Degasser with protected sensor line for an analytical device

Abstract

A degasser 100 comprising a fluid line 150, a first 120 and second 130 degasser chamber coupled to the fluid line at a first 121 and second 131 coupling point, a suction device 110 coupled to the flui

Description

FIELD OF THE DISCLOSURE

[0001] The present disclosure relates to a degasser for an analytical device, comprising a fluid line, a first degasser chamber coupled to the fluid line at a first coupling point, a second degasser chamber coupled to the fluid line at a second coupling point, a suction device coupled to the fluid line to suck fluid from the first degasser chamber and the second degasser chamber, a sensor line coupled to the fluid line, a sensor device and a gas supply, both coupled to said sensor line. Further, the present disclosure refers to an analytical device, in particular a chromatography device such as a high performance liquid chromatography (HPLC) device, that comprises said degasser, and to a method of operating a degasser. BACKGROUND ART

[0002] Analytical devices are provided for analysing a sample, such as for carrying out a chromatographic separation of the sample.

[0003] For example, for liquid separation in a chromatography system, a mobile phase comprising a sample fluid (e.g. a chemical or biological mixture) with compounds to be separated is driven through a stationary phase (such as a chromatographic column packing), thus separating different compounds of the sample fluid which may then be identified.

[0004] The mobile phase, typically comprised of one or more solvents, is pumped under high-pressure typically through a chromatographic column containing packing medium (also referred to as packing material or stationary phase). As the sample is carried through the column by the liquid flow, the different compounds, each one having a different affinity to the packing medium, move through the column at different speeds. Those compounds having greater affinity for the stationary phase move more slowly through the column than those having less affinity, and this speed differential results in the compounds being separated from one another as they pass through the column. The stationary phase is subject to a mechanical force generated in particular by a hydraulic pump that pumps the mobile phase usually from an upstream - 1 - connection of the column to a downstream connection of the column. As a result of flow, depending on the physical properties of the stationary phase and the mobile phase, a relatively high-pressure drop is generated across the column.

[0005] The mobile phase with the separated compounds exits the column and passes through a flow cell of a detector. The separated fluidic sample flows through the flow cell and is illuminated by light from a light source while being optically detected by the detector. The detector registers and / or identifies the molecules, for example by spectrophotometric absorbance measurements or fluorescence measurements. A two-dimensional plot of the detector measurements against elution time or volume, known as a chromatogram, may be made, and from the chromatogram the compounds may be identified and quantified. For each compound, the chromatogram displays a separate curve feature also designated as a "peak".

[0006] Such an HPLC system frequently includes a degasser which at least partially removes gas bubbles from the mobile phase and / or gases which are dissolved therein before reaching the fluid drive. Gas bubbles disturb the regular flow of the eluant (since sucking a liquid with gas bubbles may lead to sucking erroneous liquid amounts), may cause wrong solvent compositions, and lead to a noise in the detector and to further chromatographic artifacts.

[0007] Degassers are further used for removing gaseous components from solvents in order to avoid pressure ripples when pressurizing said solvents (as the mobile phase). Typically, the solvents are conducted by a tube (having a permeable membrane) through a vacuum chamber, which causes gases, dissolved in the solvents, to outgas into the vacuum chamber.

[0008] Figure 4 illustrates a conventional degasser 200. Different mobile phases are streamed through respective degasser chambers 220, 230. All of these degasser chambers 220,230 are coupled respectively with a common fluid line 250. At a central coupling point 251, the gases from the degassed fluids from the degassing chambers are collected and streamed all together towards a vacuum pump 210. The vacuum pump 210 hereby drives the flow of the (degassed) gases. A pressure sensor 260 is coupled 261 between the central coupling point 251 and the vacuum pump 210 to control the pressure in the system.

[0009] Figure 5 illustrates a further conventional degasser 200, wherein all degassing chambers 220, 230 are directly connected to the central coupling point 251 without an additional common flow line 250.

[0010] However, it is still difficult to efficiently degas a mobile phase in an HPLC system. Specifically, undesired flow between degasser chambers (cross-talk, crossflow, diffusion / infiltration of gases) can be considered a problem. Further, sensors like the pressure sensor or a gas vent can be harmed by the organic solvent gases of the mobile phase. SUMMARY OF THE DISCLOSURE

[0011] There may be a need to degas a mobile phase in an efficient and secure manner. The object is solved by the independent claims. Further embodiments are shown by the dependent claims.

[0012] According to a first aspect of the invention, there is described a degasser (a device configured to degas a fluid such as a mobile phase), in particular for an analytical device (e.g. a HPLC), comprising:

[0013] i) a fluid line (a vacuum line) (e.g. an elongated device suitable to stream a fluid therein).

[0014] ii) a first degasser chamber (e.g. configured to degas a first fluid, in particular a first mobile phase) coupled / connected to the fluid line at a first coupling point.

[0015] iii) a second degasser chamber (e.g. configured to degas a second fluid, in particular a second mobile phase, in particular different from the first mobile phase) coupled / connected to the fluid line at a second coupling point (in particular different from the first coupling point).

[0016] iv) a suction device (in particular a vacuum pump), coupled to the fluid line (in particular at a suction coupling point) to suck fluid (e.g. gas and / or vapor) from the first degasser chamber and the second degasser chamber (along the fluid line in a (main) fluid (vapor) streaming (towards the suction device) direction downstream).

[0017] v) a sensor line (in particular a part of the fluid line) coupled to the fluid line - 3 - (in particular in (main) fluid streaming direction upstream) (e.g. at the second coupling point).

[0018] vi) a sensor device (e.g. a pressure sensor), coupled to the sensor line (in particular at a sensor coupling point) (in particular in (main) fluid (vapor) streaming direction upstream of the second coupling point).

[0019] vii) a gas supply (e.g. a vent, to supply a gas from exterior to the fluid line / sensor line; e.g. to prevent / avoid / remove condensation) coupled to the sensor line (in particular at a gas coupling point).

[0020] According to a second aspect of the invention, there is described an analytical device (for analyzing a fluidic sample), wherein the analytical device comprises at least one degasser (chamber) as described above. [0021 ] According to a third aspect of the invention, there is described a method for operating a degasser as described above. In particular, the method comprises: i) sucking the fluid (in particular gas / vapor) along the fluid (vacuum (tubing)) line (in main fluid streaming direction) from the first degasser chamber and the second degasser chamber towards the suction device in (main) fluid streaming direction downstream, ii) sensing a parameter, in particular pressure, by the sensor device (in main fluid streaming direction) upstream of the streaming fluid (gases) (of the degasser chambers), and iii) supplying gas by the gas supply (to the main fluid stream and / or streaming fluid).

[0022] In the context of the present document, the term “degasser” in particular denotes a device which is able to specifically perform processing of a mobile phase in such a way that gas constituents which are dissolved in the liquid (in particular gas bubbles, further in particular gas bubbles and / or dissolved gases, in particular air constituents) are fully or partially removed. In an embodiment, the degasser may accomplish the degassing by pervaporation, i.e. a membrane method for purifying liquid mixtures. In the context of a pervaporation, a membrane may be used through which a gas to be removed diffuses much better than the liquid. For example, degassing may also be performed by conducting the liquid through special hoses during degassing (for example, made of a correspondingly configured material, such as Teflon™ AF material) which is more impermeable for the liquid and is more permeable for the gas constituents. Outside the hose, a vacuum, a low-pressure, or at least a reduced partial pressure with respect to the gases which are to be removed from the liquid may be established. Thereby, the gas constituents can leave the liquid at least partially through the hose wall, such that the liquid is at least partially degassed. Alternatively to the described hose membranes in a degasser, it is also possible to provide a planar permeable degassing membrane which accomplishes a separation of a liquid phase from a vacuum region or a low-pressure region. A degassing membrane may be permeable for gas including vapor.

[0023] In the context of the present document, the term “suction device” in particular denotes a unit which sucks the gas which is removed from a mobile phase from the degasser chambers, such as from a space of the degasser chamber which is facing away from the degassing membrane. For example, such a suction device may be configured as a vacuum pump, to which the at least one fluid line / conduit may be connected. Also, a vapor comprising solvent molecules of the mobile phase (evaporated solvent) from the mobile phase which may undesirably passing through the degassing membrane may be partially sucked by the suction device.

[0024] In the context of the present document, the term “gas supply (device)” may in particular denote a unit / device which supplies an associated gas (for example ambient air or another gas, for example nitrogen) to the fluid line and / or the sensor line. In this context, the term gas supply may express that a gas is added to the flow line and the degasser chambers. In an embodiment, the gas supply is a passive element, e.g. a gas inlet or a gas introduction port / device. In another embodiment, the gas supply may be an active element, e.g. an actively controlled gas supply. The supply of gas to the fluid line and the degasser chambers may advantageously suppress a condensation in the degasser chambers and may inhibit an undesired crossflow of gas between the degasser chambers, in particular when multiple degasser chambers are provided. The gas supply may comprise a known volume flow and / or a controlled restriction.

[0025] In the context of the present document, the term “coupling point” may in particular refer to a coupling / connection region between a device (e.g. the suction device, sensor device) and / or a degassing chamber to the fluid line. The fluid line may transport a main fluid stream towards the suction device (sucked by the suction device) and the coupling points may (fluidically) couple the devices to said main fluid stream along the fluid line. For example, each degassing chamber may be coupled to the fluid line at a separate (or similar) coupling point (e.g. a T-junction). Thereby, the suction device may also suck gas from the degassing chambers to the main fluid stream (in the fluid line) and thereby towards the suction device. In an example, the sensor device and / or the gas supply may also be coupled (via the sensor line) to the main fluid stream in the fluid line via the same or respective coupling points, in particular in case the sensor line is configured as a part of the fluid line.

[0026] In the context of the present document, the term “main fluid stream” may in particular refer to a principal fluid stream (from the sensor line; sensor device / gas supply) in direction towards the suction device. The suction device may suck fluid / gas from the fluid line and hence from the degassing chambers. The streams from the degassing chambers may be seen as minor fluid streams that join the main stream along the fluid line towards the suction device. The term “downstream” may hence refer to a proximity to the suction device (“closer to the suction device, in the direction to the suction device”), while the term “upstream” may refer to a distality to the suction device (“away from the suction device, in the direction away from the suction device”). In a preferred example, the sensor device may be coupled to the main fluid stream upstream of the degassing chambers. In a further example, the gas supply may also be coupled to the main fluid stream upstream of the degassing chambers and upstream / downstream of the sensor device.

[0027] In the context of the present document, the term “sensor line” may in particular refer to an elongated device, suitable to stream a fluid therein, that is coupled with the sensor device, e.g. at a sensor coupling point. In an example, the sensor line is a part of the fluid line that is located in the main fluid streaming direction upstream of a main part of the fluid line, to which the degasser chambers are coupled. For example, the sensor line can be arranged at or upstream of the second coupling point (being the degasser chamber coupling point most upstream / distal from the suction device). In another example, the sensor line may be a separate line coupled to the fluid line. In a preferred example, the sensor line is arranged so that the sensor device (is coupled to the main fluid stream and) is protected from the gas (in particular gas of organic solvent; in other words: solvent vapor) of the degassing chambers that streams towards the suction device. In a further preferred example, the gas supply is - 6 - also coupled to the sensor line, thereby also protecting the gas supply from the solvent vapor of the degassing chambers.

[0028] In the context of the present document, the term “analytical device” may in particular refer to a device suitable to perform an analysis of a sample. In an example, the analytical device is applied to analyze (characterize) a sample by sample separation (such as chromatography). In the context of the present document, the term “chromatography device” may in particular refer to an instrument suitable to perform a chromatographic analysis, preferably for analysing a sample, such as for carrying out a chromatographic separation of the sample. Examples of an analytical device may include a liquid chromatography (LC) instrument, in particular a high performance liquid chromatography instrument (HPLC) or a ultra-high performance liquid chromatography instrument (UHPLC), an electrophoresis system, a microfluidic device, a cell sorter (e.g. FACS - Fluorescence Activated Cell Sorting), or a spectrophotometer. In an embodiment, the analytical device comprising an (optical) detection device coupled to or couplable to a source of pressure.

[0029] In the context of this document, the term “fluidic sample” may particularly denote any liquid and / or gaseous medium, optionally including also (dissolved) solid substances, which is to be analyzed. Such a fluidic sample may comprise a plurality of fractions of molecules which shall be separated, for instance small mass molecules or large mass biomolecules such as proteins. Separation of a fluidic sample into fractions may involve a certain separation criterion (such as mass, volume, chemical properties, etc.) according to which a separation is carried out.

[0030] In the context of this document, the term “mobile phase” may particularly denote any liquid and / or gaseous medium which may serve as fluidic carrier of the fluidic sample during separation. A mobile phase may be a solvent or a solvent composition (for instance composed of water and an organic solvent such as ethanol or acetonitrile). In an isocratic separation mode of a liquid chromatography apparatus, the mobile phase may have a constant composition over time. In a gradient mode, however, the composition of the mobile phase may be changed over time, in particular to desorb fractions of the fluidic sample which have previously been adsorbed to a stationary phase of a separation unit.

[0031] In the context of the present document, the term “fluid / solvent drive” (or - 7 - pump device) may particularly denote an entity capable of driving a fluid (i.e. a liquid and / or a gas, optionally comprising solid particles), in particular the fluidic sample and / or the mobile phase. For instance, the fluid drive may be a pump (for instance embodied as piston pump or peristaltic pump) or another source of high pressure. For instance, the fluid drive may be a high-pressure pump, for example capable of driving a fluid with a pressure of at least 500 bar, currently up to 1500 bar.

[0032] In the context of the present document, the term “sample separation unit” may particularly denote a fluidic member through which a fluidic sample is transferred and which is configured so that, upon conducting the fluidic sample through the separation unit, the fluidic sample will be separated into different groups of molecules or particles. An example for a separation unit is a liquid chromatography column which is capable of trapping or retarding and selectively releasing different fractions of the fluidic sample.

[0033] According to an exemplary embodiment, the invention may be based on the idea that a degasser (for an analytical device) may be operated in an efficient and secure manner, when the degassing chambers are coupled at separate coupling points to a common fluid line, wherein a main fluid stream flows towards a suction device, and a sensor device as well as a gas supply are coupled to a sensor line that is coupled to the flow line in main fluid stream direction upstream of the degasser chamber coupling points. In other words, devices such as the sensor device and the gas supply, while still being connected to the main fluid stream of the flow line, are moved to a region that is free (not affected) of the (direct) gasses and solvent vapors originating from the degasser chambers. As a consequence, said devices are protected from harmful / aggressive solvent vapors such as acetonitrile or methanol gases.

[0034] The described architecture may combine a plurality of advantages. In the first place, solvents used for the mobile phase are often harmful or destructive for sensitive devices like a sensor device. Also, the gas supply may be damaged by gas flow from the degasser chambers. By placing these sensitive devices in a region that is free of the gas flow from the degasser chambers (at the sensor line upstream of the solvent flow and distal from the suction device), said devices may be efficiently protected while still being fully functional. For example, the gas supply may be important to assure a condensation-free run of the degasser. Further, the sensor device may be important to regulate to the set pressure (vacuum).

[0035] Furthermore, the coupling of the degasser chambers to the fluid line via individual coupling points, wherein the suction device is not coupled at a central point (compare Figures 4 and 5) but is coupled to an extremity of the flow line, avoids contamination (cross-flow, diffusion) between the gases (of different solvents) of different degasser chambers. This prevention of contamination may be further supported by the gas flow from the gas supply. In summary, the disclosure may combine the advantages of contamination-free degasser chambers and well-protected sensor and gas supplies into one and the same architecture. EXEMPLARY EMBODIMENTS

[0036] In an embodiment, the suction device is coupled to the fluid line at a suction coupling point. In an embodiment, the suction coupling point is arranged at the first coupling point or in fluid streaming direction downstream of the first coupling point. The suction coupling point can be at the first coupling point or separate from the first coupling point. Preferably, the suction coupling point is in fluid main streaming direction downstream of the degasser chamber coupling points. In other words, the suction coupling point may not be a central coupling point (compare Figures 4 and 5). Thereby, cross-flow of gas between the degasser chambers may be efficiently avoided.

[0037] In an embodiment, the suction device is configured to suck the fluid from the first degasser chamber and the second degasser chamber along the fluid line in (main) fluid streaming direction downstream. Thereby, gas may be efficiently removed from the degasser chambers.

[0038] In an embodiment, the second coupling point is arranged in fluid streaming direction upstream of the first coupling point. Thus, the degasser chamber coupling points are spatially separate and arranged along the (common) fluid line, thereby the movement of solvent vapors from one degasser chamber to another is avoided (cross-flow).

[0039] In an embodiment, the sensor line is coupled in fluid streaming direction upstream of the fluid line to the fluid line at the second coupling point. This may provide the advantage that the sensor line (with the coupled sensor device and gas supply) may be a protected region, (essentially) of the gas flow (not reached by the solvent vapors) originating from the degasser chambers.

[0040] In an embodiment, the sensor device is coupled to the sensor line at a sensor coupling point arranged fluid upstream of the second coupling point. In an embodiment, the gas supply is coupled to the sensor line at a gas coupling point. Thus, the sensor device and / or the gas supply are coupled to a region upstream of the degasser chambers, so that the flow from the degasser chambers does not come in contact with the devices coupled to the sensor line.

[0041] In an embodiment, the second coupling point is the most upstream / distal coupling point of the fluid line with respect to the first coupling point. Hence, the second coupling point may define the upstream end of a degasser chamber region of the flow line, being different from a sensor line region of the flow line.

[0042] In an embodiment, the second coupling point is different from the first coupling point. Separation of the degasser chamber coupling points may prevent cross-flow between the degasser chambers.

[0043] In an embodiment, the gas coupling point is arranged at at least one of the following: the second coupling point, upstream of the sensor coupling point, downstream of the sensor coupling point, at the sensor coupling point (compare Figure 3). Thereby, a high design flexibility (depending on the desired application) is provided. In any case, the gas supply may be well-protected from harmful gases from the degasser chambers.

[0044] In an embodiment, the sensor line is free of a coupling point that is coupled to a degasser chamber (sensor device not directly connected to degasser chamber). In other words, the sensor line is in a region (of the flow line) that is shifted (upstream) with respect to the degasser chambers.

[0045] In an embodiment, the sensor line is configured as a part of the fluid line. Costs and efforts may be saved, when the sensor line is configured as a part of the already present flow line. In this case, a main flow line region or a degasser chamber flow line region may be defined as well as a sensor line flow line region.

[0046] In an embodiment, the degasser further comprises a third degassing chamber coupled to the fluid line at a third coupling point, wherein the third coupling point is arranged between the first coupling point and the second coupling point.

[0047] In an embodiment, the degasser further comprises: a fourth degassing chamber coupled to the fluid line at a fourth coupling point, wherein the fourth coupling point is arranged between the third coupling point and the second coupling point.

[0048] Hence, a plurality of degasser chambers may be coupled to the flow line in between the first coupling point and the second coupling point (defining the borders of the degasser chamber flow line region). Preferably, the degasser chamber coupling points are arranged separately along the flow line (in series) to avoid cross-flow between the degasser chambers.

[0049] In an embodiment, the suction device is configured as a vacuum pump for providing a vacuum in the fluid line and / or the degasser chambers. In an embodiment, the degasser chambers are configured as vacuum degasser chambers. In an embodiment, the fluid line is configured as a vacuum line. In an embodiment, the degasser chambers are configured for degassing a respective mobile phase and / or a sample associated with the analytical device. Thus, established and reliable techniques can be directly applied to the described degasser.

[0050] In an embodiment, the gas supply comprises at least one of: an opening, an aperture, a restriction, an inlet, a vent, a channel, a conduit. A plurality of advantageous designs are possible for the gas supply (device), depending on the desired application.

[0051] In an embodiment, the gas supply is configured to enable streaming, in particular streaming of a defined / controlled / regulated amount, of a gas, in particular air, from exterior into the fluid line and / or sensor line. In an embodiment, the gas supply comprises at least one of the following features: a filter, a valve, in particular an active valve or a passive valve, an adjustable restriction element for adjusting an opening diameter of the gas inlet, one or more openings. In an embodiment, the gas supply comprises a coupling to a gas source. Thereby, a plurality of different gases may be supplied, for example at least one of oxygen, nitrogen, a noble gas. The gas supply can for example prevent condensation along the flow line and / or in the degasser chambers.

[0052] In an embodiment, the sensor coupling point is arranged at least 1 mm, in particular at least 3 mm, away in the (main) fluid streaming direction upstream from the second coupling point. By keeping , it may be ensured, that the sensor device is well protected from the vapors from the degasser chambers.

[0053] In an embodiment, the degasser further comprises a further suction device, coupled to the fluid line, in particular at or in fluid streaming direction downstream of the second coupling point. In an embodiment, the degasser (in particular the suction device) is configured to provide a pressure in the range 10 to 900 mbar. This may enable an efficient run of the degasser.

[0054] In an embodiment, the degasser is configured so that a fluidic cross-flow (diffusion) between the first degasser chamber and the second degasser chamber is suppressed / prevented. Thus, a migration of gas of (organic) solvents between degasser chambers may be suppressed. This may be done in particular by the gas flow from the gas supply and / or the positioning of the degasser chamber coupling points in series.

[0055] In an embodiment, the method further comprises: providing a vacuum in the fluid line and the degasser chambers by the suction device. In an embodiment, the method further comprises: degassing a first mobile phase in the first degasser chamber, and / or degassing a second mobile phase in the second degasser chamber. In an embodiment, the first mobile phase is different from the second mobile phase.

[0056] In an embodiment, the mobile phase comprises a fluid being harmful / aggressive for a sensor device and / or a gas supply (device). In particular a gas (eventually a gas-liquid mixture; a solvent vapor) of an organic solvent (from the mobile phase) may be harmful. Examples of organic solvents used in HPLC may include acetonitrile, methanol, tetrahydrofuran, ethanol, hexane, isopropanol, toluene.

[0057] In an embodiment, the analytical device is configured as a sample separation device, in particular a fluidic chromatography device, more in particular a HPLC device.

[0058] In one embodiment, the sample separation device further comprises: a mixing point, where a sample is injected into the solvent, wherein the fluid compartment (the analytical device) is arranged upstream or downstream of the mixing point.

[0059] In one embodiment, the sample separation device further comprises: a solvent mixing point, where at least two solvent portions may be mixed, wherein the fluid compartment (the analytical device) is arranged upstream or downstream of the solvent mixing point.

[0060] In one embodiment, the sample separation device further comprises: a solvent drive, configured to drive the solvent as a mobile phase, wherein the fluid compartment (the analytical device) is arranged upstream or downstream of the solvent drive.

[0061] It becomes aware from the embodiments described directly above, that there is a high design flexibility regarding where the fluid compartment can be located in the analytical device / sample separation device. Depending on the present circumstances and the applied measurement method, different locations may be specifically favorable.

[0062] In one embodiment, the chromatography device comprises a mobile phase (solvent) drive and a separating device, wherein the mobile phase drive is configured for driving a mobile phase through the separating device, and the separating device is configured for chromatographically separating compounds of a sample fluid in the mobile phase.

[0063] In one embodiment, the analytical device and / or the sample separation device comprises a liquid chromatography system, wherein the sample fluid is a sample liquid, the mobile phase is comprised of one or more liquid solvents, and the separating device is a chromatographic column configured for separating compounds of the sample dissolved in the mobile phase.

[0064] In one embodiment, the chromatography device is a fluidic chromatography device, in particular a HPLC device.

[0065] Embodiments of the present disclosure might be embodied based on most conventionally available HPLC systems, such as the Agilent 1220, 1260 and 1290 Infinity LC Series (provided by the applicant Agilent Technologies).

[0066] The separating device preferably comprises a chromatographic column providing the stationary phase. The column might be a glass, metal, ceramic or a composite material tube (e.g. with a diameter from 50 pm to 5 mm and a length of 1 cm to 1 m) or a microfluidic column (as disclosed e.g. in EP 1577012 A1 or the Agilent 1200 Series HPLC-Chip / MS System provided by the applicant Agilent Technologies). 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 at least partly separated from each other. 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.

[0067] The mobile phase (or eluent) can be either a pure solvent or a mixture of different solvents. It can also contain additives, i.e. be a solution of the said additives in a solvent or a mixture of solvents. It can be chosen e.g. to adjust the retention of the compounds of interest and / or the amount of mobile phase to run the chromatography. The mobile phase can also be chosen so that the different compounds can be separated effectively. The mobile phase might comprise an organic solvent like e.g. methanol or acetonitrile, often diluted with water. For gradient operation water and organic solvent is delivered in separate containers, 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.

[0068] The sample fluid 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, bio reactor, digestion, or other type of sample preparation.

[0069] The fluid is preferably a liquid but may also be or comprise a gas and / or a supercritical fluid (as e.g. used in supercritical fluid chromatography - SFC - as disclosed e.g. in US 4,982,597 A).

[0070] The pressure in the mobile phase might range from 2-200 MPa (20 to 2000 bar), in particular 10-150 MPa (100 to 1500 bar), and more particular 50-130 MPa (500 to 1300 bar).

[0071] The HPLC system might further comprise 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. Further details of HPLC system are disclosed with respect to the aforementioned Agilent HPLC series, provided by the applicant Agilent Technologies. BRIEF DESCRIPTION OF DRAWINGS

[0072] Other objects and many of the attendant advantages of embodiments of the present disclosure will be readily appreciated and become better understood by reference to the following more detailed description of embodiments in connection with the accompanied drawings. Features that are substantially or functionally equal or similar will be referred to by the same reference signs.

[0073] Figure 1 illustrates an analytical device implemented as a liquid chromatography device with a degasser, according to an exemplary embodiment.

[0074] Figure 2 illustrates a degasser with two degassing chambers, according to an exemplary embodiment of the invention.

[0075] Figure 3 illustrates a degasser with four degassing chambers and three gas supplies, according to an exemplary embodiment of the invention.

[0076] Figures 4 and 5 respectively illustrate a conventional degasser. DETAILED DESCRIPTION OF DRAWINGS

[0077] Referring now in greater detail to the drawings, Figure 1 depicts a general schematic of an analytical device 10, implemented here as a high performance liquid chromatography (HPLC) device. A solvent drive 20 (such as a pump, can be used as a pressurizing device) receives a solvent as the mobile phase from a solvent supply 25. The solvent drive 20 drives the mobile phase through a separating device 30 (such as a chromatographic column), which can be seen here as the analytical domain of the device. A sample injector 40 (also referred to as sampler, sampling space, sample - 15 - introduction apparatus, sample dispatcher, etc.) is provided between the solvent drive 20 and the separating device 30 in order to subject or add (often referred to as sample introduction) portions of one or more sample fluids into the flow of a mobile phase at a mixing point 95. The separating device 30 is adapted for separating compounds of the sample fluid, e.g. a liquid. A detector 50 is provided for detecting separated compounds of the sample fluid. A fractionating unit 60 can be provided for outputting separated compounds of sample fluid. In one embodiment, at least parts of the sample injector 40 and the fractionating unit 60 can be combined, e.g. in the sense that some common hardware is used as applied by both of the sample injector 40 and the fractionating unit 60.

[0078] The separating device 30 may comprise a stationary phase configured for separating compounds of the sample fluid. Alternatively, the separating device 30 may be based on a different separation principle (e.g. field flow fractionation).

[0079] While the mobile phase can comprise one solvent only, it may also be mixed of plurality of solvents (solvent supply 25). Such mixing might be a low pressure mixing and provided upstream of the solvent drive 20, so that the solvent drive 20 already receives and pumps the mixed solvents as the mobile phase. Alternatively, the solvent drive 20 might comprise plural individual pumping units, with plural of the pumping units each receiving and pumping a different solvent or mixture, so that the mixing of the mobile phase (as received by the separating device 30) occurs at high pressure and downstream of the mobile phase drive 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.

[0080] A data processing device (control device) 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 analytical device 10 in order to receive information and / or control operation.

[0081] Further in Figure 1, the structure of a degasser 100 for degassing the mobile phase (from solvent supply 25) is illustrated. The degasser 100 contains a degasser chamber with a degasser volume 102 which is delimited therein. In this degasser volume 102 of the degasser chamber, a degassing membrane 104 is accommodated. The degassing membrane 104 is arranged between a mobile phase - 16 - supply 106 for supplying a mobile phase to be degassed and a mobile phase discharge 108 for discharging the degassed mobile phase.

[0082] For example, the mobile phase supply 106 may be a channel / hose which delivers the mobile phase from the liquid reservoir 25 to the degassing membrane 104 . For example, the degassing membrane 104 may be configured as a semi-permeable hose portion which is connected to the hose of the mobile phase supply 106 . The mobile phase discharge 108 may also be a hose which delivers the degassed mobile phase from the degassing membrane 104 to the fluid drive 20.

[0083] At the degassing membrane 104, the gas which is to be removed from the liquid of the mobile phase may pass through the degassing membrane 104 into the degasser volume 102. An additional phenomenon is that, to a certain extent, also the liquid of the mobile phase may pass through the degassing membrane 104 into the degasser volume 102 (e.g. as a gas-liquid mixture). Therefore, in the degasser volume 102, during the operation, both, gas which is desirably removed from the mobile phase and eventually an unavoidable amount of solvent of the liquid mobile phase, may be present.

[0084] Figure 1 further shows a suction device 110 which is connected to the degasser chamber vias a suction device line 116. The suction device 110 sucks the gas which passed through the degassing membrane 104 and the vapor. This leads to effectively degassing the mobile phase in the degasser 100.

[0085] Figure 2 illustrates a degasser 100 with two degassing chambers 120,130, according to an exemplary embodiment of the invention. The degasser 100 comprises a fluid line 150 for streaming fluid along a main fluid stream direction towards the suction device 110, here a vacuum pump. The first degasser chamber 120 (e.g. configured as described for Figure 1) is coupled to the fluid line 150 at a first coupling point 121. The suction device 110 is coupled in this example also to the fluid line 150 via the first coupling point 111,121 so that the first coupling point 121 also serves as a suction coupling point 121. Yet, in another example, the first coupling point 121 and the suction coupling point 111 can be spatially separated. The suction coupling point 111 can be at / on the fluid line 150 or fluidically couple with the fluid line 150. The second degasser chamber 130 is coupled to the fluid line 150 at a second coupling point 131 being different from the first coupling point 121. With respect to the main - 17 - fluid stream direction along the fluid line 150 towards the suction device 110, the second coupling point 131 is arranged upstream of the first coupling point 121. The suction coupling point 111 is arranged at the first coupling point 121 or in main fluid streaming direction downstream of the first coupling point 121, and the second coupling point 131 is arranged in fluid streaming direction upstream of the first coupling point 121.

[0086] The suction device 110 is configured to suck fluid (gas) from the first degasser chamber 120 and the second degasser chamber 130. First fluid from the first degasser chamber 120 flows in a first minor stream along a first degasser line 122 and joins the main fluid stream of the flow line 150 at the first coupling point 121. Second fluid from the second degasser chamber 130 flows in a second minor stream along a second degasser line 132 and joins the main fluid stream of the flow line 150 at the second coupling point 131.

[0087] The degasser 100 further comprises a sensor line 165, coupled to the fluid line 150. In this example, the sensor line 165 is a part of the fluid line 150 and the sensor line 165 can be defined as being coupled to the (rest of the) fluid line 150 at the second coupling point 131. In other words, the sensor line 165 is coupled to the fluid line 150 in main fluid streaming direction upstream of the degasser chamber coupling points 121, 131. A sensor device 160, in particular a pressure sensor, is coupled to the sensor line 165 at a sensor coupling point 161. In this manner, the sensor device 160 is coupled to the fluid line 150 at a position that is free of gas (in particular gas of organic solvents) from the degasser chambers 120,130. Specifically, the minor fluid streams from the degasser chambers 120, 130 join the main fluid stream in the flow line 150 already downstream of the sensor device 160. Thereby, the sensor device 160 can efficiently measure the pressure in the flow line 150 but is at the same time protected from organic solvent gases of the mobile phase that can harm / damage the sensor device 160.

[0088] The degasser 100 comprises a gas supply 170 that is also coupled to the sensor line 165 at a gas coupling point 171. The gas supply 170 provides a gas flow from the exterior into the (sensor line 165 and the) flow line 150. The gas flow can also enter (via minor streams) the degasser chambers 120, 130 in an example. The gas supply 170 can be realized as one of an opening (or a plurality of openings), a vent, a pump, etc. The gas supply 170 can have a filter and / or an active / passive valve. While in an embodiment, the gas supply 170 merely supplies ambient air, in another embodiment, the gas supply 170 can be coupled to a gas source and provide e.g. one of nitrogen or a noble gas. The gas coupling point 171 is arranged in this example in main fluid streaming direction upstream of the sensor coupling point 161. Nevertheless, in other embodiments, the gas coupling point 171 can also be arranged in main fluid streaming direction downstream or even at the sensor coupling point 161. Like the sensor device 160, the gas supply 170 is also arranged distal to the degasser chamber coupling points 121, 131 and thus protected from organic solvent gas / vapor of the mobile phases.

[0089] Figure 3 illustrates a degasser with four degassing chambers 120, 130, 140, 145 and three gas supplies 170, 170’, 170”, according to an exemplary embodiment of the invention. The configuration is comparable to the one described for Figure 2, yet a third degasser chamber 140 is coupled to the fluid line 150 at a third coupling point 141 and a fourth degasser chamber 145 is coupled to the fluid line 150 at a fourth coupling point 146. The third degasser coupling point 141 and the fourth degasser coupling point 146 are arranged in between the first coupling point 121 and the second coupling point 131, so that the second coupling point 131 is the most distal degasser chamber coupling point with respect to the suction device 110. The second coupling point 131 may hence be seen as a coupling point between the fluid line 150 and the sensor line 165. All degasser chamber coupling points 121,131, 141, 146 are arranged in series along the flow line 150.

[0090] In this example, three different positions of the gas supply 170 can be seen. A first gas supply 170 is coupled at a first gas coupling point 171 at the interface between fluid line 150 and sensor line 165. Here, the second coupling point 131 serves at the same time as the first gas coupling point 171. A second gas supply 170’ is coupled at a second gas coupling point 171’ to the sensor line 165, wherein the second gas coupling point 171’ is arranged between the second coupling point 131 and the sensor coupling point 161. In other words, upstream of the second coupling point 131 and downstream of the sensor coupling point 161. Finally, a third gas supply 170” is coupled at a third gas coupling point 171 ” to the sensor line 165, wherein the third gas coupling point 171” is arranged in main fluid streaming direction upstream of the sensor coupling point 161. In this example, the main fluid stream can be defined - 19 - as from the third gas coupling point 171” to the suction device 110. [0091 ] Additionally, it is illustrated in Figure 3, that a respective mobile phase fluid line is passing through each of the degasser chambers 120, 130, 140, 145. As described for Figure 1, each degasser chamber comprises a degasser volume 102 with a membrane 104. Mobile phase is streamed from a supply 106 to a discharge 108, while gas (also organic solvent gas) diffuses through the membrane 104, thereby degassing the respective mobile phase.

[0092] Reference signs 10 Analytical device 20 Solvent drive 25 Solvent supply 30 Separating device 40 Sample injector 45 Mixing point 50 Detector 60 Fractionating unit 70 Data processing device, control unit / device 100 Degasser 102 Degasser volume 104 Degasser membrane 106 Mobile phase supply 108 Mobile phase discharge 110 Suction device 111 Suction coupling point 116 Suction device line 120 First degasser chamber 121 First coupling point 122 First degasser line, first minor fluid stream 130 Second degasser chamber 131 Second coupling point 132 Second degasser line, second minor fluid stream 140 Third degasser chamber 141 Third coupling point 145 Fourth degasser chamber 146 Fourth coupling point 150 Fluid line, main fluid stream 5 160 Sensor device 161 Sensor coupling point 165 Sensor line 170 Gas supply 171 Gas coupling point 10 15

Claims

1. A degasser (100), in particular for an analytical device (10), comprising:a fluid line (150);a first degasser chamber (120) coupled to the fluid line (150) at a first coupling point (121);a second degasser chamber (130) coupled to the fluid line (150) at a second coupling point (131);a suction device (110), in particular a vacuum pump, coupled to the fluid line (150) to suck fluid from the first degasser chamber (120) and the second degasser chamber (130);a sensor line (165) coupled to the fluid line (150);a sensor device (160), in particular a pressure sensor, coupled to the sensor line (165); anda gas supply (170) coupled to the sensor line (165).

2. The degasser (100) according to claim 1, further comprising at least one of the following features:wherein the suction device (110) is coupled to the fluid line (150) at a suction coupling point (111);wherein the suction device (110) is configured to suck the fluid from the first degasser chamber (120) and the second degasser chamber (130) along the fluid line (150) in fluid streaming direction downstream;wherein the suction coupling point (111) is arranged at the first coupling point (121) or in fluid streaming direction downstream of the first coupling point (121);wherein the second coupling point (131) is arranged in fluid streaming direction upstream of the first coupling point (121);wherein the sensor line (165) is coupled in fluid streaming direction upstream of the fluid line (150) to the fluid line (150) at the second coupling point (121);wherein the sensor device (160) is coupled to the sensor line (165) at a sensor coupling point (161) arranged fluid upstream of the second coupling point (121);wherein the gas supply (170) is coupled to the sensor line (165) at a gas coupling point (171);wherein the second coupling point (131) is the most upstream / distal coupling point of the fluid line (150) with respect to the first coupling point (121).

3. The degasser (100) according to claim 1 or 2,wherein the second coupling point (131) is different from the first coupling point (121).

4. The degasser (100) according to one of the preceding claims,wherein the gas coupling point (171) is arranged at at least one of the following:the second coupling point (131),upstream of the sensor coupling point (161);downstream of the sensor coupling point (161);at the sensor coupling point (161).

5. The degasser (100) according to one of the preceding claims, wherein the sensor line (165) is free of a coupling point that is coupled to a degasser chamber.

6. The degasser (100) according to one of the preceding claims,wherein the sensor line (165) is configured as a part of the fluid line (150).

7. The degasser (100) according to one of the preceding claims, further comprising:a third degassing chamber (140) coupled to the fluid line (150) at a third coupling point (141), wherein the third coupling point (141) is arranged between the first coupling point (121) and the second coupling point (131),in particular further comprising:a fourth degassing chamber (145) coupled to the fluid line (150) at a fourth coupling point (146), wherein the fourth coupling point (146) is arranged between the third coupling point (141) and the second coupling point (131).

8. The degasser (100) according to one of the preceding claims, comprising at least one of the following features:wherein the suction device (110) is configured as a vacuum pump for providing a vacuum in the fluid line (150) and / or the degasser chambers (120, 130, 140, 145);wherein the degasser chambers (120,130,140,145) are configured as vacuum degasser chambers;wherein the fluid line (150) is configured as a vacuum line;wherein the degasser chambers (120, 130, 140, 145) are configured for degassing a respective mobile phase and / or a sample associated with the analytical device (10).

9. The degasser (100) according to one of the preceding claims,wherein the gas supply (170) comprises at least one of: an opening, an aperture, a restriction, an inlet, a vent, a channel, a conduit.

10. The degasser (100) according to one of the preceding claims,wherein the gas supply (170) is configured to enable streaming, in particular a defined amount, of a gas, in particular air, from exterior into the fluid line (150) and / or sensor line (165).

11. The degasser (100) according to one of the preceding claims,wherein the gas supply (170) comprises at least one of the following features: a filter, a valve, in particular an active valve or a passive valve, one or a more openings, a coupling to a gas source, in particular supplying at least one of oxygen, nitrogen, a noble gas.

12. The degasser (100) according to one of the preceding claims,wherein the sensor coupling point (165) is arranged at least 1 mm, in particular at least 3 mm, away in the fluid streaming direction upstream from the second coupling point (131).

13. The degasser (100) according to one of the preceding claims,further comprising: a further suction device, coupled to the fluid line (150), in particular at or in fluid streaming direction downstream of the second coupling point (131); and / orconfigured to provide a pressure in the range 50 to 500 mbar.

14. The degasser (100) according to one of the preceding claims,configured so that a fluidic cross-flow between the first degasser chamber (120) and the second degasser chamber (130) is suppressed, in particular prevented.

15. An analytical device (10) for analyzing a fluidic sample, wherein the analytical device (10) comprises:a degasser (100) according to one of the preceding claims, in particular for degassing at least part of a mobile phase and / or a sample.

16. The analytical device (10) according to claim 15, configured as a sample separation device, in particular comprising at least one of the following features:the sample separation device (10) is configured as a chromatography sample separation apparatus, in particular a liquid chromatography sample separation apparatus, a high-performance liquid chromatography sample separation apparatus, a gas chromatography sample separation apparatus or asupercritical fluid chromatography sample separation apparatus;a sample separation unit (30) configured as a chromatographic separation column;an injector (40) configured to inject the fluidic sample into the mobile phase;a fractioner unit (60) configured to collect the separated fluidic sample.

17. A method for operating a degasser (100) according to one of the preceding claims 1 to 14, the method comprising:sucking the fluid along the fluid line (150) from the first degasser chamber (120) and the second degasser chamber (130) towards the suction device (110) in fluid streaming direction downstream;sensing a parameter, in particular pressure, by the sensor device (160) upstream of the streaming fluid; andsupplying gas by the gas supply (170), in particular to the streaming fluid.

18. The method according to claim 17, further comprising:providing a vacuum in the fluid line (150) and the degasser chambers (120,130, 140,145) by the suction device (110).

19. The method according to claim 17 or 18, further comprising:degassing a first mobile phase in the first degasser chamber (120), and / or degassing a second mobile phase in the second degasser chamber (130),in particular wherein the first mobile phase is different from the second mobile phase.

20. The method according to one of the claims 17 to 19,wherein the mobile phase comprises a fluid, in particular an organic solvent, being harmful for a sensor device (160) and / or a gas supply (170), in particular at least one of acetonitrile, methanol, tetrahydrofuran, ethanol, hexane, isopropanol, toluene.27

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