GB2481624A - Controller and piezoelectric actuator provides pressure ripple compensation in chromatographic pump drive - Google Patents

Abstract

A fluid pump for a fluid separation system for separating compounds of a fluidic sample in a mobile phase comprises a reciprocatable piston 1, a piston drive and a control unit 150 controlling the pump drive so that pressure ripples in a pressure profile of the fluid pump are at least partially compensated to bring the output pressure profile to target characteristic. The drive may be all piezoelectric or a mechanical base drive, e.g. a motor and gear driven ball screw or an eccentric driven crank, and a piezoelectric actuator 72 of low mass for making rapid compensating adjustments. Control is achieved by providing ripple-inverse pulses to the piezo actuator and may be based on an output sensor 58 detecting irregular ripples and/or a stored pump characteristic for compensating regular artifacts e.g. valve closures or base drive irregularities

Description

PIEZO-CONTROLLED AND/OR PRESSURE RIPPLE COMPENSATING

FLUID SEPARATION PUMP

BACKGROUND ART

[0001] The present invention relates to pumps, in particular in a high performance liquid chromatography application.

[0002] In high performance liquid chromatography (HPLC, see for instance http://en.wikipedia.org/wiki/HPLC), a liquid has to be provided usually at a very controlled flow rate (for instance in the range of microliters to milliliters per minute) and at high pressure (typically 20-100 MPa, 200-1000 bar, and beyond up to currently 200 MPa, 2000 bar) at which compressibility of the liquid becomes noticeable. For liquid separation in an HPLC system, a mobile phase comprising a sample fluid with compounds to be separated is driven through a stationary phase (such as a chromatographic column), thus separating different compounds of the sample fluid.

[0003] EP 0 309 596 discloses a pumping apparatus for delivering liquid at a high pressure, in particular for use in liquid chromatography, which comprises two pistons which reciprocate in pump chambers, respectively. The output of the first pump chamber is connected via a valve to the input of the second pump chamber.

The pistons are driven by linear drives, for instance, ball-screw spindles. The stroke volume displaced by the piston is freely adjustable by corresponding control of the angle by which the shaft of the drive motor is rotated during a stroke cycle. The control circuitry is operative to reduce the stroke volume when the flow rate which can be selected by user at the user interface is reduced, thus leading to reduced pulsations in the outflow of the pumping apparatus. The pumping apparatus can also be used for generating solvent gradients when a mixing valve connected to different solvent containers is coupled to the input of the pumping apparatus.

[0004] WO 2008/098615 by the same applicant Agilent Technologies discloses a pumping apparatus for a high performance liquid chromatography system. The pumping apparatus comprises a piston for reciprocation in a pump working chamber to compress liquid in the pump working chamber to a high pressure at which compressibility of the liquid becomes noticeable.

[0005] Particularly in modern HPLC with pressures rising up to 100 MPa and beyond and with the tendency of decreasing flow rates, a precise pumping performance is required.

DISCLOSURE

[0006] It is an object of the invention to provide a precisely operating pump, in particular for high pressure HPLC applications. The object is solved by the independent claims. Further embodiments are shown by the dependent claims.

[0007] According to an embodiment of the present invention, a fluid pump for use in a fluid separation system for separating compounds of a fluidic sample in a mobile phase is provided, the fluid pump comprising a reciprocatable piston configured for moving the mobile phase, a pump drive configured for driving the reciprocatable piston, and a control unit configured for controlling the pump drive so that pressure ripples in a pressure profile of the fluid pump are at least partially compensated to thereby bring the pressure profile in accordance with a predefined target characteristic.

[0008] According to another embodiment of the present invention, a method of operating a fluid pump for use in a fluid separation system for separating compounds of a fluidic sample in a mobile phase is provided, wherein the method comprises driving the reciprocatable piston to reciprocate for moving the mobile phase, and controlling the driving so that pressure ripples in a pressure profile of the fluid pump are at least partially compensated to thereby bring the pressure profile in accordance with a predefined target characteristic.

[0009] According to yet another embodiment of the present invention, a fluid pump for use in a fluid separation system for separating compounds of a fluidic sample in a mobile phase is provided, the fluid pump comprising a reciprocatable piston configured for moving the mobile phase, and a pump drive configured for driving the reciprocatable piston using a piezomechanism.

[0010] According to still another embodiment of the present invention, a method of operating a fluid pump for use in a fluid separation system for separating compounds of a fluidic sample in a mobile phase is provided, wherein the method comprises driving a reciprocatable piston (of the fluid pump) using a piezomechanism for moving the mobile phase.

[0011] According to still another embodiment of the present invention, a fluid separation system for separating compounds of a fluidic sample in a mobile phase is provided, the fluid separation system comprising a fluid pump having the above mentioned features and being configured to drive the mobile phase through the fluid separation system, and a separation unit, for instance a chromatographic column, adapted for separating compounds of the fluidic sample in the mobile phase.

[0012] The term "fluid pump" may particularly denote a mechanical device that moves fluid (such as liquid and/or gas) by pressure or suction.

[0013] The term "mobile phase" may particularly denote a fluidic material which can be conveyed through a fluidic path of a fluid pump under pressure and which may comprise, for instance, solvent. Such a solvent may be mixed with an actual fluidic sample, i.e. a sample having components which should be analyzed, and can be conducted through the fluid separation system. The mobile phase may comprise one or more fluidic components with partial volume contributions being constant or varying over time.

[0014] The term "fluid separation system" may particularly denote any apparatus which is capable of separating a fluidic sample into various components or fractions.

Particularly, such a fluid separation system may be a chromatographic separation system, more particularly a liquid chromatography apparatus, even more particularly a high performance liquid chromatography apparatus.

[0015] The term "reciprocatable piston" may particularly denote a piston which can be moved within a cylindrical chamber in one direction up to a first reversal point. Subsequently, the piston may change direction of motion and may move towards a second reversal point opposing the first reversal point. The piston then continues this motion between the two opposing reversal points to move up and down in an alternating manner. Due to this motion, a mobile phase within the cylinder or housing is displaced and is therefore pumped towards a destination.

[0016] The term "pump drive" may particularly denote a mechanical device which actually forces motion of the piston. Such a pump drive may therefore be a motor, particularly a linear motor having a drive performance resulting in a reciprocation of the piston.

[0017] The term "control unit" may particularly denote a processor or the like which is capable of providing the pump drive with control signals according to which the piston will be moved. The control signals may be determined or selected by the control unit based on one or more inputs such as a predefined drive scheme and/or a sensor signal indicative of at least one parameter within the pumping system.

[0018] The term "pressure ripples" may particularly denote artifacts in a pressure-over-time diagram in terms of deviations from a predefined pressure characteristics. Hence, pressure ripples may be pressure fluctuations, pressure pulsations or any other pressure variations which deviate from a desired target behavior. Without wishing to be bound to a specific theory it is presently believed that such pressure ripples may occur when the reciprocating piston is close to its reversal points and/or at points of time at which an inlet valve upstream the piston and/or an outlet valve downstream the piston is or are switched. In an embodiment, a desired pressure profile may be a constant pressure over time (at least over a certain time interval), so that in this embodiment pressure ripples may be dips or peaks or other signal artifacts which deviate from the desired behavior. It is also possible that pressure ripples occur due to the inharmonic behavior of the integral parts of the pump, like e.g. the nonlinear or uneven flank lead of a ball bearing spindle. Also rriechanical uneven or unsymmetrical parts can cause such pressure ripples.

[0019] The term "predetermined target characteristic" may particularly denote a pumping characteristic which is desired in the context of a fluid separation procedure in the fluid separation system. For instance, such a predefined target characteristic may be but is not limited to a pumping pressure which is constant over time.

[0020] The term "piezomechanism" may particularly denote a pump drive mechanism which is based on the piezo effect. As known by those skilled in the art, piezoelectricity is the ability of a structure of specific material to be mechanically elongated or contracted upon applying an electric signal to the structure. In other words, using an electric signal such as a voltage or a current, a spatial dimension of the piezoelectric structure may be changed. The structure experiencing a change of dimension may act, directly or indirectly, on the piston to promote a reciprocation of the piston.

[0021] According to a first aspect of the invention, a pump drive mechanism may be provided in which an undesired impact of pressure ripples on a pressure profile can be suppressed or even eliminated by correspondingly modifying a pump drive signal so that deviations between the actual pressure profile and a predefined target characteristic are reduced or even removed.

[0022] According to another second aspect of the invention, a pump drive mechanism is provided which makes use of the piezoelectric effect, thereby allowing a fast and precise adjustment of the reciprocation of the piston in terms of time and stroke path, thereby also allowing to compensate for very small pressure ripples or for pumping particularly in the nano regime.

[0023] In the following, further exemplary embodiments of the fluid pumps of the above aspects will be explained. However, these embodiments also apply to the fluid separation system and to the methods.

[0024] In an embodiment, the pump drive may be configured for driving the reciprocatable piston using a piezomechanism. In one embodiment, a piezomechanism alone may be used as the only drive for the pump, i.e. without further drive mechanisms. In another embodiment, a piezomechanism may be combined with another linear pump drive mechanism such as a ball-screw drive.

[0025] In an embodiment, the fluid pump may comprise a sensor which is configured for sensing (for instance continuously) an actual pressure profile of the fluid pump. In this embodiment, the control unit may be configured for controlling the pump drive so that the actual pressure profile is brought in accordance with (or is at least approached to) the predefined target characteristic. This can be performed nearly in real time, particularly when a fast operable piezomechanism is implemented. In other words, a sensor may be arranged in the fluidic path at an appropriate position so as to sense the actual pressure profile which may also include ripples. The presence of such ripples may then be suppressed by correspondingly adjusting the operation of the pump drive.

[0026] For example, the actual pressure profile may show a periodic repetition of pressure ripples or the like. In this case, the sensed pressure profile may also be interpolated to the future so as to adjust the operation of the pump drive before the occurrence of the next ripples.

[0027] In another embodiment, the sensor and particularly a very fast piezomechanism may be configured so that during detecting the appearance of an artifact in the actual pressure profile the pump drive is already adapted so as to at least partially compensate the present ripple. In this context, it is also possible to use pre-stored patterns of pressure ripples for predicting the shape of a presently occurring pressure ripple. It is also possible that some kind of servomechanism is used which is based on the measurement of a parameter indicative of the present pressure conditions.

[0028] For example, the one or more sensors may be a flow sensor or a pressure sensor. A flow sensor is capable of measuring the flow rate, i.e. pumped volume per time interval, whereas a pressure sensor is capable of measuring an actual pressure value in the fluidic path.

[0029] In an alternative embodiment (which may or may not have a sensor), the fluid pump may comprise a storage unit accessible by the control unit and storing data being indicative of at least one compensation scheme for controlling the pump drive so that a characteristic pressure profile (particularly a pressure profile which the pump would show in the absence of a compensation) of the fluid pump is brought in accordance with the predefined target characteristic. Such a storage device may be a memory storing experimental data, e.g. of a separate tooling stage, and/or expert knowledge with regard to the compensation of reciprocating piston pumps to suppress artifacts such as pressure ripples. Such a compensation scheme may be derived in advance experimentally or theoretically. For example, it is possible that a sensor of the above-mentioned type is arranged in the fluidic path temporarily or permanently so as to measure an actual pumping performance of the fluid pump without compensation. Then, a pattern of artifacts may be analyzed by pattern analysis or the like. A regulation of the pump drive can be adjusted so that the used compensation scheme addresses such a for instance periodic pattern of artifacts.

[0030] In an embodiment, it is possible to perform a calibration measurement once (particularly before actually using the pump in the context of sample separation) in order to determine the pressure profile of the pump. Corresponding measurement curves may then be deposited in a database which can be accessed by the control unit. Hence, no actual measurement with a sensor is needed in such an embodiment, since the control unit can then rely on the curves indicative of the actual behavior of the pump, and which may also include control curves which can be applied from the control unit to the pump drive.

[0031] In an embodiment, the suppressed pressure ripples may be ripples of a periodic pattern in the pressure profile of the fluid pump. The knowledge of a periodic pattern of signal artifacts may allow to predict already in advance at which time intervals a compensation would be helpful. Such a periodic pattern may relate to a constant time interval between leading edges of consecutive pressure ripples.

In other words, the periodicity may refer to a distance of pressure ripples in the time domain. Additionally or alternatively, such a periodic pattern may relate to a shape of a pressure ripple between a leading edge and a trailing edge which shape may be equal or basically equal for different pressure ripples. The a priori knowledge of at least one of these types of periodicity, particularly the knowledge of both these types, may allow to at least partially compensate them with high precision.

[0032] In an embodiment, the fluid pump may comprise a fluid inlet valve which may be arranged upstream with respect to a housing of the piston. Additionally or alternatively, the fluid pump may comprise a fluid outlet valve arranged downstream with respect to the housing of the piston. The fluid inlet valve and/or the fluid outlet valve may be switchable for being synchronized with a reciprocation of the piston.

Valve switching may provide a contribution to the pressure ripples. The fluid inlet valve may be arranged between one or more containers including one or more components of the mobile phase arranged upstream of the chamber in which the piston reciprocates. The fluid outlet valve may be located downstream of an outlet opening of the cylinder in which the piston reciprocates. Since the fluid inlet valve and/or the fluid outlet valve may be operated in accordance with a periodic pattern or scheme, it is also likely to expect that the pressure ripples occur in a periodic pattern. This may render a prediction of a compensation manageable.

[0033] The sensor may be arranged downstream the fluid outlet valve. In an embodiment, the sensor may be arranged directly downstream the fluid outlet valve, i.e. directly after the fluid outlet valve in a flowing direction of the mobile phase. This has turned out as a reasonable position for accurately detecting pressure ripples, since an expected origin of the pressure ripples, i.e. the fluid outlet valve, is then spatially close to the arrangement of the sensor in such an embodiment.

[0034] However, in an alternative embodiment, the sensor may be arranged directly upstream of a separation unit such as a chromatographic column, since the pressure characteristics at the position of the column determine the influence of pressure ripples on the actual fluid separation process.

[0035] According to an embodiment, the predefined target characteristic is free of the pressure ripples. For instance, the predefined target characteristic may be a constant pumping pressure over time.

[0036] Again referring to the above-described piezomechanism, one embodiment may be characterized in that the reciprocatable piston is exclusively driven by the piezomechanism. In other words, there is no further pump drive apart from the one or more piezomechanisms for driving the piston in such an embodiment. This embodiment can particularly be realized in the context of microfluidic and nanofluidic devices in which very small pump rates are desired. However, since the skilled person is also aware of piezo drives with high travel ranges, i.e. distances between two reversal points of a piston, other embodiments may also operate in accordance with higher pump rates. For instance, a piezomechanism allowing for a larger stroke width may be realized using a N-214, N-215 or N-216 NEXLINE® Linear Motor/Actuator. Such a piezomechanism is for instance available via http://www.physikinstrumente.com/en/products/index.php.

[0037] In one embodiment, the pump drive may comprise a single piezo drive as the one described above. However, alternatively, the pump drive may comprise a plurality of piezo drives cooperating for driving the reciprocatable piston. For instance, such piezo drives may be serially coupled so that the individual stroke heights of the individual piezo drives are summed. In such an embodiment, the piezo drives may be arranged along a linear axis. This embodiment may have particularly the advantage that a large stroke width can be combined with a very fast operation and a high precision.

[0038] In an alternative embodiment, the pump drive may comprise a base drive unit and a piezo drive, wherein the base drive unit may be configured for providing a base drive component for driving the piston, and the piezo drive unit may be configured for providing an additional drive component for driving the piston. In an embodiment, the base drive unit may provide a piston drive contribution continuously or permanently, whereas the piezo drive unit may provide a piston drive contribution only on demand, i.e. only within activation intervals while being inactive during deactivation intervals. In such an embodiment, a main contribution to the reciprocation motion of the piston is provided by the base drive. For example, at least 80%, particularly at least 90%, more particularly at least 95% of the pumping amplitude may be delivered by the base drive unit. The additional portion of the pumping amplitude may then be provided by a piezo drive unit which then allows a fine adjustment or fine-tuning of the pumping characteristic. Therefore, any conventional linear drive may provide a sufficiently large amount of pumping power to obtain a high stroke width, whereas a high precision and a high speed of changing or adapting a reciprocation characteristic can be added by the piezo drive unit.

[0039] Hence, the base drive component may have a larger amplitude than the additional drive component. The term "amplitude" may relate to a partial stroke width. In other words, the base drive component may provide a larger partial stroke width of the piston as compared to the additional drive component providing a smaller partial stroke width of the piston. The larger partial stroke width and smaller partial stroke width in sum may result in a total stroke width of the piston within the housing.

[0040] In an embodiment, the control unit may be configured for activating the additional drive component only upon determining a discrepancy between an actual pressure profile of the fluid pump and a predefined target characteristic of the pressure profile. In other words, the additional drive component being realized as a piezo drive unit may remain inactive until a certain discrepancy is detected or expected or predicted. This may allow for a simple control of the system, since in a normal state, only one of the two or more drives needs to be activated.

[0041] In an embodiment, the base drive unit may be realized as a linear motor.

For example, such a linear motor may be an eccentric drive mechanism having an eccentrically mounted connection rod which is moved by a rotating shaft. A crankshaft mechanism transforms a rotating motion into a reciprocating motion.

Alternatively, it is possible to use a ball-screw spindle mechanism as a linear motor in which a rotating spindle transforms a rotation motion to a linear motion of a member moving in one direction or the opposite direction along the screw.

[0042] In an embodiment, the additional drive component may be configured to provide a fine adjustment for driving the reciprocatable piston. In this embodiment, a base component for the drive amplitude may be provided by the base drive component, and the additional drive component only adds a relatively small amount of for instance several percent of the amplitude to this main drive. Therefore, a fine adjustment of the piston trajectory may be performed. Alternatively, it is possible that the additional drive component is configured for providing a correction of driving the reciprocatable piston. In this embodiment the piezo drive may compensate for detected or expected or predicted signal artifacts so as to add the inverse of the artifact as a correction.

[0043] The additional drive component may be arranged spatially between the reciprocatable piston and the base drive unit. In other words, the additional drive component may be sandwiched between piston and base drive unit. By taking this measure, the additional drive component directly acts on the reciprocatable piston so as to be capable of transferring its motion contribution in a very precise manner.

[0044] In an embodiment, the fluid pump may be configured as a low flow pump e.g. a nanopump or a capillary pump (CAP or NANO System). Flow rates may be from 1 p1/mm up to 100 p1/mm for CAP and 0.01 p1/mm to 4 p1/mm for current nanopump (compare: http;L/wwwchernaj.com/en-US/Products/nstrurnents/Ic/1 2OOseriesnanoflowpump/ages/gp849taspx).

[0045] Correspondingly, the fluid separation device for handling a fluidic sample may be a nanofluidic device having chambers and/or channels of nanometers or micrometers that allow the passage of the fluidic sample. The chambers or channels, particularly when the flow rate is in the order of magnitude of nI/mm, may be generally 100 nanometer to 1000 micrometer in diameter, by way of examples. It is however also possible that the device for handling a fluidic sample is a microfluidic device, particularly when the flow rate is in the order of magnitude of nI/mm or p1/mm, having chambers or channels generally in an order of magnitude between 1 pm and 1000 pm in diameter. Particularly in such microfluidic or nanofluidic devices, conventional drive mechanisms may be insufficient to provide as required accuracy. However, using a piezoelectric drive does not only allow for a fast adjustment of the pumping profile but also to perform very small adjustments.

Due to the small flow rates achievable with a piezo drive, the fluid separation device may also be adapted for splittless applications.

[0046] In an embodiment, a stroke width of the piston may be less than about 7 mm. Particularly, a stroke width may be less than about 3 mm. The term "stroke width of the piston" may denote a spatial distance between a first (for instance lower) reversal point and a second (for instance upper) reversal point of the piston reciprocating in a housing, Particularly for pistons with small stroke widths, a piezo drive may be an appropriate solution. In an embodiment, the stroke width of the piston may be larger than 0.5 mm, particularly larger than 1 mm.

[0047] A flow rate of the fluid pump may be less than about 500 nI/mm, particularly less than about 200 nI/mm. Even with these small flow rates, a piezo drive may be sufficient to perform compensations with high accuracy.

[0048] In an embodiment, a force transmission body such as a force transmission ball may be arranged between the reciprocatable piston and the piezomechanism. Such a ball may abut at one end thereof to the piezomechanism, whereas another end of the ball abuts against the reciprocatable piston arrangement. Therefore, discrepancies between a motion direction of the piezomechanism and the motion direction of the piston arrangement may be compensated for, since the ball can be moved regardless of slightly inclined motion directions. However, in embodiments in which the motion direction of the piston is synchronized to the motion direction of the piezo drive, it is also possible to omit such a force transmission ball. In an embodiment, the force transmission ball may be made of ruby.

[0049] The piezomechanism may be arranged to directly act on the reciprocatable piston. In other words, it is possible that the piezomechanism directly contacts the reciprocatable piston to therefore further increase the accuracy.

[0050] In an embodiment, the pump may be configured as a chromatographic pump for a chromatographic separation procedure.

[0051] Embodiments of the invention may provide a pumping apparatus which comprises two pistons which reciprocate in pump chambers, respectively, wherein each of the piston-pump chamber arrangements may be configured as disclosed herein. The output of the first pump chamber may be connected via a valve to the input of the second pump chamber. Hence, the two (or more) pump chambers may be serially connected.

[0052] In the following, further exemplary embodiments of the fluid separation system will be explained. However, these embodiments also apply to the fluid pumps and to the methods.

[0053] The separation unit may be located downstream the fluid pump.

[0054] Embodiments of the present invention might be embodied based on most conventionally available HPLC systems, such as the Agilent 1200 Series Rapid Resolution LC system or the Agilent 1100 HPLC series (both provided by the applicant Agilent Technologies -see www.apilent.com -which shall be incorporated herein by reference.

[0055] The separating device preferably comprises a chromatographic column providing the stationary phase. The column might be a Ceramic or steel tube (for instance with a diameter from 50 pm to 5 mm and a length of 1 cm to 1 m) or a microfluidic column (as disclosed for instance in EP 1577012 or the Agilent 1200 Series HPLC-Chip/MS System provided by the applicant Agilent Technologies, see for instance http://www.chem.aqilent.com/Scripts/PDS.asr?lPaqe=38308). For example, a slurry can be prepared with a powder of the stationary phase and then -12-poured and pressed into the column. The individual components are retained by the stationary phase differently and separate from each other while they are propagating at different speeds through the column with the eluent. At the end of the column they elute one at a time. During the entire chromatography process the eluent might be also collected in a series of fractions. The stationary phase or adsorbent in column chromatography usually is a solid material. The most common stationary phase for column chromatography is silica gel, followed by alumina.

Cellulose powder has often been used in the past. Also possible are ion exchange chromatography, reversed-phase chromatography (RP), affinity chromatography or expanded bed adsorption (EBA). The stationary phases are usually finely ground powders or gels and/or are microporous for an increased surface, though in EBA a fluidized bed is used.

[0056] The mobile phase (or eluent) can be either a pure solvent or a mixture of different solvents. It can be chosen for instance to reduce or even minimize the retention of the compounds of interest and/or the amount of mobile phase to run the chromatography. The mobile phase can also been chosen so that the different compounds can be separated effectively. The mobile phase might comprise an organic solvent like for instance methanol or acetonitrile, often diluted with water.

For gradient operation water and organic is delivered in separate bottles, from which the gradient pump delivers a programmed blend to the system. Other commonly used solvents may be isopropanol, THF, hexane, ethanol and/or any combination thereof or any combination of these with aforementioned solvents.

[0057] The fluidic sample might comprise any type of process liquid, natural sample like juice, body fluids like plasma or it may be the result of a reaction like from a fermentation broth.

[0058] The pressure in the mobile phase might range from 2-200 MPa (20 to 2000 bar), in particular 10-1 50 MPa (100 to 1500 bar), and more particular 50-1 20 MPa (500 to 1200 bar).

[0059] The HPLC system might further comprise a sampling unit for introducing the sample fluid into the mobile phase stream, a detector for detecting separated compounds of the sample fluid, a fractionating unit for outputting separated compounds of the sample fluid, or any combination thereof.

[0060] In view of the controlled suppression of pressure ripples which may be achieved according to exemplary embodiments of the invention, it may be possible to omit damper elements which may otherwise be used to provide for some suppression of ripples. Hence, in an embodiment, the fluid pump or the sample separation system may be free of such damper units.

[0061] 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 or routines can be preferably applied in or by the control unit.

BRIEF DESCRIPTION OF DRAWINGS

[0062] 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 drawing(s). Features that are substantially or functionally equal or similar will be referred to by the same reference sign(s).

[0063] Figure 1 shows a liquid separation system, in accordance with embodiments of the present invention, for instance used in high performance liquid chromatography (HPLC).

[0064] Fig. 2 illustrates a fluid pump having a combination of a ball screw spindle mechanism and a piezomechanism.

[0065] Fig. 3 illustrates a fluid pump according to another exemplary embodiment having, as a drive, a combination of a piezoelectric drive and an eccentric drive mechanism using a crankshaft.

[0066] Fig. 4 shows a detailed view of a force transmission between a piezoelectric drive and a piston via a ruby ball.

[0067] Fig. 5 shows a fluid pump according to another exemplary embodiment of the invention using a cascade of serially coupled piezoelectric drives for pumping a -14-fluidic sample.

[0068] Fig. 6 shows an actual pressure profile of a fluid pump without compensation, and a control curve to be applied to a piezo drive for smoothing pressure ripples in the actual pressure profile.

[0069] Fig. 7 shows a similar diagram as Fig. 6 for compensation of periodic and aperiodic pressure ripples.

[0070] Fig. 8 and Fig. 9 show fluid pumps according to other exemplary embodiments of the invention.

[0071] Referring now in greater detail to the drawings, Fig. I depicts a general schematic of a liquid separation system 10. A 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 fluidic sample into the mobile phase. The stationary phase of the separating device 30 is adapted for separating compounds of the fluidic sample. A detector 50 is provided for detecting separated compounds of the fluidic sample. A fractionating unit 60 can be provided for outputting separated compounds of the fluidic sample.

[0072] 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 und 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.

[0073] 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 (for instance setting control parameters) and receive therefrom information regarding the actual working conditions (such as output pressure, flow rate, etc. at an outlet of the pump). The data processing unit 70 might also control operation of the solvent supply 25 (for instance setting the solvent/s or solvent mixture to be supplied) and/or the degasser 27 (for instance setting control parameters such as vacuum level) and 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 (for instance controlling sample injection or synchronization sample injection with operating conditions of the pump 20). The separating device 30 might also be controlled by the data processing unit 70 (for instance selecting a specific flow path or column, setting operation temperature, etc.), and send -in return -information (for instance operating conditions) to the data processing unit 70. Accordingly, the detector 50 might be controlled by the data processing unit 70 (for instance with respect to spectral or wavelength settings, setting time constants, start/stop data acquisition), and send information (for instance 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 (for instance in conjunction with data received from the detector 50) and provides data back.

[0074] Reference numeral 90 schematically illustrates a switchable valve which is controllable for selectively enabling or disabling specific fluidic paths within apparatus 10. The switchable valve 90 is not limited to the position between the pump 20 and the separating device 30 and can also be implemented at other positions, depending on the application.

[0075] The exemplary embodiments of fluid pumps which will be described referring to Fig. 2 to Fig. 7 are examples for the configuration of the fluid pump 20 shown in Fig. 1.

[0076] Pumping apparatuses for delivering liquid at a high pressure shall first be described in more general terms. The pressure applied by the piston provides a noticeable compression of the liquid. The piston of the pumping apparatus is reciprocated in the pump working chamber containing the respective liquid. The pump working chamber may be coupled to one or more valves in order to permit liquid flow unidirectional only. Driving the piston may be performed by a drive unit which permits pressurizing of the liquid in the pump working chamber to high pressure.

[0077] Fig. 2 depicts an embodiment of a fluid pump 160 according to an exemplary embodiment of the invention.

[0078] The fluid pump 160 comprises a piston 1 reciprocating in a pump working chamber 9 formed by a cylindrical inner bore of a pump cylinder body 3. Such a cylindrical architecture may be advantageous in rotationally symmetric architectures since it is simple in construction and particularly appropriate for larger flow rates.

Alternatively, pump cylinder body 3 can also have a rectangular or square geometry.

Hence, particularly in micro structured assemblies for nano flow applications, it can also be a chamber formed of other materials like ceramics and may have other forms e.g. squared or the like. The pump working chamber 9 has an inlet port 4' and an outlet port 5'. A capillary 5 having an inner bore 4 is coupled to the inlet port 4' and also couples an inlet valve 52 with the pump working chamber 9 to permit liquid flow only unidirectional into the pump working chamber 9. The reciprocating movements are driven under control of a control unit 150, which operates the piston 1 using a piezomechanism 72 and a spindle drive mechanism (described below in more detail) via an actuator 7 coupled for instance via a ball 8 (embedded in a recess 10) and a piston holder 6.

[0079] A seal 11 is provided for sealing off the pump working chamber 9 at an opening in the pump cylinder body 3 where the piston 1 moves into the pump working chamber 9. Thus, unwanted liquid flow-out can be prevented. Guiding of the piston 1 into the pumping chamber 9 can be supported by a guiding element 12.

[0080] The liquid in the pump working chamber 9 is compressed to a high pressure before being delivered via the outlet port 5' and the capillary 5 into a liquid receiving device (not shown in Fig. 2).

[0081] Typical solvents, as used in the pumping apparatus as shown in Fig. 2, can be water, Acetonitrile, Tetrahydrofurane, Methanol, Hexane or any other solvents used in HPLC.

[0082] The fluid pump 160 shown in Fig. 2 is used in a chromatographic sample separation system for separating components of a fluidic sample in mobile phase.

The mobile phase is formed by a mixture of one or more fluidic components which are mixed upstream of the fluid inlet valve 52 receiving the mobile phase, as indicated by arrow 54. When the inlet valve 52 is open, the fluid may flow in the pumping chamber 9. After being pumped through the pumping chamber 9 by the reciprocation of the piston 1, the fluid exists through a fluid outlet valve 56. Directly downstream of the fluid outlet valve 56, a flow sensor 58 is provided. The flow sensor 58 is capable of measuring the flow rate (every flow sensor can also have a pressure sensor) at the shown position or at any other position which is suitable for the application. Downstream the fluid sensor 58, see arrow 62, a fluidic sample may be mixed to the mobile phase and may be separated in a chromatographic separation column (also not shown in Fig. 2). Furthermore, a ball screw arrangement 64 is shown which is coupled to a tooth gear 66. The tooth gear 66 is coupled to a further gear 68 which is rotated by a motor 170, for instance a servomotor. Motor 170 is controlled by the control unit 150.

[0083] In addition to the described ball screw arrangement 64 for actuating the piston 1, the piezomotor 72 is provided and arranged between e.g. the actuator 7 of the spindle driven ball screw mechanism driven by motor 170 (denoted as base drive unit in the following) on the one hand and ruby ball 8 on the other hand. The piezomechanism 72 is also driven under control of the control unit 150. In other words, the base drive unit 170 provides a large amplitude for moving the piston 1 in a reciprocating way. As an add on for precisely controlling or fine tuning the movement of the piston 1 to suppress pressure ripples in the fluidic path 5, the piezomechanism 72 acts as an additional drive component for fast driving the piston 1, since the mechanical mass of the piezo is much smaller and can be moved faster than the gear combination and without clearance.

[0084] As can be taken from Fig. 2, an input/output unit 74 is bidirectionally coupled to the control unit 150. Via the input/output unit 74, a user (or a firmware of a total system respective data processing unit) may input control commands, and the control unit 150 may output to the user information indicative of the performance of the fluid pump 160. Moreover, the control unit 150 is coupled to a database 76 which is accessible by the control unit 150 for reading control information such as curves indicating a drive performance for driving the base drive unit 170 and the piezomechanism 72. As can be taken from Fig. 2, the control unit 150 may receive measurement data from the flow sensor 58 and may control the fluid inlet valve 52 as well as the fluid outlet valve 56 to coordinate switching of these valves 52, 56 with the reciprocation of the piston 1.

[0085] In the following, it will be described how the fluid pump 160 can be operated so as to provide a constant pressure value during a duty cycle of the fluid pump 160.

[0086] The flow sensor 58 is configured for sensing an actual flow value directly downstream the fluid outlet valve 56, so that an actual pressure profile (i.e. a pressure dependency over time) may be detected by the flow sensor 58 and supplied to the control unit 150. Additionally or alternatively, it is possible to provide a flow sensor for sensing an actual flow value directly upstream the fluid outlet valve 56. Furthermore, a predefined target characteristic of the pressure profile may be stored in the database 76. Corresponding data may be accessed by the control unit in the database 76. The control unit 150 may therefore use and process this information to control the base drive unit 170 and the piezomechanism 72 so that the actual pressure profile as detected by the flow sensor 58 can be brought in accordance with the predefined target characteristic as stored in the database 76.

Hence, every pressure artifact may therefore be suppressed.

[0087] The control unit 150 may be adapted for basically real time processing in view of the fast sensor arrangement and the fast transmission of signals. This may allow for a more precise control as compared to a predefined processing by stored data or a cam mechanism. Thus, it is possible to rapidly react on actually measured values, allowing for addressing temporary challenges such as a fluctuation in the quality of solvents, artifacts due to gas bubbles, etc. [0088] As will be described below referring to Fig. 6 in more detail, it may happen that the fluid pump 160 shows a characteristic periodic sequence of pressure ripples which result from the coordinated switching of the valves 52, 56 as well as from the reciprocating motion of the piston 1. If such a periodic pattern of artifacts can be considered as a typical behavior of the fluid pump 160, the pressure sensor 58 may be omitted, since a corresponding control curve for suppressing or eliminating such periodic pressure ripples may be stored in the database 76. Such a scheme may also be denoted as a compensation scheme.

[0089] Such a compensation procedure may be performed by activation of the piezomechanism 72, if desired or required. Hence, a main component of the reciprocation of the piston 1 may be provided by the base drive unit 170, whereas the piezo drive 72 provides an additional correction.

[0090] Fig. 3 shows a fluid pump 300 according to another exemplary embodiment of the invention.

[0091] In Fig. 3, a first fluid container 302 including a first solvent and a second fluid container 304 including a second solvent is shown. The first solvent from the first container 302 and the second solvent from the second container 304 are mixed and supplied via the inlet valve 52 into the pumping chamber 9 delimited by the piston 1 and the cylinder 3.

[0092] In the shown embodiment, an example for the constitution of a piezomechanism is shown. A structure of piezoelectric material, denoted with reference numeral 306, can be actuated (i.e. elongated or contracted along a direction 330) by applying a corresponding drive voltage as indicated by an electric voltage source 308. Electric voltage source 308 is controlled by the control unit 150.

A coupling plate 310 may couple the piezoelectric structure 306 via a ruby ball 8 to coupling member 6.

[0093] In addition to the piezoelectric actuation, a crankshaft mechanism is shown as a base drive unit. A motor 310 such as an electromotor which is operated under control of the control unit 150 rotates a cylinder or disk-like rotor 312. A connection rod 316 is eccentrically mounted on the rotor 31 2 so as to translate the rotation of the rotor 312 into a linear reciprocation of the piston 1. Again, the -20 -eccentric drive mechanism 310, 312, 316 functions as a base drive unit with a superposed reciprocation component of the piezoelectric drive 306, 308.

[0094] Fig. 4 shows an enlarged view 400 of a force transmission between a piezo drive 402 (operated under control of control unit 150) and a piston 1 of a fluid pump according to an embodiment of the invention. Piezoelectric stacks 402 are shown which can be activated by a voltage source (not shown). Piezoelectric stacks 402 are arranged between a respective base plate 406 (on which a bias force F is applied) and a force transmission rod 408. Due to the alternating elongation and contraction of the piezoelectric stacks 402, a reciprocating force may be transmitted from force transmission rod 408 via the ball 8 and the coupling element 6 to the piston 1.

[0095] In the following, referring to Fig. 5, a fluid pump 510 according to another exemplary embodiment of the invention will be explained. In contrast to the embodiments shown in Fig. 2 and Fig. 3, the fluid pump 510 comprises a pressure sensor 512 instead of a flow sensor 58. However, a flow sensor can be implemented in Fig. 5 as well.

[0096] According to Fig. 5, a piezomechanism 514 is the only drive mechanism for driving the piston 1. In the shown embodiment, four individually activatable and controllable piezoelectric elements 306 are shown in a cascade or serially coupled arrangement. In contrast to the cascade arrangement of four piezoelectric drives 306, it is also possible to use a single piezoelectric drive. However, to achieve large stroke widths, the skilled person will understand that the use of a number of piezoelectric drives 306 adding their individual contributions is advantageous.

[0097] Although the embodiments shown in the above described figures include a ball 8, such a ball may be omitted in other embodiments to directly couple a drive with a piezomechanism.

[0098] Fig. 6 shows a diagram 500 having an abscissa 502 along which the time is plotted. Along an ordinate 504 a pressure value measured at a position of the pressure sensor 512 is shown. As can be taken from the pressure curve shown in diagram 500, a periodic arrangement of pressure ripples 506 alternates with constant pressure intervals 508. For a proper performance of a chromatography -21 -separation, it is desired to have a constant pressure over the entire operation time, as obtained in the sections 508. However, due to switching of valves 52, 56 and due to motion reversal of the piston 1 in the chamber 3, the arrangement of ripples 506 may be symmetric, i.e. equidistant. It may also be positive or negative or equidistant if the low range is constant over the time interval, otherwise they can be variable.

[0099] Therefore, a compensation scheme as illustrated in diagram 600 can be used to compensate for such artifacts 506. Along an ordinate 602 of the diagram 600, a voltage to be applied to a piezoelectric drive 306 (having one or more for instance via serial bus driven piezoelements) is shown. Thus, by applying compensation pulses 604 which may, for instance, have an inverse characteristic as compared to the pressure ripples 506, a proper compensation may be achieved.

The compensation scheme shown in the diagram 600 may be used for instance with an embodiment such as shown in Fig. 2 or Fig. 3 where the corresponding base drive unit is driven to provide a main reciprocation component of the piston 1, whereas the compensation pulses 604 may be applied to the piezoelectric drive 72, 306 to achieve a constant pumping pressure, i.e. a target pressure behavior.

[001001 Still referring to the embodiment of Fig. 6, it may here be dispensable to permanently measure the pressure with a pressure sensor 502 or the like. In contrast to this, one may rely on the periodicity of the appearing pressure ripples 506 and may therefore apply the compensation scheme shown in Fig. 6 which may be stored in database 76.

[00101] Alternatively, as can be taken from Fig. 7, it may also happen that, in addition to the periodic pressure ripples 506 originating from switching of the valves 52, 56, aperiodic pressure ripples 702, 704 may occur which may have any other, for instance external, origin. This is shown in a diagram 700 which is similar to diagram 500. The aperiodic ripples 702, 704 may arise from singular distortions within the pump fluid which may be difficult to predict. In such a scenario, if a compensation of such aperiodic pressure ripples 702, 704 is desired as well, a permanent measurement of the pressure p by pressure sensor 502 can be performed, and the present pressure value can be supplied to the control unit 150.

In such an embodiment, the fast operating piezoelectric mechanisms may allow to suppress such aperiodic pressure ripples 702, 704. If the pressure sensor 502 is -22 -about to detect a pressure ripple 702, 704, the control unit 150 may directly calculate a correction signal applied to a piezomechanism 306 to provide a compensating stroke contribution. This can be a positive or negative contribution, as shown as a compensation scheme in the diagram 750 which corresponds to diagram 600. In addition to the regular compensation pulses 604, aperiodic compensation pulses 712, 714 may be added.

[00102] In an embodiment, a piezo driven syringe may be used. Hence, a micro-patterned or micro-structured system with a syringe as injector or as pump direct or indirect driven piston may be used for low flow applications. This may further contribute to a miniaturization of the system.

[001031 In an embodiment, cascaded systems, particularly cascades of piezomechanisms e.g. serially or parallelly combined may be implemented.

[00104] Fig. 8 shows a fluid pump 800 according to another exemplary embodiment of the invention. Fluid pump 800 is shown only partially in Fig. 8 but has a very similar construction as fluid pump 510 shown in Fig. 5. However, in contrast to Fig. 5, fluid pump 800 has a direct coupling architecture and is therefore free of balls 8. Furthermore, fluid pump 800 has an arrangement of two serially coupled piston pump systems which can be controlled by the same or by different control units for ripple suppression.

[001051 Fig. 9 shows a fluid pump 900 according to another exemplary embodiment of the invention. Fluid pump 900 is shown only partially in Fig. 9 but has a very similar construction as fluid pump 510 shown in Fig. 5. However, in contrast to Fig. 5, fluid pump 900 has a direct coupling architecture and is therefore free of a ball 8. Furthermore, and in contrast to Fig. 8, fluid pump 900 has two groups 904, 906 of arrangements of two serially coupled piston pump systems each which can be controlled by the same or by different control units for ripple suppression. Fluid pumped by the groups 904, 906 can then be mixed at a mixing point 902.

[00106] It should be noted that the term "comprising" does not exclude other elements or features and the "a" or "an" does not exclude a plurality. Also elements described in association with different embodiments may be combined. It should -23 -also be noted that reference signs in the claims shall not be construed as limiting the scope of the claims.

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Claims (29)

1. CLAIMS1. A fluid pump for use in a fluid separation system for separating compounds of a fluidic sample in a mobile phase, the fluid pump comprising: a reciprocatable piston configured for moving the mobile phase; a pump drive configured for driving the reciprocatable piston; a control unit configured for controlling the pump drive so that pressure ripples in a pressure profile of the fluid pump are at least partially compensated to thereby bring the pressure profile in accordance with a predefined target characteristic.
2. 2. The fluid pump of the preceding claim, wherein the pump drive is configured for driving the reciprocatable piston using a piezomechanism.
3. 3. The fluid pump of claim 1 or any one of the above claims or claim 11, comprising a sensor configured for sensing an actual pressure profile of the fluid pump; wherein the control unit is configured for controlling the pump drive so that the actual pressure profile is brought in accordance with the predefined target characteristic.
4. 4. The fluid pump of the preceding claim, wherein the sensor is configured as one of the group consisting of a flow sensor and a pressure sensor.
5. 5. The fluid pump of claim 1 or any one of the above claims or claim 11, comprising a storage unit accessible by the control unit and storing data being indicative of a compensation scheme for controlling the pump drive so that a characteristic pressure profile of the fluid pump is brought in accordance with the predefined target characteristic.

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6. 6. The fluid pump of claim 1 or any one of the above claims or claim 11, wherein the pressure ripples are ripples of a periodic pattern in the pressure profile of the fluid pump.
7. 7. The fluid pump of claim 1 or any one of the above claims or claim 11, comprising a fluid inlet valve arranged upstream with respect to a housing of the piston and/or comprising a fluid outlet valve arranged downstream with respect to the housing of the piston, the fluid inlet valve and/or the fluid outlet valve being switchable synchronized with a reciprocation of the piston and causing the pressure ripples.
8. 8. The fluid pump of claim 3 and the preceding claim, wherein the sensor is arranged upstream or downstream, particularly directly upstream or downstream, the fluid outlet valve.
9. 9. The fluid pump of claim 1 or any one of the above claims or claim 11, wherein the predefined target characteristic is free of the pressure ripples, particularly is a pressure value being constant over time during at least a part of a procedure of separating compounds of the fluidic sample in the mobile phase.
10. 10. A fluid pump for use in a fluid separation system for separating compounds of a flu idic sample in a mobile phase, the fluid pump comprising: a reciprocatable piston configured for moving the mobile phase; a pump drive configured for driving the reciprocatable piston using a piezomechanism.
11. 11. The fluid pump of the preceding claim, comprising a control unit configured for controlling the pump drive so that pressure ripples in a pressure profile of the fluid pump are at least partially compensated to thereby bring the pressure profile in accordance with a predefi ned target characteristic.

    -26 -
12. 12. The fluid pump of claim 10 or any one of the above claims or claim 2, wherein the reciprocatable piston is exclusively driven by the piezomechanism.
13. 13. The fluid pump of claim 10 or any one of the above claims or claim 2, wherein the pump drive comprises a single piezo drive.
14. 14. The fluid pump of claim 10 or any one of the above claims or claim 2, wherein the pump drive comprises a plurality of piezo drives cooperating for mutually driving the reciprocatable piston, particularly comprises a cascade of piezo drives.
15. 15. The fluid pump of claim 10 or any one of the above claims or claim 2, wherein the pump drive comprises a base drive unit and a piezo drive unit, the base drive unit being configured for providing a base drive component for driving the piston, and the piezo drive unit being configured for providing an additional drive component for driving the piston.
16. 16. The fluid pump of the preceding claim, wherein the base drive component has a larger amplitude than the additional drive component.
17. 17. The fluid pump of claim 15 or any one of the above claims, wherein the control unit is configured for activating the additional drive component upon determining a discrepancy between an actual pressure profile of the fluid pump and a predefined target characteristic of the pressure profile.
18. 18. The fluid pump of claim 15 or any one of the above claims, wherein the base drive unit comprises at least one of the group consisting of an eccentric drive mechanism and a ball-screw mechanism.
19. 19. The fluid pump of claim 15 or any one of the above claims, -27 -wherein the additional drive component is configured to provide at least one of the group consisting of a fine adjustment of driving the reciprocatable piston, and a correction of driving the reciprocatable piston.
20. 20. The fluid pump of claim 15 or any one of the above claims, wherein the additional drive component is arranged spatially between the reciprocatable piston and the base drive unit.
21. 21. The fluid pump of claim 10 or any one of the above claims or claim 1, wherein the fluid pump is configured as a nanopump.
22. 22. The fluid pump of claim 10 or any one of the above claims or claim 1, wherein a stroke width of the piston is less than 7 mm, particularly less than 3 mm.
23. 23. The fluid pump of claim 10 or any one of the above claims or claim 1, providing a flow rate of the mobile phase of less than 500 nm/mm, particularly less than 200 nm/mm.
24. 24. The fluid pump of claim 10 or any one of the above claims or claim 2, comprising a force transmission body, particularly a force transmission ball, arranged between the reciprocatable piston and the piezomechanism.
25. 25. The fluid pump of claim 10 or any one of the above claims or claim 2, wherein the piezomechanism is arranged to directly act on the reciprocatable piston.
26. 26. A fluid separation system for separating compounds of a fluidic sample in a mobile phase, the fluid separation system comprising: a fluid pump according to any one of the above claims configured to drive the mobile phase through the fluid separation system; a separation unit, particularly a chromatographic column, adapted for -28 -separating compounds of the fluidic sample in the mobile phase.
27. 27. The fluid separation system of the preceding claim, further comprising at least one of the following features: the fluid separation system comprises a piezo driven syringe for supplying a fluid; the fluid separation system comprises a detector adapted to detect separated compounds of the fluidic sample; the fluid separation system comprises a collection unit adapted to collect separated compounds of the fluidic sample; the fluid separation system comprises a data processing unit adapted to process data received from any component of the fluid separation system; the fluid separation system comprises a degassing apparatus for degassing the mobile phase; the fluid separation system is adapted as a chromatographic separation system, particularly as a HPLC.
28. 28. A method of operating a fluid pump for use in a fluid separation system for separating compounds of a fluidic sample in a mobile phase, the method comprising: driving the reciprocatable piston to reciprocate for moving the mobile phase; controlling the driving so that pressure ripples in a pressure profile of the fluid pump are at least partially compensated to thereby bring the pressure profile in accordance with a predefined target characteristic.
29. 29. A method of operating a fluid pump for use in a fluid separation system for separating compounds of a fluidic sample in a mobile phase, the method comprising: driving a reciprocatable piston using a piezornechanism for moving the mobile phase.-29 - *::r: INTELLECTUAL . ... PROPERTY OFFICE Application No: GB 1011054.2 Examiner: James Paddock Claims searched: 1 and 28. Date of search: 17 November 2010 Patents Act 1977: Search Report under Section 17 Documents considered to be relevant: Category Relevant Identity of document and passage or figure of particular relevance to claims X 1,3,4,6-GB2189555 A 9,22,23,2 JEOL See Figure 9 and para bridging pages 4 and 5. Dual piston pump 6-28 for chromatography in which the upstream pump is adjusted to remove ripples in the aggregate output.X X:1,3-EP0810370 A 9,2 1-GRACO See the claims and Figure 2. General pump with compensatory 23,28 movements imposed on base piston motion.X 1,3-W097/32128 A 6,8,9,22-PHARMACIA See claim 11. An HPLC pump controlled to produce a 24,26-28 pulseless output.X 1,3-9,22-EP0050296 A 24,26-28 NIKKISO See Figure 4. and page 2, line 20. Pulsationless pump uses inverted pulsation signal as driver input. Pulsation is valve operating artefact.X 1,5-9,22-EP0303220 A 23,28 HITACHI See Claim 1 and figs. 4a,b. Low pulsation pump where errors leading to pulsation are corrected by adjusting the drive. Pressure proportional to flow rate.X 1,3-EP0260764 A 6,8,9,22-PHILIPS See Claim 1. Chromatograph system with advance or retard of 24,26-28 piston timing to compensate for ripples.Categories: X Document indicating lack of novelty or inventive A Document indicating technological background and/or state step of the art.Y Document indicating lack of inventive step if P Document published on or after the declared priority date but combined with one or more other documents of before the filing date of this invention.same category.& Member of the same patent family E Patent document published on or after, but with priority date earlier than, the filing date of this application.Field of Search:Search of GB, EP, WO & US patent documents classified in the following areas of the UKCX: Worldwide search of patent documents classified in the following areas of the IPC FO4B; GO1N The following online and other databases have been used in the preparation of this search report Intellectual Property Office is an operating name of the Patent Office www.ipo.gov.uk *.:r: INTELLECTUAL . ... PROPERTY OFFICE WPI, EPODOC, TXTE International Classification: Subclass Subgroup Valid From FO4B 0011/00 01/01/2006 FO4B 0049/06 01/01/2006 GO1N 0030/32 01/01/2006 GO1N 0030/36 01/01/2006 GO1N 0030/32 01/01/2006 Intellectual Property Office is an operating name of the Patent Office www.ipo.gov.uk *::r: INTELLECTUAL . ... PROPERTY OFFICE Application No: GB 1011054.2 Examiner: James Paddock Claims searched: 10-27,29 Date of search: 1 June 2011 Patents Act 1977 Further Search Report under Section 17 Documents considered to be relevant: Category Relevant Identity of document and passage or figure of particular relevance to claims X 10,13,15, US2005/061722 A 16,18-23, HITACHI See Figures 1 and 2. Liquid chromatography pump with 25-27,29 combined ball screw and piezo actuator driving piston.X 10,12,13, EP2107241 A 21-THERMO FISCHER See Figure 1 and para 51. Piezo drive system for 24,26,27, liquid chromatography piston pump.X 10,12,13, JP06093974 A 21-23,25-HITACHI See the Figures and EPODOC abstract. Chromatograph low 27,29 ripp'e pump with piezoelectric driver.X 10.12,13, U52005/095145 A 2 1-23,25-HITACHI See Figure 1 and para 41. Piezoelectric plunger drive in 27,29 chromatography pump.Categories: X Document indicating lack of novelty or inventive A Document indicating technological background and/or state step of the art.Y Document indicating lack of inventive step if P Document published on or after the declared priority date but combined with one or more other documents of before the filing date of this invention.same category.& Member of the same patent family E Patent document published on or after, hut with priority date earlier than, the filing date of this application.Field of Search:Search of GB, EP, WO & US patent docjments classified in the following areas of the UKCX Worldwide search of patent documents classified in the following areas of the IPC FO4B; GO1N The following online and other databases have been used in the preparation of this search report WPI, EPODOC, TXTE International Classification: Subclass Subgroup Valid From FO4B 0011/00 01/01/2006 FO4B 0049/06 01/01/2006 Intellectual Property Office is an operating name of the Patent Office www.ipo.gov.uk *.:r: INTELLECTUAL . ... PROPERTY OFFICE Subclass Subgroup Valid From GO1N 0030/32 01/01/2006 GO1N 0030/36 01/01/2006 GO1N 0030/32 01/01/2006 Intellectual Property Office is an operating name of the Patent Office www.ipo.gov.uk