Sample separation apparatus with fluid drive unit decoupling

Abstract

A sample separation apparatus (10) with fluid drive unit decoupling for separating a fluid sample, the sample separation apparatus (10) comprising: i) fluid drive means (20) comprising a first fluid drive unit (102) and a second fluid drive unit (104) for driving a mobile phase along a flow path (108) to a sample separation unit (30); ii) a sample containing chamber (106) configured to contain a fluid sample and configured to be selectively fluidly coupled or fluidly decoupled from the flow path (108); and iii) a control unit (70) configured to control respective operation of the fluid drive units (102, 104) and to control fluid decoupling of the second fluid drive unit (104) from the flow path (108) in a decoupling mode of operation of the sample separation apparatus (10), the control unit (70) is further configured to control, in a decoupled mode of operation, the decoupled second fluid drive unit (104) to: a) fluidly couple to the sample receiving chamber (106), and b) ingress the sample into the sample receiving chamber (106).

Description

Technical Field

[0001] The present disclosure relates to a sample separation device for separating a fluid sample, wherein the sample separation device comprises a fluid driving device having a first fluid driving unit and a second fluid driving unit for driving a mobile phase along a flow path to a sample separation unit. The sample separation device further comprises a control unit configured to control the corresponding operation of the fluid driving unit and control the decoupling of the second fluid driving unit from the fluid of the flow path in a decoupling operation mode. The present disclosure also relates to a method for operating the sample separation device. Background Art

[0002] An analytical device is provided to analyze the sample, for example using a sample separation apparatus.

[0003] For example, for liquid separation in a chromatographic system, a mobile phase comprising a sample fluid (e.g., a chemical or biological mixture) with the complexes to be separated is driven through a stationary phase (e.g., a chromatographic column packing, etc.), thereby separating the different complexes of the sample fluid, which can then be identified. The term complex as used herein shall encompass complexes that may contain one or more different components.

[0004] A mobile phase, which typically includes one or more solvents, is pumped through a chromatographic column containing a packing medium (also called a filler material or stationary phase), usually at high pressure. As the sample is carried through the column by the liquid stream, different complexes, each with a different affinity for the packing medium, move through the column at different speeds. Those complexes that have a greater affinity for the stationary phase move slower through the column than those with a lesser affinity, and this speed difference causes the complexes to separate from each other as they pass through the column. The stationary phase is subjected to a mechanical force generated, in particular, by a hydraulic pump, which typically pumps the mobile phase from an upstream connection of the column to a downstream connection of the column. Due to the flow, a relatively high pressure drop is generated across the column, depending on the physical properties of the stationary phase and the mobile phase.

[0005] The mobile phase with the separated complexes leaves the column and passes through a detector, which records and / or identifies the molecules, for example by spectrophotometric absorbance measurements. A two-dimensional graph of the detector measurements versus elution time or volume, called a chromatogram, can be plotted, and the complexes can be identified from the chromatogram. For each complex, the chromatogram shows a separate curve feature, also called a "peak."

[0006] Therefore, precisely controlled fluid flow through the sample separation system is essential, especially for HPLC systems. This requires (in current HPLC systems) a pump that can provide this high flow accuracy and, in turn, low backpressure pulsation levels at the (potentially variable) flow resistance of the other components of the HPLC system. This is typically achieved by using a dual piston pump design, whereby each piston is driven independently by active control feedback.

[0007] Furthermore, additional pumping devices (metering devices) may be used to meter the sample to be analyzed / separated.In conventional designs, metering devices are always included in the fluid path of the HPLC system, except during the sample extraction and preparation phases.

[0008] However, the metering devices and separate piston drives used in modern HPLC systems are expensive components that must be installed and maintained in a costly and laborious manner. Therefore, metering devices have traditionally been used only during the sample extraction and preparation phases. Summary of the invention

[0009] It may be desirable to operate the sample separation device in a (cost) efficient manner, in particular with regard to the pump system. The independent claims describe a sample separation device and a method. Further embodiments are described by the dependent claims.

[0010] According to one aspect of the present disclosure, a sample separation device (e.g., HPLC) for separating a fluid sample is described, the sample separation device comprising:

[0011] i) a fluid driving device (e.g., two or more pumps), comprising a first fluid driving unit (including a first piston) and a second fluid driving unit (including a second piston) for driving a mobile phase along a flow path to a sample separation unit (e.g., a chromatographic column);

[0012] ii) a sample holding cavity (e.g. a sample needle and / or a sample loop) configured to hold a fluid sample and in particular configured to be selectively fluidically coupled to the flow path (e.g. for introduction of the held sample) or fluidically decoupled from the flow path (e.g. during sample intake) (in the example, the sample holding cavity is inseparably connected to the second fluid drive and thus they are always connected / disconnected from the flow path together); and

[0013] iii) a control unit (control device, control system, such as a processor, etc.), which is configured to control the corresponding operation of the fluid drive unit, and control the fluid decoupling (fluid disconnection) of the second fluid drive unit from the flow path (such as through one or more switching valves) in the decoupling operation mode of the sample separation device, wherein the control unit is further configured to control the decoupled second fluid drive unit in the decoupling operation mode to

[0014] a) fluidly coupled (fluidically connected) to the sample holding chamber, and

[0015] b) Taking the sample into the sample holding chamber (using the second fluid drive unit as a metering device).

[0016] According to another aspect of the present disclosure, a method of operating a sample separation device (e.g. as described above) is described, the method comprising:

[0017] i) driving the mobile phase along the flow path to the sample separation unit by a fluid driving device, wherein the fluid driving device comprises a first fluid driving unit and a second fluid driving unit;

[0018] ii) receiving a fluid sample in a sample receiving chamber, and in particular selectively coupling the sample receiving chamber to a flow path or decoupling the sample receiving chamber from the flow path;

[0019] iii) decoupling the second fluid drive unit from the flow path fluid in a decoupled operating mode of the sample separation device,

[0020] iv) in a decoupled operating mode, fluidically coupling the decoupled second fluid drive unit to the sample holding chamber, and

[0021] v) (through the second fluid driving unit) taking the sample into the sample holding chamber.

[0022] According to another aspect of the present disclosure, a use (method of use) of a fluid drive unit of a fluid drive device of a chromatography device is described, wherein the fluid drive unit decoupled from a separation flow path is used as a metering device to trigger the intake of a fluid sample into a sample holding chamber.

[0023] In the context of this paper, the term "fluid sample" may particularly denote any liquid and / or gaseous medium, optionally also comprising solid particles to be analyzed. Such a fluid sample may include a variety of fractions of molecules or particles to be separated, such as small mass molecules or large mass biomolecules such as proteins. Separating a fluid sample into fractions involves certain separation criteria (such as mass, volume, chemical properties, etc.) according to which the separation is performed.

[0024] In the context of this paper, the term "mobile phase" can particularly represent any liquid and / or fluid (e.g., supercritical) medium that can be used as a fluid carrier of a fluid sample during separation. The mobile phase can be a solvent or a solvent composition (e.g., consisting of water and an organic solvent such as ethanol or acetonitrile). In the isocratic separation mode of a liquid chromatographic device, the mobile phase can have a composition that is constant over time. However, in a gradient mode, the composition of the mobile phase can change over time, particularly to desorb the fraction of the stationary phase that has previously been adsorbed to the separation unit of the fluid sample.

[0025] In the present context, the term "sample separation device" may particularly denote any device capable of separating different fractions of a fluid sample by applying a certain separation technique, particularly liquid chromatography.

[0026] The term "separation unit" may particularly denote a fluidic member through which a fluid sample is conveyed and which is configured such that when the fluid sample is directed through the separation unit, the fluid sample will separate into different groups of molecules or particles. An example of a separation unit is a liquid chromatography column, which is capable of collecting or retaining and selectively releasing different fractions of a fluid sample.

[0027] In the context of the present application, the term "sample holding chamber" may particularly refer to a defined portion or section of a flow path, a fluid conduit, or a fluid component (such as a fluid valve, etc.) in which a predetermined amount of fluid can be at least temporarily held. In an embodiment, the fluid holding chamber may be a sample loop (e.g., connected to a port fluid of a modulating valve). The fluid holding chamber may be at least temporarily decoupled from the flow path or main path fluid. By means of a switching mechanism, the sample holding chamber may first be coupled to a certain position in the sample separation device, and later alternatively or additionally coupled to a different position in the sample separation device.

[0028] In the context of this article, the term "fluid drive unit" may particularly denote a device configured to drive a fluid along a flow path. In a preferred embodiment, the fluid drive unit may be implemented as one or more pump units. In a basic example, the fluid drive unit may include a pump unit having a piston and a corresponding piston cylinder (pump chamber) (and a corresponding motion source, such as a motor, etc.). In another example, the fluid drive unit may include two (or more) pump units, such as two piston cylinders (e.g., double pumps) with corresponding pistons (and a common motion source). In the example, the fluid drive unit may be described as a pumping device, which includes - in the case of a piston or plunger pump - one or more pump cylinders (pump units) with a piston or plunger. In particular, the pump unit of the fluid drive unit may be driven by a single motion / energy source, such as a single motor. Accordingly, in the example, the pump unit (e.g., piston / cylinder pair) of the fluid drive unit may be mechanically dependent and may not be independently driven (due to its mechanical coupling). Therefore, the term "fluid drive unit" may, for example, refer to a single piston drive and a coupled double piston drive.

[0029] In this document, the term "coupled fluid drive unit" can be understood as driving two or more pumps through the same energy source (motor) and / or coupling them via gears or other means. However, the coupling can be such that the piston positions are mechanically coupled and cannot be changed independently (mechanically dependent on each other).

[0030] In this context, the term “flow path” is to be understood as a fluid path which (in the current switching and configuration state of the separation device) participates in the transport of the fluid from the pump drive unit to the sample separation unit.

[0031] According to an exemplary embodiment, the present disclosure may be based on the following idea: when the fluid drive device of the sample separation device includes at least two fluid drive units (such as pump pistons), the sample separation device (especially HPLC) can be operated in a particularly (cost) efficient manner, and wherein the system (for example, by controlling a valve controlled by a control unit) is configured to temporarily decouple the second fluid drive unit from the first fluid drive unit, and instead couple the second fluid drive unit to a sample holding chamber (such as a sample loop), so that the sample can be taken into the sample holding chamber through the second fluid drive unit.

[0032] By this mode of operation, the conventional additional metering device for taking the sample into the sample holding chamber can be eliminated. In this way, the high material and maintenance costs (and space requirements) for the metering device can be saved, while the sample separation device can still operate in an efficient and reliable manner.

[0033] In other words, the present disclosure functionally integrates the fluid drive unit (pump drive) and the metering device of the current HPLC system into or as a single device, and one of the pistons (fluid drive unit) of the pump can also be engaged as a metering device (or, conversely, the metering device of the sampler can be engaged as a pump drive). Therefore, the number of (electric) pump drives in the system can be reduced by (at least) one. Since the metering task will fully occupy the corresponding fluid drive unit during sample extraction and injection, the fluid connection can be switched by a valve to connect parts of the fluid path according to the needs of a specific function.

[0034] The disclosure can realize the reduction of complexity and cost of sample separation system and / or improve performance with low cost or no additional cost.Compared with previous methods, the disclosure can need fewer parts, and reuse the existing subunits of sample separation equipment to perform multiple tasks, rather than each subunit performing a single task.Therefore, compared with current architecture / operating mode, the disclosure can provide significant cost saving potential.

[0035] Exemplary Embodiments

[0036] In an embodiment, in the decoupled operation mode, the first fluid drive unit is coupled to the separation unit. The first fluid drive unit can maintain fluid flow to the sample separation unit without injecting a sample. Therefore, high pressure can be efficiently maintained and artifacts can flow out of the flow path.

[0037] In an embodiment, in the decoupled operation mode, the second fluid drive unit is decoupled from the sample separation unit. Thus, the second fluid drive unit can be used as a metering device and take in a sample at normal pressure / ambient pressure. This can be achieved by fluidically decoupling or pressure decoupling the second fluid drive unit from the high pressure flow path, for example by disconnecting the fluid connection of the second fluid drive unit from the first fluid drive unit and from the sample separation unit and establishing a fluid connection between the first fluid drive unit and the sample separation unit.

[0038] In an embodiment, in the decoupled operation mode, the second drive unit operates as a metering device, in particular a metering pump, to draw the fluid sample from the sample container (e.g., a vial), preferably into the sample holding chamber. When the second drive unit is configured as a pump (e.g., with a piston), it can efficiently and reliably complete the task of drawing a specific amount of fluid sample into the sample holding chamber.

[0039] In an embodiment, the control unit is further configured to, under the decoupling operation mode, at least partially or temporarily block the sample flow path from the second fluid drive unit through the sample holding unit. The sample flow path may include the second fluid drive unit, the sample holding chamber, the fluid switching valve, the needle seat and the needle. In addition, only the section of the sample flow path rather than the entire path can be blocked. The blocking may be particularly downstream of the sample holding unit along the process direction. Another blocking point may be located upstream of the second fluid drive unit along the process direction. When the second fluid drive unit (through the pumping process) provides pressure and the sample flow path (e.g., at the switching valve) is (at least partially) blocked, the fluid sample can be compressed. This pre-compressed sample can be injected into the high pressure flow path in an efficient and robust manner. In an example, the pre-compressed sample can be disconnected (isolated) by fluid in the fluid blocking section of the fluid flow path, and is stored in the section for a period of time in a pre-compressed state before it is injected into the high pressure flow path.

[0040] In an embodiment, the control unit is further configured to control (e.g., by one or more switching valves) the (fluid connection) coupling between the first fluid drive unit and the second fluid drive unit in a coupled operating mode, wherein the first fluid drive unit and the second fluid drive unit are particularly fluidically coupled to each other in series or in parallel. The coupled operating mode may correspond to the normal operating mode of the sample separation device (HPLC): a pump with two pistons (two pump units) is applied to pump the mobile phase to the sample separation unit. The flow of the mobile phase thus passes through the sample holding chamber in order to take the fluid sample contained in the high pressure path. Therefore, the described sample separation device can efficiently switch between the normal operating mode and the decoupling bypass operating mode, wherein the second drive unit operates as a metering device.

[0041] In an embodiment, in the coupled operating mode, the first fluid drive unit and the second fluid drive unit are pressure-coupled to each other. In other words, both pump drives are fluidically connected and operate in the high pressure domain.

[0042] In an embodiment, in the decoupled operation mode, the first fluid drive unit and the second fluid drive unit are pressure-decoupled from each other, in particular wherein the first fluid drive unit is coupled in the high-pressure path and / or wherein the second fluid drive unit is coupled in the low-pressure path. The pressure decoupling of the second fluid drive unit can achieve efficient sample intake.

[0043] In an embodiment, in the coupled operating mode, the mobile phase, in particular the solvent, is drawn by the first fluid drive unit, in particular from a solvent container, and then flows to the second fluid drive unit. In this normal operating mode, the first fluid drive unit is arranged upstream of the second fluid drive unit in the process direction.

[0044] In an embodiment, in a coupled operation mode, the first fluid drive unit and the second fluid drive unit (or the first pump unit and the second pump unit) are connected in parallel (or in series) to simultaneously or alternately deliver the solvent from the solvent container to the high-pressure flow path, and the high-pressure flow path may include a solvent holding chamber so that the sample contained therein can be taken up and transported toward the sample separation unit together with the fluid flow.

[0045] In an embodiment, in the coupled operating mode, the mobile phase flows through the sample holding unit downstream of the fluid drive device in the process direction, thereby picking up the fluid sample held in the sample holding unit.

[0046] In an embodiment, the sample holding unit is configured as one of a sample loop, a multi-sample storage (a "sample parking platform", such as several sample holding units coupled in parallel), a sampler, an automatic sampler, and an injection needle. Based on the desired application, the fluid sample can be contained in a variety of different cavities, many of which are established in the field of chromatography. Therefore, the present disclosure can be directly implemented in multiple established applications. There may also be a combination of two or more sample holding cavities. For example, the sample can be taken by a sample needle as a first sample holding cavity and then transported to a sample loop as a second sample holding cavity. In any case, the second fluid drive unit can be directly applied (by metering) to take the sample into the sample cavity, such as drawing the sample into a needle. The sample can then flow to or flow into the sample loop at least partially.

[0047] In an embodiment, the first fluid drive unit and / or the second drive unit comprises two or more pump units (the pump units for example comprise pistons / cylinders) connected to a common motion source, in particular a motor. In an embodiment, the two or more pump units are mechanically dependent on each other (mechanically coupled and not independent in motion).

[0048] In an embodiment, the fluid drive device is configured as a chromatographic pump, which includes two (or more) pump pistons (pump units) in a coupled mode, such as an isocratic parallel pump, an isocratic series pump, a low-pressure mixed series or parallel pump (also known as a quaternary pump), a high-pressure mixed multi-channel pump, such as a binary pump with a parallel or series drive configuration in each pump channel. In an embodiment, the first fluid drive unit is arranged upstream of the second fluid drive unit in the process direction. In an embodiment, the first fluid drive unit and the second fluid drive unit are fluidically coupled to each other in series or in parallel. Therefore, multiple established pump architectures can be directly applied.

[0049] In an embodiment, the sample separation device further comprises a switching unit, in particular a fluid valve (e.g. a rotary valve, a shear valve or a set of shut-off valves, e.g. a high-pressure needle valve) arranged between the first fluid drive unit and the second fluid drive unit in the process direction (see also Fig. 9 and Fig.10 ). The switching unit can be coupled to the control unit, wherein the control unit is then configured to switch between the coupled operating mode and the decoupled operating mode via the switching unit. Switching valves are widely established in the field of liquid chromatography. Exemplary embodiments are as follows Figures 2 to 4 shown.

[0050] In an embodiment, the sample separation device does not have a dedicated metering device, particularly a metering pump. As mentioned above, significant installation and maintenance costs can be saved in this way. In addition, less operating space can be required. It should be understood that although the second fluid drive unit can be located near or inside the sampler or automatic sampler, and can be considered as a metering unit, it can be configured to realize the function of the fluid driver of the chromatographic pump. Therefore, the following two viewpoints are equivalent, that is: i) eliminate metering device from the sampler, and its function can be realized by a fluid driver from the chromatographic pump, and ii) eliminate a fluid driver from the chromatographic pump, and its function can be transferred to metering device.

[0051] In an embodiment, the sample separation device further comprises a damping device, in particular a passive damping device, for damping flow pulsations (pressure spikes) in the flow path. In particular, in the bypass operation mode, the damping device can compensate for the decoupled second fluid drive unit and maintain a stable flow from the first fluid drive unit to the sample separation unit.

[0052] In the context of this article, the term "damping device" may particularly refer to a device suitable for implementing a damping function relative to a fluid flow path of a sample separation device. In the most basic example, the damping device may include a cavity through which a solvent can flow. In this way, damping can already be achieved. Preferably, the cavity is capable of withstanding a high pressure of, for example, 1000 bar of the fluid. In a more complex example, an elastic element such as a membrane may constitute a wall of the fluid cavity. The outer side of the membrane (relative to the solvent flow path) may be supported by a liquid enclosed in a thick-walled container so that the compressibility of the liquid provides elastic properties of the flow path and pressure or volume pulsation damping can be achieved. The thick-walled container may contain a solid and a damping liquid filler so that the combined total thermal expansion coefficient of the solid (e.g., ceramic) and the damping liquid is equal to the thermal expansion coefficient of the thick-walled container, so that the membrane position and the volume of the high-pressure flow path remain substantially unchanged over a wide temperature range, for example, from 4°C to 60°C. Damper embodiments may also include flow-through elastic structures, such as Bourdon tubes or the like, metal or ceramic microfluidic structures, and the like. A number of different damping devices are established in the field of liquid chromatography and can be implemented in a simple and reliable manner.

[0053] In an embodiment, the control unit is configured to activate the switching of the damping device into the high-pressure path and thus realize its damping operation. For example, a passive damper can be included in the flow path to damp flow pulsations during one of the drives is occupied to perform a metering task, or to help pre-compression of the sample. In addition, the control unit can activate (via one or more switching valves) a switching state, characterized in that: the second fluid drive unit is connected to the high-pressure fluid path (coupled operating mode), and during the damping operation in its high-pressure fluid path, the previously pressurized damper is connected to the sample holding chamber containing the sample, while the fluid path section including the damper and the sample holding chamber is completely fluid blocked. In this way, the damper (i.e. the elastic energy included therein) can be used to bring the fluid sample to a level close to the system high pressure.

[0054] In an embodiment, the control unit is configured to couple a damper device in the flow path between the first fluid drive unit and the sample separation device, in particular in the decoupled operation mode. Thus, the damper device can efficiently compensate for the decoupled second fluid drive unit to keep the fluid flow path in a stable state.

[0055] In an embodiment, the damping device comprises an elastic element, in particular a membrane. In an embodiment, the damping device comprises a damping device cavity configured to contain a fluid / liquid. In an embodiment, the elastic element is arranged on top of said cavity (as a cover).

[0056] In an embodiment, the control unit is further configured to pressure-decouple the second fluid drive unit from the first fluid drive unit in a pressure-decoupled operating mode. In an embodiment, the control unit is further configured to i) pressurize the sample holding chamber before coupling the sample holding chamber to the flow path fluid, wherein the pressurization is performed while the first fluid drive unit is in operation, and / or ii) depressurize the sample holding chamber after coupling the sample holding chamber to the flow path fluid, preferably in preparation for subsequent intake of a fluid sample in the sample holding chamber, wherein the depressurization is preferably performed while the first fluid drive unit is in operation. In this way, an efficient sample pre-compression can be achieved in the described sample separation device.

[0057] In an embodiment, the concept of the present disclosure may be to (temporarily) use one of the two pump drivers (e.g. by having an adequate switching unit, such as a valve, between the two pumps) to meter the sample into the sample loop, while the other pump maintains the flow into the system. As a further aspect, a damping unit may be used (and also sufficiently coupled to the switching unit) in order to smooth / continue the flow during the decoupling of one of the pump drivers (for metering).

[0058] In an embodiment, the sample separation device is configured as a fluid chromatography device, more particularly as a high performance liquid chromatography HPLC device.

[0059] In preparative chromatography systems, a liquid as mobile phase is typically provided at a controlled flow rate (e.g. in the range of 1 mL / min to several thousand mL / min, such as in analytical scale preparative LC in the range of 1-5 mL / min and in preparative scale in the range of 4-200 mL / min) and a pressure in the range of tens to hundreds of bars (e.g., 20-600 bars).

[0060] In high performance liquid chromatography (HPLC), the liquid as the mobile phase usually has to be provided at a very controlled flow rate (e.g., in the range of a few microliters to a few milliliters per minute) and at high pressure (typically 20-100 MPa, 200-1000 bar, currently up to 200 MPa, 2000 bar), at which high pressure the compressibility of the liquid becomes significant.

[0061] In analytical equipment, especially in liquid chromatography (particularly HPLC), it may be important to provide accurate solvent flows even when the specific nature of the solvent is not known or downloaded to the control unit of the analytical equipment.

[0062] The embodiments may be implemented in conventionally available HPLC systems, such as the analytical Agilent 1290 Infinity II LC system or the Agilent 1290 Infinity II Preparative LC / MSD system (both provided by the applicant, Agilent Technologies - see www.agilent.com - which are hereby incorporated by reference).

[0063] One embodiment of the sample separation device includes a pump having a pump piston for reciprocating in a pump working chamber to compress a liquid in the pump working chamber to a high pressure at which the compressibility of the liquid becomes apparent. The pump or the control unit may be configured to process a numerical value of a solvent property (the value is provided to the pump by input by an operator, notification from another module of the instrument, or the like, or the pump derives the solvent property before or during its operation).

[0064] The sample separation unit of the sample separation device preferably comprises a chromatographic column (e.g., see http: / / en.wikipedia.org / wiki / Column_chromatography), which comprises a stationary phase. The column can be a glass or metal tube (e.g., a diameter of 50 μm to 5 mm and a length of 1 cm to 1 m) or a microfluidic column (as disclosed in the Agilent 1200 series HPLC-Chip / MS system provided by EP 1577012 A1 or the applicant Agilent Technologies). Each component is differently retained by the stationary phase and at least partially separated from each other, while they and the eluent propagate through the column at different speeds. At the end of the column, they elute one at a time or at least not completely at the same time. During the entire chromatographic analysis process, the eluent can also be collected in a series of fractions. The stationary phase or adsorbent in column chromatography is generally a solid material. The most commonly used stationary phase for column chromatography is silica gel, surface-modified silica gel, followed by aluminum oxide. Cellulose powder was often used in the past. The most common chromatography modes are ion exchange chromatography, reversed phase chromatography (RP), affinity chromatography or expanded bed adsorption (EBA). The stationary phase is usually a fine powder or gel, and / or microporous for greater surface area.

[0065] Mobile phase (eluent) can be a mixture of pure solvent or different solvents (such as water and organic solvents such as ACN, acetonitrile, etc.). It can be selected to, for example, adjust the retention rate of the complex of concern and / or the amount of mobile phase of the running chromatography. Mobile phase can also be selected so that different complexes or fractions of the fluid sample can be efficiently separated. Mobile phase can include organic solvents that are often diluted with water, such as methanol or acetonitrile. For gradient operation, water and organic matter are delivered in a separate container, and a gradient pump delivers the planned admixture from the container to the system. Other commonly used solvents can be isopropanol, THF, hexane, ethanol and / or any combination thereof, or any combination of these and the aforementioned solvents.

[0066] The fluid sample analyzed by the sample separation device according to the exemplary embodiment of the present disclosure may include, but is not limited to, any type of process liquid, natural samples like juice, body fluids like plasma, or it may be the result of a reaction like from a fermentation broth.

[0067] The pressure in the mobile phase generated by the fluid drive may range from 2-200 MPa (20 to 2000 bar), particularly from 10-150 MPa (150 to 1500 bar), and more particularly from 50-120 MPa (500 to 1200 bar).

[0068] The sample separation device, such as an HPLC system, may further include a detector for detecting separated compounds of the fluid sample, a fractionation unit for outputting separated compounds of the fluid sample, or any combination thereof. For example, a fluorescence detector may be implemented.

[0069] Embodiments of the present disclosure may be implemented or supported in part or in full by one or more suitable software programs, which may be stored on or provided by any type of data carrier and may be executed on or by any suitable data processing unit. The software programs or routines may preferably be applied in or by a control unit.

[0070] By referring to the following more detailed description of the embodiments in conjunction with the accompanying drawings, other objects and many attendant advantages of the embodiments of the present disclosure will be easily appreciated and better understood. Features that are substantially or functionally equivalent or similar will be referred to by the same reference numerals. BRIEF DESCRIPTION OF THE DRAWINGS

[0071] Figure 1 A liquid sample separation device according to an embodiment of the present disclosure is shown, which is particularly used in high performance liquid chromatography (HPLC).

[0072] Figure 2 A sample separation device is shown in a coupled mode of operation according to an embodiment of the present disclosure.

[0073] Figure 3 A sample separation device according to an embodiment of the present disclosure is shown in a first transition state.

[0074] Figure 4 A sample separation device is shown in a decoupled mode of operation according to an embodiment of the present disclosure.

[0075] Figure 5 The fluid paths of a sample separation device are shown in a coupled mode of operation according to an embodiment of the present disclosure.

[0076] Figure 6 A sample separation device fluid path is shown in a first transition state according to an embodiment of the present disclosure.

[0077] Figure 7 The sample separation device fluid paths are shown in a decoupled mode of operation according to an embodiment of the present disclosure.

[0078] Figure 8 A fluid drive device is shown in a coupled mode of operation according to an embodiment of the present disclosure.

[0079] Fig. 9 A fluid drive device is shown in a decoupled mode of operation according to an embodiment of the present disclosure.

[0080] Fig.10 A damping device according to an embodiment of the present disclosure is shown.

[0081] Fig.11 The fluid paths of a sample separation device in a coupled operation mode are shown according to an embodiment of the present disclosure, wherein each fluid drive unit comprises a pump unit.

[0082] Fig.12 The fluid paths of a sample separation device in a decoupled operating mode are shown according to an embodiment of the present disclosure, wherein each fluid drive unit comprises a pump unit.

[0083] Fig.13 The fluid paths of a sample separation device in a coupled operation mode are shown according to an embodiment of the present disclosure, wherein one fluid drive unit includes two pump units.

[0084] Fig.14 The fluid paths of a sample separation device in a decoupled operating mode are shown according to an embodiment of the present disclosure, wherein one fluid drive unit includes two pump units. DETAILED DESCRIPTION

[0085] The drawings are schematic.

[0086] Figure 1A general schematic diagram of a liquid separation system as an example of a sample separation device 10 according to an exemplary embodiment of the present disclosure is depicted. A pump as a fluid drive 20 typically receives a mobile phase from a solvent supplier 25 via a degasser 27, which degases and thereby reduces the amount of gas dissolved in the mobile phase. The mobile phase driver or fluid drive 20 drives the mobile phase through a sample separation unit 30 (such as a chromatographic column) including a stationary phase. A sampler or injector 40 including a fluid valve 112 can be arranged between the fluid drive 20 and the separation unit 30 to apply or add (commonly referred to as sample introduction) a sample fluid to the mobile phase. The stationary phase of the separation unit 30 is configured to separate a complex of a sample liquid. A detector 50 is provided for detecting the complex of the separated sample fluid. A fractionation unit 60 can be provided for outputting the complex of the separated sample fluid.

[0087] Although the mobile phase may include only one solvent, it may also be a mixture of multiple solvents. The corresponding mixing process may be a low-pressure mixing and is arranged upstream of the fluid drive 20, so that the fluid drive 20 has received and pumped the mixed solvent as the mobile phase. Alternatively, the fluid drive 20 may include a plurality of separate pumping units or fluid drive units that each receive and pump different solvents or mixtures, so that the mixing of the mobile phase (received by the separation unit 30) occurs on the high-pressure side and downstream of the fluid drive 20 (or as part thereof). The components (mixture) of the mobile phase may remain constant over time (so-called isocratic mode), or may vary over time (so-called gradient mode).

[0088] The data processing unit or control unit 70 (which may be a PC or workstation, alternatively it may also be a dedicated controller as a handheld controller, or a processing unit, such as a microcontroller, a microprocessor or a plurality of processing units operating in a coordinated manner or at least interacting with each other, included in or as part of one or more system modules 25, 27, 20, 30, 50, 60) may be coupled (as indicated by the dashed arrow) to one or more devices in the sample separation device 10 in order to receive information and / or control operations. For example, the control unit 70 may control the operation of the fluid drive device 20 (e.g. setting control parameters) and receive information about the actual working state (e.g. output pressure at the outlet of the pump 20, etc.) from it. The control unit 70 may also control the operation of the solvent supply 25 (e.g. setting the solvent or solvent mixture to be supplied) and / or the operation of the degasser 27 (e.g. setting control parameters, such as the vacuum degree, etc.), and may receive information about the actual working conditions (e.g. the solvent composition supplied over time, the vacuum degree, etc.) from it. The control unit 70 can further control the operation of the sampling unit or injector 40 (e.g., control sample injection or synchronization of sample injection with the operating state of the fluid drive device 20). The separation unit 30 can also be controlled by the control unit 70 (e.g., select a specific flow path or column, set the operating temperature, etc.), and in turn send information (e.g., operating status) to the control device 70. Correspondingly, the detector 50 can be controlled by the control unit 70 (e.g., regarding spectrum or wavelength settings, setting time constants, starting / stopping data acquisition), and send information (e.g., regarding the detected sample complexes) to the control unit 70. The control unit 70 can also control the operation of the fractionation unit 60 (e.g., in conjunction with data received from the detector 50) and the fractionation unit 60 provides data back to the control unit 70.

[0089] As mentioned above, according to Figure 1 The sample separation device 10 for separating fluid samples includes a fluid drive device 20, which is, for example, presented as a pump, including two fluid drive units 102, 104 (each configured as a high-pressure pump) to drive the mobile phase along a flow path 108 to a sample separation unit 30 presented as a chromatographic separation column. The sample holding chamber 106 is presented as a sample loop here, and is configured to temporarily hold the fluid sample before injection. Therefore, the sample holding chamber 106 is configured to be able to selectively couple with the flow path 108 fluids (to perform sample injection) or decouple with the flow path 108 fluids (to perform sample intake). The sample holding chamber 106 can also be represented as a sample introduction unit, and can be, for example, a sample loop, an injection valve, an automatic sampler, etc. The sample holding chamber 106 is responsible for filling the fluid sample into the flow path 108.

[0090] The control unit 70 may be a processor and may be configured to control the entire operation of the sample separation device 10, and the control unit 70 may be configured to pressure-decouple a corresponding one of the fluid drive units 102, 104 from the flow path 108 in one operation mode of the sample separation device 10, so that at least one pressure-decoupled fluid drive unit 102, 104 can pressurize the sample receiving chamber 106 before fluidly coupling the sample receiving chamber 106 with the flow path 108. The fluid drive units 102, 104 of the fluid drive device 20 are two functionally cooperating fluid pumps that drive the mobile phase before injecting the fluid sample from the sample receiving chamber 106 into the flow path 108.

[0091] The corresponding one of the fluid drive units 102, 104 that is currently pressure-decoupled from the flow path 108 can be configured to, in addition to taking in a sample from a sample bottle, also raise the sample holding chamber 106 from ambient pressure to the system pressure (e.g., 1200 bar) in the flow path 108 before switching or otherwise connecting the sample holding chamber 106 to the flow path 108. The control unit 70 can control the fluid coupling of the sample holding chamber 106 to the flow path 108 after pressurization by correspondingly switching the fluid valve 112. In addition, the control unit 70 is suitable for operating the corresponding remaining (i.e., not pressure-decoupled or pressure-separated) fluid drive units 102, 104 to continuously supply the mobile phase to the sample separation unit 30 while the currently decoupled fluid drive unit 102, 104 is decoupled from the flow path 108. In addition, the fluid path of the instrument can be switched by the control unit 70 through a fluid valve (not shown) or another switching device to selectively switch a corresponding one of the fluid drive units 102, 104 to be fluidically coupled or pressure-coupled with the flow path 108, or to be pressure-decoupled from the flow path 08.

[0092] Figure 1 It is also schematically shown how to fill the sample holding chamber 106 with a fluid sample. For example, the needle 91 can be temporarily withdrawn from the needle holder (not shown) of the injector 40 and can be temporarily immersed (see reference numeral 95) in the fluid sample liquid 92 in the bottle or other fluid container 93. Then, a sample of the fluid sample liquid 92 can be drawn into the sample holding chamber 106 via the needle 91. The fluid sample in the sample holding chamber 106 is then at or near ambient pressure.

[0093] Figure 2 FIG. 1 shows a sample separation device 10 in a coupled operation mode (main pass) according to an embodiment of the present disclosure (eg, as for example for Figure 1In the coupled operation mode, the valve 112 is switched so that the first fluid drive unit 102 and the second fluid drive unit 104 are coupled in series, whereby the first fluid drive unit 102 is arranged upstream of the second fluid drive unit 104 in the process direction. Therefore, the first fluid drive unit 102 is fluidically connected to the mobile phase reservoir 25 and pumps / extracts the mobile phase (one or more solvents) toward the second fluid drive unit 104 in the process direction.

[0094] The second fluid drive unit 104 pumps the mobile phase via the sample holding chamber 106 toward the separation unit 30 along the process direction of the flow path 108. Therefore, in the coupled operation mode, the mobile phase flows through the sample holding unit 106 downstream of the fluid drive device 20 along the process direction, thereby taking up the fluid sample contained in the sample holding unit 106, and the mobile phase is transported to the sample separation unit 30 together with the fluid sample. In the coupled operation mode, the first fluid drive unit 102 and the second fluid drive unit 104 are pressure-coupled to each other, and both are in the high-pressure path. In this coupled operation mode, the damping device 160 is not switched into the flow path 108.

[0095] Figure 3 The sample separation device 10 in a first transition state according to an embodiment of the present disclosure is shown. When switching between the coupled operating mode and the decoupled operating mode, the first transition state (regulation) temporarily exists. It can be seen that the sample holding chamber 106 is cut out from the flow path 108 (from the fluid drive device 20 to the sample separation unit 30). Therefore, the fluid drive device 20 is now directly connected to the sample separation unit 30 via the flow path 108 (without the fluid sample in the mobile phase).

[0096] In this (optional) regulation configuration, the sample is "parked" in the sample holding chamber 106 (needle) and the primary and secondary pistons 102, 104 are flushing the flow path 108 and column 30 to compensate for potential artifacts that may result from operating the pump 20 in a single piston 102 configuration.

[0097] In certain embodiments (including different switching valve designs, not shown), the damping device 160 can be preloaded to the system pressure or even higher, for example by being briefly fluidly isolated from one of the pump drivers 102, 104, which then loads the damping device 160 to the high pressure at the appropriate time, and in the next transient switching position, the sample loop can be connected to the damping device 160 and thus pressure balanced to a pressure close to the system pressure, while the fluid driver 102, 204 can provide flow into the system. This can be similar to Figure 3 After the sample has been pressure balanced in this way, the sample loop can be switched to the main flow.

[0098] Figure 4 A sample separation device 10 in a decoupling operation mode (bypass) according to an embodiment of the present disclosure is shown. From the above-mentioned first transition state, the switching valve 112 is switched to the decoupling operation mode at this time. Therefore, the first fluid drive unit 102 and the second fluid drive unit 104 (series fluid coupling in the coupled operation mode) are decoupled from each other at this time (no fluid flow between these entities). On the contrary, the first fluid drive unit 102 is coupled to the sample separation unit 30 at this time, and the second fluid drive unit 104 and / or the sample holding chamber 106 are not between the two in the flow path 108. The first fluid drive unit 102 can extract / pump the mobile phase from the mobile phase container 25 toward the sample separation unit 30 at this time, but cannot inject the sample under this configuration.

[0099] The damping device 160 is thus switched in the flow path 108 between the first fluid drive unit 102 and the sample separation unit 30 in order to damp the flow pulsations (see also Fig.10 ). The damping device 160 can efficiently compensate for the decoupled second fluid drive unit 104.

[0100] The decoupled second fluid drive unit 104 is now coupled to the sample holding chamber 106 fluid in the low-pressure decoupled flow path 109. Since both the second fluid drive unit 104 and the sample holding chamber 106 are decoupled from the flow path 108, sample intake (e.g., from a sample bottle) can be performed. The second fluid drive unit 104 thus operates as a metering device that draws a specific amount of sample into the sample holding chamber 106. Most interestingly, no additional metering device (as in conventional systems) is required to meter / intake the sample into the sample holding chamber 106.

[0101] In the decoupled operation mode, the first fluid drive unit 102 and the second fluid drive unit 104 are pressure-decoupled from each other. In a specific embodiment, the sample flow path 109 from the second fluid drive unit 104 through the sample holding unit 106 can be blocked downstream of the sample holding unit 106 in the process direction. When the sample flow path 109 is blocked and the second fluid drive unit 104 provides pressure (by pumping) on ​​the sample holding chamber 106, the fluid sample can be (pre) compressed. The pre-compressed sample can be more efficiently injected into the high-pressure path.

[0102] More specifically, once the sample is pre-compressed, the valve can be switched to Figure 3Obviously, during this switching, the flow path 109 is never opened, so the high pressure is maintained in the flow path 109, that is, the pre-compressed sample state is maintained. Likewise, after the (optional) adjustment period, during the process of switching the valve back to the coupled state, the pre-compressed sample in the containing unit 106 in the flow path 109 is never decompressed, but is connected to the high pressure path or its component that stays at high pressure (system pressure).

[0103] In other words, in one variation of the system, the metering device is eliminated and the secondary piston 104 of the pump 20 is used to meter the fluid sample while the primary piston 102 continues to provide flow in the analysis path 108 of the system (in a bypass configuration). The pump 20 then effectively operates as a single piston pump 102. To increase the life of the fluid components of the flow path including the column 30, a passive damper 160 may be used to reduce pressure spikes. In the bypass configuration, the secondary piston 104 is used as a metering unit to meter the sample and run the injection subpath, such as pre-compressing the sample, etc.

[0104] Figure 5 FIG. 2 shows the fluid path of the sample separation device 10 in the coupled operation mode (main pass) according to an embodiment of the present disclosure. Figure 2 The mode described in FIG. 1 is very similar, but is explained in another way. The first fluid driving unit 102 pumps the first solvent A into the flow path 108, and the second fluid driving unit 104 pumps the second solvent B into the flow path 108. At the mixing point 116, the two solvents A and B are mixed to flow as a mobile phase along the flow path 108 toward the sample separation unit 30. In this example, the switching unit 112 couples the sample holding chamber 106 to the flow path 108 so that the held sample is injected into the mobile phase.

[0105] The present invention is applicable to a binary pump (a pump comprising at least two pump channels for pumping respective fluids, and the desired fluid composition can be generated in a mixing unit downstream of the pump drive, thereby generating a high-pressure flow path). Any channel of the binary pump or the drive included in any pump channel can be used as the first drive unit 102 and / or the second drive unit 104. One channel of the binary pump can remain unchanged, while the other channel can be adjusted (compare Fig.13 and Fig.14 ).

[0106] Figure 6 FIG. 2 shows the fluid path of the sample separation device 10 in a first transition state according to an embodiment of the present disclosure. Figure 3 ), the sample holding chamber 106 is decoupled from the flow path 108.

[0107] Figure 7 FIG. 1 shows the fluid path of the sample separation device 10 in a decoupled operating mode (bypass) according to an embodiment of the present disclosure. This operating mode is similar to Figure 4 The mode described in is very similar, but is illustrated in another way. The first fluid drive unit 102 is fluidically coupled to the sample separation unit 30 via the (high pressure) flow path 108. The second fluid drive unit 104 is still coupled to the mixing point 116 and the sample holding chamber 106, but is decoupled from the first fluid drive unit 102 and the flow path 108. Therefore, the path 109 from the second fluid drive unit 104 to the sample holding chamber 106 is at normal pressure, and the second fluid drive unit 104 can control the intake of the sample into the sample holding chamber 104.

[0108] Figure 8 A detailed view of a fluid drive device 20 in a coupled operation mode according to an embodiment of the present disclosure is shown. The fluid drive device 20 includes a first fluid drive unit 102 having a first piston 121 and a second fluid drive unit 104 having a second piston 122. When the first fluid drive unit 102 is connected to the mobile phase / solvent container 25, the second fluid drive unit 104 is coupled / can be coupled to the sample holding chamber 106 and / or the sample separation unit 30. Upstream in the process direction of the first fluid drive unit 102, a first check valve 123 is arranged, and upstream in the process direction of the second fluid drive unit 104, a second check valve 124 is arranged. In this coupled operation mode, the first fluid drive unit 102 and the second fluid drive unit 104 are connected in series (fluidly) via a switching valve 112.

[0109] Fig. 9 Detailed view of the fluid drive device 20 in the decoupled operation mode according to an embodiment of the present disclosure is shown. In the bypass mode, the switching unit 112 decouples the first fluid drive unit 102 from the second fluid drive unit 104. The first fluid drive unit 102 is now coupled to the sample separation unit 30 through the switching valve 112, while the second fluid drive unit 104 is now coupled to the sample holding chamber 106 through the switching valve 112.

[0110] Fig.10 A damping device 160 according to an embodiment of the present disclosure is shown. The damping device 160 can be a passive damping device, particularly for damping flow pulsations in the flow path 108 when the second fluid drive unit 104 is decoupled. The damping device 160 can assist in a fluid sample intake operation and / or a fluid sample compression operation. For example, the control unit 70 is configured to couple the damping device 160 in the flow path 108 between the first fluid drive unit 102 and the sample separation device 30 in the decoupled operation mode.

[0111] The exemplary damping device 160 shown includes an elastic element 165, such as a membrane on top of a damping device cavity 161. Schematically shown, cavity 161 is surrounded by very thick side walls to be robust to the high pressures in HPLC. Cavity 161 is configured to contain a liquid 162 below the elastic element 165.

[0112] The figure shows that the damping device 160 can effectively damp flow pulsations (pressure spikes) compared to a system without the damping device 160.

[0113] Fig.11 The fluid paths of a sample separation device in a coupled operation mode according to an embodiment of the present disclosure are shown, wherein each fluid drive unit 102 , 104 comprises one pump unit 121 , 122 . Fig.11 An example comparable to Figure 2 . Here, the fluid drive device 20 includes a first fluid drive unit 102 and a second fluid drive unit 104. It can be seen that the first fluid drive unit 102 is a single piston pump, which includes a pump unit 121, i.e., a piston in a piston cylinder. In order to drive the first pump unit 121, the first fluid drive unit 102 includes a first motion source 125, which is a motor here. In the same way, the second fluid drive unit 104 is also a single pump, which includes a pump unit 122, i.e., a piston in a piston cylinder. In order to drive the second pump unit 122, the second fluid drive unit 104 includes a second motion source 126, which is another motor here. Therefore, the first pump unit 125 and the second pump unit 126 are mechanically decoupled and can therefore move independently of each other.

[0114] Fig.12 The fluid paths of a sample separation device in a decoupled operating mode are shown according to an embodiment of the present disclosure, wherein each fluid drive unit 102 , 104 comprises one pump unit 121 , 122 . Fig.12 An example comparable to Figure 4 The configuration of the fluid drive units 102 and 104 is as described above for Fig.11 described.

[0115] Fig.13 A sample separation device fluid path is shown in a coupled operation mode according to an embodiment of the present disclosure, wherein the first fluid drive unit 102 comprises two coupled pump units 121a, 121b. Fig.13 It means Figure 2 and Fig.11 The main pass configuration described above. Fig.11The difference is that the first fluid drive unit 102 includes two pump units 121a, 121b (double piston pumps) instead of only one pump unit (single piston pump). It can be seen that each pump unit 121a, 121b includes a piston / cylinder pair, and the two pump units 121a, 121b are coupled in series with each other. Therefore, the first fluid drive unit 102 includes only one motion source 125 (here is a motor) that drives both pump units 121a, 121b. Therefore, pump units 121a, 121b are mechanically coupled and cannot move independently of each other. In contrast, the second fluid drive unit 104 includes only one pump unit 122 with its own motion source 126.

[0116] It should also be noted that Fig.11 and Fig.12 Compared to the example of , no damping device 160 is applied. The use of a dual piston pump can stabilize the flow, thereby making the damping device 160 redundant.

[0117] Fig.14 The sample separation device fluid path is shown in a decoupled operation mode according to an embodiment of the present disclosure, wherein one fluid drive unit 102 includes two pump units 121a, 121b. Fig.14 An example comparable to Figure 4 and Fig.12 However, the configuration of the fluid drive units 102, 104 is as described above for Fig.13 described.

[0118] It should be noted here that Figures 11 to 14 represents a simple embodiment of the present invention having basic functions, while Figures 2 to 4 Possible enhanced embodiments are shown, which include advanced functional features such as sample pre-compression, decoupling of sample loops containing compressed samples, column pre-conditioning before injection, etc. In summary, Figure 2-Figure 4 and Figure 11-Figure 14 Only exemplary embodiment variations of the present disclosure are represented, and other switching valve configurations and geometries as well as different pump topologies as well as the “binary”, “quaternary”, series-driven, parallel-driven topologies described in more detail above are possible.

[0119] It should be noted that the term "comprising" does not exclude other elements, and "a" or "an" does not exclude a plurality. Elements described with respect to different embodiments may also be combined. It should also be noted that the reference signs in the claims should not be interpreted as limiting the scope of the claims.

[0120] Reference numerals list

[0121] 10 Separation equipment

[0122] 20 Fluid drive device

[0123] 25 Solvent supply

[0124] 27 Degasser

[0125] 30 Sample separation device, unit

[0126] 40 Sample Injector

[0127] 50 Detector

[0128] 60 Fractionation Unit

[0129] 70 Data processing device, control unit

[0130] 91 needles

[0131] 92 samples

[0132] 93 Sample Container

[0133] 95 Sample intake

[0134] 102 First fluid drive unit

[0135] 104 Second fluid driving unit

[0136] 106 Sample holding chamber, loop

[0137] 108 Flow Path

[0138] 109 Sample flow path, decoupled

[0139] 112 Switching unit, fluid valve

[0140] 116 Mixing Points

[0141] 121 first piston, first pump unit

[0142] 121a First pump unit

[0143] 121b Second pump unit

[0144] 122 second piston, second pump unit

[0145] 123 First check valve

[0146] 124 Second check valve

[0147] 125 First Motor, Public Motor

[0148] 126 Second Motor

[0149] 160 Damping device

[0150] 161 Damping chamber

[0151] 162 Fluid Filler

[0152] 165 Elastic elements, membranes

[0153] P process direction

Claims

1. A sample separation device (10) for separating a fluid sample, the sample separation device (10) comprising: A fluid driving device (20) comprising a first fluid driving unit (102) and a second fluid driving unit (104) for driving a mobile phase along a flow path (108) to a sample separation unit (30); a sample holding chamber (106), configured to hold the fluid sample; and a control unit (70) configured to control the respective operations of the fluid drive units (102, 104) and to control the fluid decoupling of the second fluid drive unit (104) from the flow path (108) in a decoupling operation mode of the sample separation device (10), Wherein, the control unit (70) is further configured to control the decoupled second fluid drive unit (104) in the decoupled operation mode to fluidly coupled to the sample holding chamber (106), and The sample is taken into the sample receiving chamber (106).

2. The sample separation device (10) according to claim 1, in, In the decoupled operation mode, the first fluid drive unit (102) is coupled to the separation unit (30), and / or Wherein, in the decoupling operation mode, the second fluid driving unit (104) is decoupled from the separation unit (30).

3. The sample separation device (10) according to claim 1 or 2, in, In the decoupled operating mode, the second fluid drive unit (104) operates as a metering device, in particular a metering pump, to take the fluid sample from the sample container (93).

4. The sample separation device (10) according to any one of claims 1 to 3, in, The control unit (70) is further configured to at least partially block the sample flow path (109) from the second fluid drive unit (104) through the sample holding unit (106) in the decoupled operating mode, in particular in the process direction (P) downstream of the sample holding unit (106), so as to in particular compress the fluid sample.

5. The sample separation device (10) according to any one of the preceding claims, comprising: in, The control unit (70) is further configured to control the coupling between the first fluid drive unit (102) and the second fluid drive unit (104) in a coupled operation mode, wherein the first fluid drive unit (102) and the second fluid drive unit (104) are fluidically coupled to each other in series or in parallel.

6. The sample separation device (10) according to claim 5, in, In the coupled operation mode, the first fluid drive unit (102) and the second fluid drive unit (104) are pressure-coupled to each other; and / or Wherein, in the decoupling operation mode, the first fluid drive unit (102) and the second fluid drive unit (104) are pressure-decoupled from each other, In particular, the first fluid drive unit (102) is coupled in a high-pressure path (108), and / or the second fluid drive unit (104) is coupled in a normal-pressure path (109).

7. The sample separation device (10) according to claim 5 or 6, in, In the coupled operation mode, the mobile phase, in particular the solvent, is pumped out by the first fluid driving unit (102), in particular from the solvent container (25), and then flows to the second fluid driving unit (104).

8. The sample separation device (10) according to any one of claims 5 to 7, in, In the coupled operating mode, the mobile phase flows through the sample holding unit (106) downstream of the fluid driving device (20) in a process direction (P), thereby picking up the fluid sample held in the sample holding unit (106).

9. The sample separation device (10) according to any one of the preceding claims, in, The sample holding unit (106) is configured as one of a sample loop, a multi-sample storage, a sampler, an automatic sampler, and an injection needle; and / or The sample holding chamber (106) is configured to be selectively coupled to or decoupled from the flow path (108) fluid.

10. The sample separation device (10) according to any one of the preceding claims, in, The first fluid drive unit (102) and / or the second fluid drive unit (104) comprises two or more pump units (121a, 121b) connected to a common motion source (125), in particular a motor, and / or wherein the two or more pump units (121a, 121b) are mechanically dependent on each other; and / or wherein the first fluid drive unit (102) is arranged upstream of the second fluid drive unit (104) along the process direction (P); and / or Wherein, the first fluid driving unit (102) and the second fluid driving unit (104) are fluidically coupled to each other in series or in parallel.

11. The sample separation device (10) according to any one of the preceding claims, further comprising: A switching unit (112), in particular a fluid valve, is arranged between the first fluid drive unit (102) and the second fluid drive unit (104) along a process direction (P) and is coupled to the control unit (70), wherein the control unit (70) is configured to switch between the coupled operating mode and the decoupled operating mode via the switching unit (112).

12. The sample separation device (10) according to any one of the preceding claims, in, The sample separation device (10) has no metering device, in particular a metering pump.

13. The sample separation device (10) according to any one of the preceding claims, further comprising: A damping device (160), in particular a passive damping device, is provided for damping flow pulsations in the flow path (108).

14. The sample separation device (10) according to claim 13, in, The control unit (70) is configured to trigger a damping operation of the damping device (160) to assist a fluid sample intake operation and / or a fluid sample compression operation.

15. The sample separation device (10) according to claim 13 or 14, in, The control unit (70) is configured to couple the damping device (160) in the flow path (108) between the first fluid drive unit (102) and the sample separation unit (30), in particular in the decoupled operation mode.

16. The sample separation device (10) according to any one of claims 13 to 15, in, The damping device (160) comprises an elastic element (165), in particular a membrane; and / or Therein, the damping device (160) comprises a damping device chamber (161) which is configured to receive a liquid (162), in particular below the elastic element (165).

17. The sample separation device (10) according to any one of the preceding claims, wherein The control unit (70) is further configured as follows: Before coupling the sample holding chamber (106) to the flow path (108) fluidically, pressurizing the sample holding chamber (106), wherein the pressurization is performed while the first fluid drive unit (102) is in operation; After the sample holding chamber (106) is fluidically coupled to the flow path (108), the sample holding chamber (106) is depressurized, preferably in preparation for subsequent intake of a fluid sample in the sample holding chamber (106), wherein the depressurization is preferably performed while the first fluid drive unit (102) is in operation.

18. The sample separation device (10) according to any one of the preceding claims, The device is configured as a fluid chromatography apparatus, more particularly a high performance liquid chromatography (HPLC) apparatus.

19. A method of operating a sample separation device (10), the method comprising: The mobile phase is driven along a flow path (108) to a sample separation unit (30) by a fluid driving device (20), wherein the fluid driving device comprises a first fluid driving unit (102) and a second fluid driving unit (104); Accommodating a fluid sample in the sample receiving chamber (106); In a decoupled operation mode of the sample separation device (10), the second fluid drive unit (104) is fluidically decoupled from the flow path (108); In the decoupled operation mode, fluidically coupling the decoupled second fluid drive unit (104) to the sample holding chamber (106); and The sample is taken into the sample receiving chamber (106).

20. Use of a fluid drive unit (104) of a fluid drive device (20) of a chromatographic apparatus (10), wherein the fluid drive unit (104) decoupled from a separation flow path (108) serves as a metering device to trigger the intake of a fluid sample into a sample holding chamber (106).

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