling the pump comprises controlling a fluidic valve switchable to selectively connect the first chamber to the first inlet and selectively connect the second chamber to the first inlet.

12. The method of claim 11, wherein controlling the pump comprises controlling the fluidic valve to connect the first chamber to the first inlet when the first piston reverses direction from moving forwardly to moving rearwardly, and to connect the second chamber to the first inlet when the second piston reverses direction from moving forwardly to moving rearwardly.

13. The method of claim 10, wherein controlling the pump comprises controlling the reciprocation of the first piston and the second piston such that the first piston is disconnected from the fluid inlet while the first piston is moving forwardly in the first chamber, and the second piston is disconnected from the fluid inlet while the second piston is moving forwardly in the second chamber.

14. The method of claim 13, wherein controlling the pump comprises controlling a fluidic valve switchable to selectively disconnect the first chamber to from the first inlet and selectively disconnect the second chamber from the first inlet.

15. The method of claim 14, wherein controlling the pump comprises controlling the fluidic valve to disconnect the first chamber from the first inlet when the first piston reverses direction from moving rearwardly to moving forwardly, and to disconnect the second chamber from the first inlet when the second piston reverses direction from moving rearwardly to moving forwardly.

16. The method of claim 1, wherein the pump comprises a plurality of pistons each being controllable for reciprocating forwardly and rearwardly within a respective chamber to thereby conduct fluid away from the fluid inlet with the definable flow rate (FT), wherein the plurality of pistons are controlled so that:

a sum of displaced fluid volume per time by all presently rearwardly moving pistons being in fluid communication with the fluid inlet,

minus

a sum of displaced fluid volume per time by all presently forwardly moving pistons being in fluid communication with the fluid inlet,

is constant over time.

17. The method of claim 1, comprising conducting the second part of the fluid at the second flow rate toward a fluidic member communicating with the second outlet conduit.

18. The method of claim 17, wherein the fluidic member has a desired flow rate, and controlling the pump comprises controlling the defined value of the first flow rate such that the second flow rate equals the desired flow rate.

19. The method of claim 17, comprising at least one of:

the fluidic member comprises a mass spectroscopy device and the separation unit comprises a chromatography device;

the fluidic member is selected from the group consisting of: a detector device; a device for chemical, biological and/or pharmaceutical analysis; a capillary electrophoresis device; a liquid chromatography device; an HPLC device; a gas chromatography device; a gel electrophoresis device; a mass spectroscopy device; a another pump; a sensor; and a combination of two or more of the foregoing.

20. The method of claim 17, comprising operating the fluidic member to analyze at least a portion of the second part of the fluid.