DE102021119855A1 - Fluid supply device with buffer tank for bridging an interrupted fluid supply - Google Patents

Abstract

Fluid supply device (100) for supplying a fluid conveying device (20) of a sample separation device (10) with a mobile phase from at least one mobile phase container (102), the fluid supply device (100) having a buffer container (104) for storing a buffer amount of mobile phase in or on a fluidic path between the at least one mobile phase container (102) and the fluid conveying device (20), and a bridging mechanism (106) for temporarily supplying the fluid conveying device (20) with mobile phase from the buffer container (104) when the at least one mobile phase container (102) is temporarily decoupled from the provision of the mobile phase.

Description

TECHNICAL BACKGROUND

The present invention relates to a fluid supply device for supplying a fluid delivery device of a sample separation device with a mobile phase from at least one mobile phase container, a sample separation device, and a method for supplying a fluid delivery device of a sample separation device with a mobile phase from at least one mobile phase container.

In an HPLC, a liquid (mobile phase) is typically used at a very precisely controlled flow rate (for example in the range from microliters to milliliters per minute) and at a high pressure (typically 20 to 1000 bar and beyond, currently up to 2000 bar) , in which the compressibility of the liquid can be felt, is moved through an adsorption medium as a stationary phase (for example in a chromatographic column) in order to separate individual components of a sample liquid introduced into the mobile phase. Such an HPLC system is known, for example, from EP 0,309,596 B1 by the same applicant, Agilent Technologies, Inc.

A reliable supply of mobile phase is of the utmost importance for a good separation result with a sample separation device.

EPIPHANY

It is an object of the invention to ensure a reliable supply of mobile phase in a fluid supply device. The object is achieved by means of the independent claims. Further embodiments are shown in the dependent claims.

According to an exemplary embodiment of the present invention, a fluid supply device for supplying a fluid conveying device of a sample separation device with a mobile phase from at least one mobile phase container is created, wherein the fluid supply device comprises a buffer container for storing a buffer amount of mobile phase in a fluidic path (if, for example, the buffer container is from mobile phase Phase is traversed on the way from the mobile phase container to the fluid delivery device, see for example 2 ) or on a fluidic path (if, for example, the buffer container is arranged in a side arm branching off from the fluidic path and is therefore fluidically coupled to the mobile phase from the mobile phase container without the mobile phase flowing through it on the way from the mobile phase container to the fluid conveying device, see for example 6th ) between the at least one mobile phase container and the fluid conveying device, and a bridging mechanism for temporarily supplying the fluid conveying device with mobile phase from the buffer container when the at least one mobile phase container is temporarily decoupled from the provision of mobile phase.

According to another exemplary embodiment of the present invention, a sample separation device for separating a sample in a mobile phase is provided, the sample separation device having a fluid conveying device for conveying the sample and the mobile phase into which the sample is to be introduced, a sample separating device for separating the in the mobile phase Phase introduced sample, and a fluid supply device with the features described above for supplying the fluid delivery device with mobile phase from at least one mobile phase container.

According to yet another exemplary embodiment of the present invention, a method for supplying a fluid conveying device of a sample separation device with a mobile phase from at least one mobile phase container is provided, the method storing a buffer amount of mobile phase in a buffer container in or on a fluidic path between the at least a mobile phase container and the fluid conveying device, and a temporary supply of the fluid conveying device with mobile phase from the buffer container when the at least one mobile phase container is temporarily decoupled from the provision of mobile phase.

In the context of the present application, the term “sample separation device” can in particular denote a device which is able and configured to separate a (in particular fluidic) sample, in particular to separate it into different fractions. For example, the sample can be separated by means of chromatography or electrophoresis. For example, the sample separator can be a liquid chromatography sample separator.

In the context of the present application, the term “sample” is understood to mean, in particular, a medium that contains the matter actually to be analyzed (for example a biological sample such as a protein solution, a pharmaceutical sample, etc.). A fluidic sample can be a sample that has a liquid and / or a gas, optionally additionally having solid particles. According to exemplary embodiments, solid samples can also be subjected to a separation process.

In the context of the present application, the term “mobile phase” is understood to mean in particular a fluid (further in particular a liquid) which serves as a carrier medium for transporting the sample from the fluid drive device to the sample separation device. For example, the mobile phase can be a solvent (e.g. organic and / or inorganic) or a solvent composition (e.g. water and ethanol).

In the context of the present application, the term “fluid conveying device” can in particular mean a device for conveying a fluid (in particular a mobile phase and / or a (in particular fluidic) sample) under pressure (in particular under high pressure, further in particular under a pressure of at least 1000 bar ) can be understood. In particular, a fluid delivery device can be a piston pump which is designed to deliver the fluid by reciprocating at least one piston. For example, such a fluid delivery device can be a high pressure chromatography pump.

In the context of this application, the term “sample separator” is understood to mean, in particular, a component that can be inserted into a sample separator and, when operating the sample separator alone or in conjunction with other components, separates a (particularly fluid) sample into different components. In particular, such a sample separation device can be a chromatography separation column or a component for electrophoresis separation. A chromatography separation column, for example, can have a container filled with a stationary phase, the stationary phase being able to adsorb different components of the (particularly fluid) sample when the (in particular fluid) sample flows through between an inlet and an outlet (i.e. between two fluid connection points) . The stationary phase can furthermore be designed to desorb or detach the adsorbed components fractionally, in particular depending on a mobile phase flowing through the sample separation device in the form of a solvent composition.

In the context of this application, the term “mobile phase container” is understood in particular to mean a reservoir from which a fluid delivery device is provided with mobile phase for use in connection with a separation of a sample in a sample separation device. For example, a mobile phase container can be a solvent bottle that is fluidically coupled to or in the fluid supply device via a fluid line (for example a hose or capillary connection), via a receiving station or the like.

In the context of this application, the term “buffer container” is understood to mean in particular a circumferentially limited container body, inside of which a (in particular defined maximum) buffer volume for temporarily storing mobile phase for use as required for mobile phase supply of a fluid delivery device is formed. Such a buffer container can be fluidically coupled to other components in a fluid supply device, for example via connected fluid lines. A buffer container can in particular be implemented as an additional component between fluid lines (such as a capillary or hose connection) in a fluid supply device. In particular, such a buffer container can have a significantly larger inside diameter than a connected fluid line, for example at least twice or at least three times the inside diameter.

In the context of this application, the term “bridging mechanism for temporarily supplying the fluid delivery device with mobile phase from the buffer container when the at least one mobile phase container is temporarily decoupled from the provision of mobile phase” is understood in particular to mean an active or passive apparatus mechanism which, in the event of a temporary interruption of a Supply of mobile phase from one or more mobile phase containers maintains an uninterrupted mobile phase supply to the fluid conveying device by using mobile phase contained in the buffer container in the interruption period to supply the fluid conveying device with mobile phase.

According to an exemplary embodiment of the invention, a fluid supply device for a sample separation device (for example for an HPLC) can be provided which can continuously supply a fluid delivery device (for example a chromatographic high pressure pump) with mobile phase for performing a sample separation even if a standard supply with mobile phase from one or more mobile phase containers (e.g. solvent containers with different solvents) is temporarily interrupted. For this purpose, a buffer container can be provided in the fluid supply device, which has a sufficiently large internal volume with a buffer capacity for particularly repeatable emptying and filling and can maintain a mobile phase supply while the mobile phase supply from the mobile phase container is temporarily interrupted or until this mobile phase supply (again) is made. This can result in a Fluid supply device a reliable supply of mobile phase can be ensured. In this way, a continuous supply of a sample separation device with mobile phase can be made possible, even if - for example when replacing an emptied mobile phase container or when a mobile phase container is temporarily decoupled from a fluid delivery device for reasons of pressure limitation - a mobile phase container cannot currently be used for fluid supply or should. This can ensure, for example, that during a separation run for separating a fluidic sample in a sample separation device using mobile phase, the separation run can be continued and preferably ended, even if a fluid supply from a mobile phase container is temporarily interrupted. As a result, an undesired interruption of a separation run due to a lack of mobile phase can be suppressed or even avoided entirely. In addition, by temporarily bridging an interrupted mobile phase supply from a mobile phase container, undesired penetration of air bubbles into a sample separation device can be avoided and thereby an uninterrupted supply of the sample separation device with mobile phase can be ensured. Such an undesired entry of air bubbles can conventionally occur when, during an exchange of a mobile phase container, the fluid drive device sucks in ambient air through a fluid line which is temporarily separated from the mobile phase container to be exchanged.

Additional configurations of the fluid supply device, the method and the sample separation device are described below.

According to one embodiment, the bridging mechanism can be designed to temporarily supply the fluid delivery device with mobile phase from the buffer container when a supply of the fluid delivery device with mobile phase from the at least one mobile phase container is temporarily interrupted, in particular during an exchange of the at least one mobile phase container. If a mobile phase container (for example a solvent bottle) has become empty, a user can replace it with a filled mobile phase container. During the exchange, this mobile phase container is therefore temporarily unavailable for supplying the fluid delivery device with mobile phase. In this intermediate interval, the mobile phase previously filled into the buffer container can be used for further supply of the fluid delivery device. This intermediate supply state can be activated, for example (for example by a user or by a control device) in that a valve between the mobile phase container and the buffer container is closed as long as the replacement of the mobile phase container continues.

According to an alternative or supplementary embodiment, the bridging mechanism can be designed to temporarily supply the fluid delivery device with mobile phase from the buffer container in order to reduce an excessive pressure caused by the at least one mobile phase container. One or more components downstream of the buffer container (for example a fluid delivery device) can be susceptible to wear and / or failure if the pressure acting on them becomes excessively high. For example, a mobile phase container still almost completely filled with mobile phase can exert considerable pressure on the system. If such a pressure exceeds a permitted or desirable value or range, the mobile phase container can temporarily be fluidically decoupled from the buffer container, which can result in a pressure reduction. The buffer container can also function in such an interval to maintain the mobile phase supply of the fluid delivery device.

According to one embodiment, the fluid supply device can have a closing device which is designed for, in particular automatic or user-defined, closing of a fluid connection between the at least one mobile phase container and the buffer container, in particular when fluidically separating the at least one mobile phase container from the fluid supply device. For example, the closing device can be a fluid valve which can optionally allow or prevent a fluid connection between the mobile phase container and the buffer container. Such a fluid valve can be actuated, for example, by a user (who wishes to exchange the mobile phase container, for example). Alternatively, such a fluid valve can prevent a fluid connection when a mobile phase container, for example mounted upside down, is removed from a receiving station for changing. However, it is also possible for the closing device to be integrated in a detachable fitting which normally fluidically couples a mobile phase container to the buffer container and fluidically decouples it when the fitting is separated. With such a closure device, in particular, undesired introduction of an air bubble into the sample separation device can be prevented when, for example, a mobile phase container is exchanged.

According to one embodiment, the buffer container can have a flexibly changeable receiving volume. In other words, the receiving volume of the buffer container can be based on and / or based on the pressure conditions be variable on a current mobile phase supply or discharge. The buffer container can advantageously breathe clearly in order to be able to adapt to the current fluid and pressure conditions. For example, the buffer container can expand when the mobile phase is filled into the buffer container and can contract when the mobile phase is discharged from the buffer container.

According to one embodiment, the buffer container can have or consist of an elastic material (see for example 11 and 12th ). For example, the buffer container can have a wall made of rubber or silicone. An elastic buffer container can expand its buffer volume when mobile phase is filled into the buffer container and can reduce its buffer volume when mobile phase is removed from the buffer container.

According to one embodiment, the buffer container can have a variable shape, in particular a bellows shape (see for example 9 and 10 ). For example, such a buffer container can unfold into an expanded configuration when mobile phase is supplied and can collapse into a contracted configuration when mobile phase is withdrawn from the buffer container for liquid supply.

According to one exemplary embodiment, the fluid supply device can have a body that can be moved in order to change the receiving volume of the buffer container, in particular a movable piston or a movable membrane or a movable plate, in the buffer container (see for example 13th and 14th ). The movement of the movable body can in particular be actively controlled, for example by a user or an actuator. If the movable body moves in the backward direction in the buffer container, the buffer volume can be increased, in the opposite case it can be decreased.

According to one embodiment, the buffer container can be designed to store a maximum amount of buffer of mobile phase of at least 1 ml, in particular at least 3 ml, further in particular at least 5 ml. An intermediate supply state fed by the mobile phase in the buffer container can be triggered, for example (for example by a user or by a control device) by closing a valve between the mobile phase container and the buffer container as long as the mobile phase container is being replaced. The exchange of a mobile phase container by a user usually takes less than 1 minute. The buffer volume of the buffer container can be based on a predetermined flow rate of the mobile phase (for example in a range between 1 ml / min and 2 ml / min for analytical applications and in a range between 100 ml / min and 200 ml / min for preparative applications) be dimensioned in such a way that a bridging of at least 1 minute is possible. More generally, the buffer volume of the buffer container can be selected, for example, in a range of 1 ml and 1000 ml, in particular in a range of 3 ml and 300 ml.

According to one exemplary embodiment, the buffer container can be designed to reduce its receiving volume when the fluid delivery device is temporarily supplied with mobile phase from the buffer container. Conversely, when temporarily filling up with mobile phase from a (for example refilled or fluidically coupled) mobile phase container, the buffer container can increase its holding volume.

According to one exemplary embodiment, the fluid supply device can have a pretensioning device for pretensioning the buffer container into a pretensioning configuration. For example, the pre-tensioning device can be a mechanical spring for applying a spring pre-tensioning force, one or more magnets for applying a magnetic pre-tensioning force or a defined mass for applying a weight pre-tensioning force. By means of such a pretensioning device, the system can be brought into a well-defined rest configuration.

According to one embodiment, at least one of the at least one mobile phase container can be arranged with an outflow opening directed upwards (cf. for example 8th ). In such a configuration, a fluid line can be immersed in mobile phase in the interior of the mobile phase container in order to provide mobile phase for supplying the fluid delivery device. To replace a mobile phase container, a valve in the fluid line can be closed in the meantime.

According to another exemplary embodiment, at least one of the at least one mobile phase container can be arranged with a downwardly directed outflow opening (see for example 7th ). In such a configuration, the mobile phase container can be inserted upside down in a receiving station, whereby a fluid connection to the fluid conveying device can be established. If a user pulls the mobile phase container (for example when it is emptied) out of the receiving station, a fluid valve in the receiving station can automatically close in order to prevent air bubbles from being drawn into the sample separation device.

According to one exemplary embodiment, the fluid supply device can have a fluid valve which is arranged at a fluid inlet of the buffer container and can be designed to be movable with a movement of the buffer container. For example, such a fluid valve can be rigidly coupled to a movable wall of the buffer container, so that a movement of the wall leads to a movement of a valve body of the fluid valve. Said wall can, for example, be moved in one direction or in another opposite direction, depending on the pressure conditions inside the buffer container, and can thereby take the fluid valve with it. For example, the coupling between the fluid valve and the buffer container can be such that, in the event of excessive pressure in the buffer container, the fluid valve closes a fluid connection between the mobile phase container and the buffer container, thereby protecting pressure-sensitive components of the sample separator downstream of the buffer container from excess pressure. While the fluid valve remains closed, the buffer container serves to continue to supply the fluid delivery device with mobile phase. If the overpressure in the buffer container has decreased, the flexible buffer container can move back and thereby take the fluid valve with it in such a way that a fluid supply of the fluid delivery device is again made possible by means of the mobile phase container. The buffer tank, together with the fluid valve that is strongly coupled to it, thus also serves as a pressure reducer.

According to one embodiment, the bridging mechanism can be designed for, in particular automatic or controlled, return transfer to supply the fluid delivery device with mobile phase from at least one mobile phase container when a temporarily interrupted supply of the fluid delivery device with mobile phase from the at least one mobile phase container is restored. The bridging of the mobile phase supply of the fluid delivery device from the at least one mobile phase container can thus be of a temporary nature. For example, after an emptied mobile phase container has been replaced or refilled, it can be sensed (for example by pressure detection) that the mobile phase container is available again for the mobile phase supply, which can trigger the return of the fluid supply device to an operating mode with the provision of mobile phase from the mobile phase container . Alternatively, the return can be carried out by a user, for example by actuating a button after the replacement of a mobile phase container has been completed.

According to one embodiment, the fluid supply device can have a refilling mechanism for, in particular automatic or controlled, refilling of the buffer container with mobile phase when a temporarily interrupted supply of the fluid delivery device with mobile phase from the at least one mobile phase container is restored. The completely or partially emptied buffer container can be refilled after the mobile phase supply has been restored by a mobile phase container during regular operation, i.e. while the fluid delivery device is being supplied with mobile phase. This makes it possible to ensure that the buffer container is again available for bridging the mobile phase supply after another temporary interruption of the fluid supply from the mobile phase container. In this way, a continuously functioning fluid supply device can be created.

According to one exemplary embodiment, the fluid supply device can have a membrane in the buffer container which divides the buffer container into a variable partial volume that carries mobile phases and a variable partial volume that does not carry mobile phases. Such a membrane can, for example, be designed to be movable, in particular flexible or elastic, so that the size of the two partial volumes can be adjusted or controlled by the application of force. This allows an application-specific or user-specific configuration of the buffer container.

According to one embodiment, the fluid supply device can have a pressure setting device which is designed to act in a pressure setting on the membrane and a fluid valve arranged at a fluid inlet of the buffer container. For example, such a pressure setting device can be formed by a rotatable handpiece which can act (for example by means of a pretensioning device) on the membrane and preferably also on a fluid valve that allows a fluid connection of the buffer container to a mobile phase container to be set depending on an actuation position of the handpiece, in particular allows or prevents.

According to one embodiment, the fluid supply device can have an active setting device for actively setting a receiving volume of the buffer container. For example, a user or a control device can set a position or a movement of a piston in a piston chamber of the buffer container in a user-defined or application-related manner. This enables flexible adjustment of the fluid supply device in accordance with the requirements of a particular application.

According to one embodiment, the fluid supply device can have an air bubble discharge device for discharging an air bubble from the buffer container away from the fluid delivery device. Under unfavorable operating conditions, an undesired air bubble can penetrate the buffer tank. In order to prevent such an air bubble from being transported further into the fluid delivery device, an air bubble discharge device can be integrated into the buffer container. For example, by means of such an air bubble discharge device, an air bubble above a column of liquid in the buffer container can be discharged from the liquid supply device through an upper wall of the buffer container. This can be done, for example, by appropriate user intervention or by mounting a mobile phase container on or above the buffer container, with the pressure conditions inside the buffer container being changed when the mobile phase container is removed so that any air bubble escapes to the outside from the buffer container. Such a venting mechanism can prevent undesired air bubbles in the interior of the sample separation device.

According to one embodiment, the fluid supply device can have two split and recombined parallel flow paths between the at least one mobile phase container and the fluid delivery device, the buffer container being arranged on or in one of the flow paths. For example, one of these flow paths can be used for the regular mobile phase supply mode in order to convey mobile phase from at least one mobile phase container to the fluid conveying device, while the buffer container can be temporarily inactive. The other flow path can be used for a mobile phase bridging mode to convey mobile phase from the buffer vessel to the fluid conveyor.

According to one embodiment, the fluid supply device can have at least one control valve in at least one of the flow paths for controlling whether mobile phase flows through one flow path or through the other flow path. A control valve can preferably be implemented in the flow path for the regular mobile phase supply mode, whereas two control valves can be included in the other flow path for the mobile phase bridging mode in order to accomplish both emptying of mobile phase from the buffer container and filling of the buffer container with mobile phase.

According to an exemplary embodiment, the fluid supply device can have a ventilation device for ventilating the at least one mobile phase container, the ventilation device having a ventilation line between an overpressure source (for example a separate overpressure source for providing air or another gas under overpressure, or an overpressure source already present in a sample separation device, for example the exhaust air of a degasser) and the at least one mobile phase container as well as a ventilation valve which opens or closes the ventilation line and which is designed to be movable with a movement of the buffer container. In particular, if the at least one mobile phase container filled with mobile phase is mounted upside down on a receiving station and is gradually emptied during operation, a negative pressure can develop in the interior of the mobile phase container, which can make subsequent supply of the fluid delivery device with mobile phase difficult or imprecise. In order to avoid the development of an excessive negative pressure in the mobile phase container, a ventilation bypass can be placed between the mobile phase container and a pressure source (particularly preferably realized by exhaust air from a degasser, which is often provided in a sample separator anyway), which is controlled by the ventilation valve through the pressure in the buffer container can be controlled. Depending on the pressure conditions in the buffer tank, the ventilation valve opens or closes the ventilation line.

The sample separation device can be a microfluidic measuring device, a life science device, a liquid chromatography device, an HPLC (High Performance Liquid Chromatography), a UHPLC system, an SFC (supercritical liquid chromatography) device, a gas chromatography device or a gel electrophoresis device. However, many other uses are possible.

The fluid drive device or the fluid pump can be set up, for example, to convey the mobile phase through the system at a high pressure, for example a few 100 bar up to 1000 bar and more.

The sample separation device can have a sample injector or a sample application unit for introducing the sample into the fluidic separation path. Such a sample injector can have an injection needle that can be coupled to a seat in a corresponding liquid path, wherein the needle can be moved out of this seat in order to take up the sample. After the needle has been reinserted into the seat, the sample can be processed further.

The sample separation device can have a fraction collector for collecting the separated components. Such a faction collector can lead the different components into different liquid containers, for example. The analyzed sample can also be fed to a drainage container or waste container.

The sample separation device can preferably have a detector for detecting the separated sample. Such a detector can generate a signal which can be observed and / or recorded and which is indicative of the presence and amount of sample fractions in the medium flowing through the system.

Figure list

• 1 zeigt Details eines HPLC-Systems zum Trennen einer fluidischen Probe gemäß einem exemplarischen Ausführungsbeispiel der Erfindung.
• 2 zeigt eine Fluidversorgungsvorrichtung gemäß einem exemplarischen Ausführungsbeispiel der Erfindung.
• 3 zeigt eine Fluidversorgungsvorrichtung gemäß einem anderen exemplarischen Ausführungsbeispiel der Erfindung.
• 4 zeigt eine Fluidversorgungsvorrichtung gemäß noch einem anderen exemplarischen Ausführungsbeispiel der Erfindung.
• 5 zeigt eine Fluidversorgungsvorrichtung gemäß einem weiteren exemplarischen Ausführungsbeispiel der Erfindung.
• 6 zeigt eine Fluidversorgungsvorrichtung gemäß noch einem anderen exemplarischen Ausführungsbeispiel der Erfindung.
• 7 zeigt einen Mobilphasenbehälter einer Fluidversorgungsvorrichtung gemäß einem exemplarischen Ausführungsbeispiel der Erfindung.
• 8 zeigt einen anderen Mobilphasenbehälter einer Fluidversorgungsvorrichtung gemäß einem exemplarischen Ausführungsbeispiel der Erfindung.
• 9 und 10 zeigen zwei Ansichten eines Pufferbehälters mit veränderlicher Form einer Fluidversorgungsvorrichtung gemäß einem exemplarischen Ausführungsbeispiel der Erfindung.
• 11 und 12 zeigen zwei Ansichten eines Pufferbehälters aus einem elastischen Material einer Fluidversorgungsvorrichtung gemäß einem anderen exemplarischen Ausführungsbeispiel der Erfindung.
• 13 und 14 zeigen zwei Ansichten eines Pufferbehälters mit einen zum Verändern des Aufnahmevolumens des Pufferbehälters bewegbaren Körper einer Fluidversorgungsvorrichtung gemäß noch einem anderen exemplarischen Ausführungsbeispiel der Erfindung.

Other objects and many of the accompanying advantages of embodiments of the present invention will become readily apparent and better understood with reference to the following more detailed description of embodiments in conjunction with the accompanying drawings. Features that are essentially or functionally identical or similar are provided with the same reference symbols.

• 1 shows details of an HPLC system for separating a fluidic sample according to an exemplary embodiment of the invention.
• 2 shows a fluid supply device according to an exemplary embodiment of the invention.
• 3 shows a fluid supply device according to another exemplary embodiment of the invention.
• 4th shows a fluid supply device according to yet another exemplary embodiment of the invention.
• 5 shows a fluid supply device according to a further exemplary embodiment of the invention.
• 6th shows a fluid supply device according to yet another exemplary embodiment of the invention.
• 7th shows a mobile phase container of a fluid supply device according to an exemplary embodiment of the invention.
• 8th shows another mobile phase container of a fluid supply device according to an exemplary embodiment of the invention.
• 9 and 10 show two views of a buffer container with variable shape of a fluid supply device according to an exemplary embodiment of the invention.
• 11 and 12th show two views of a buffer container made of an elastic material of a fluid supply device according to another exemplary embodiment of the invention.
• 13th and 14th show two views of a buffer container with a body of a fluid supply device that can be moved to change the receiving volume of the buffer container according to yet another exemplary embodiment of the invention.

The representation in the drawing is schematic.

Before exemplary exemplary embodiments of the invention are described in more detail with reference to the figures, some fundamental considerations of the present invention, on the basis of which exemplary embodiments of the invention have been developed, are to be described in general.

Conventionally, a solvent bottle in a sample separation device can supply a pump with mobile phase during separation operation. Refilling or replacing such a solvent bottle may be necessary during operation if the remaining filling level with solvent is too low for a current separation run to be carried out regularly to its end. In order not to interrupt ongoing operation, the bottle cap can be lifted slightly to refill and solvent can be added from another solvent container. It can happen in an undesirable manner that, for example, aggressive solvents are spilled. When a bottle is exchanged by lifting a filter and a solvent line connected to it from a bottle and then placing and subsequently fluidically coupling the solvent line to another bottle, the filter and solvent line are briefly not covered with liquid, which means that air bubbles which influence a separation result are undesirable in the fluidic system of the sample separation device can get. The conventional concepts described for replacing a mobile phase container while a sample separation device is in operation are therefore prone to errors and risky, since safety standards may not be met (for example, with regard to working at overhead height, leaking solvent, etc.) and / or a considerable amount of air bubbles in a sample separator can penetrate.

According to an exemplary embodiment of the invention, in a fluid supply device, a buffer or storage container can be located within a flow path between Mobile phase or solvent container on the one hand and a fluid delivery device (in particular a pump) on the other hand, the solvent supply can be maintained for a certain period of time with the mobile phase-filled buffer container if, for example, the solvent container is emptied and / or it is to be replaced. In such a scenario, an intermediate storage device in the form of the buffer container can advantageously be provided so that a separation run can continue in an associated sample separation device while the mobile phase container is exchanged or refilled. This intermediate store can preferably counteract a negative pressure, for example by reducing the volume. According to an exemplary embodiment of the invention, a flexible buffer volume can be provided between a solvent container and the inlet of the solvent supply pump. When a solvent bottle is coupled, the flexible buffer volume can be filled with solvent so that the contents of the flexible volume can still supply the pump when the solvent bottle has become empty. A reservoir with a suitable volume (of, for example, 5 ml or more) can thus be installed between the solvent container and the pump. The reservoir can preferably be designed as a passive component that can build up an essentially constant negative pressure due to the design during filling and in reserve operation. Clearly, the buffer container can provide an inline solvent reservoir for temporarily bridging an interrupted fluid supply mechanism based on at least one mobile phase container.

According to an exemplary embodiment of the invention, a buffer container can be integrated as a solvent reservoir in a fluid supply device for handling solvents. This buffer container, which serves as a reservoir for the mobile phase, can be filled with an amount of mobile phase (for example a solvent or a solvent composition) in order, for example, to bridge the time required to replace a mobile phase container (for example a solvent bottle) (for example 1 minute). The reservoir can advantageously be able to prevent or inhibit a generation of negative pressure in the solvent lines and the pump of the sample separation device. After the mobile phase container has been replaced during the ongoing separation operation, the buffer container can refill itself with new mobile phase from the replaced mobile phase container.

If a solvent bottle is refilled during a separation run of a sample separation device designed, for example, as a liquid chromatography sample separation device, according to an exemplary embodiment of the invention, the solvent is reliably protected from undesired spillage, which improves operational safety compared to conventional systems. Furthermore, according to exemplary embodiments of the invention, when a fluid line with a filter is removed from a mobile phase container to be exchanged, ambient air is inadvertently sucked in, which leads to air bubbles in the solvent line. This can also prevent air from being released in the mobile phase when a mobile phase container is refilled or replaced, which can impair a mobile phase previously degassed in a degasser of the sample separation device. As a result, conventional errors and / or dangerous situations according to exemplary embodiments of the invention can be avoided.

According to an exemplary embodiment of the invention, a user advantageously does not need to worry about the continuous flow of mobile phase, since this task can be carried out automatically by the buffer container. In addition, a fluid supply device according to an exemplary embodiment of the invention is protected against undesired penetration of solvent bubbles into the sample separation device when a mobile phase container is exchanged.

According to an exemplary embodiment, the buffer container designed as a solvent reservoir can for example be made of a flexible material and / or a flexible shape and / or a (for example movable) element that enables the buffer container to change its buffer volume (in particular to shrink after a mobile phase container has been disconnected from the sample separator and will expand after a mobile phase container has been connected to the sample separator).

If a mobile phase container is removed from the sample separation device, it can be advantageous to seal the sample separation device so that no air can get into the solvent line. With a mobile phase container that is connected upside down to the fluid supply device, a device-side mobile phase line can be automatically closed when a mobile phase container is removed. If, on the other hand, the mobile phase container is parked at the bottom and implemented with the fluid outlet open at the top, a valve between an inlet filter on a fluid line and the buffer container can advantageously be closed, before the solvent filter is withdrawn from the mobile phase container. The mobile phase is supplied to the sample separation device when the valve is closed by removing it from the buffer container. After a new mobile phase container has been reconnected to the fluid supply device of the sample separation device, the device-side solvent line can advantageously be reopened (for example automatically or manually). Then the reservoir begins to fill itself in the form of the buffer container. The flow between the pump and the reservoir can advantageously remain constant, whereas the flow between the reservoir and the mobile phase container can increase until the buffer container is filled again.

Since the buffer container can be fluidically coupled to a device-side solvent line, the buffer container can be cleaned when the solvent line is cleaned. This can be done, for example, when changing to a different type of solvent. The dimensioning and design of the buffer tank can be made in such a way that no solvent residues can form.

1. 1. Ein auszutauschender Mobilphasenbehälter kann abgenommen oder getrennt werden, wobei eine instrumentenseitige Lösungsmittelleitung (zum Beispiel durch ein Ventil) geschlossen werden kann.
2. 2. Ein sich ausbildender Negativdruck kann durch ein schrumpfendes Puffervolumen des Pufferbehälters ganz oder teilweise kompensiert werden.
3. 3. Ein neuer oder nachgefüllter Mobilphasenbehälter kann eingesetzt oder wieder angeschlossen werden. Dadurch erweitert sich der Pufferbehälter, und der Durchfluss zwischen Mobilphasenbehälter und Pufferbehälter kann erhöht werden.
4. 4. Der Pufferbehälter kann wieder gefüllt werden, wobei sich der Durchfluss zwischen Mobilphasenbehälter und Pufferbehälter auf den gleichen Durchfluss wie zwischen Pufferbehälter und Fluidfördereinrichtung reduzieren kann.

A working principle of a fluid supply device according to an exemplary embodiment of the invention is described below:

1. 1. A mobile phase container to be exchanged can be removed or separated, whereby a solvent line on the instrument side can be closed (for example by a valve).
2. 2. A negative pressure that develops can be fully or partially compensated for by a shrinking buffer volume of the buffer container.
3. 3. A new or refilled mobile phase container can be inserted or reconnected. This expands the buffer tank and the flow between the mobile phase tank and the buffer tank can be increased.
4. 4. The buffer container can be filled again, whereby the flow between the mobile phase container and the buffer container can be reduced to the same flow rate as between the buffer container and the fluid delivery device.

According to one embodiment, the buffer container can be designed as a bellows and, for example, can be passively controlled. According to another exemplary embodiment, the buffer container can be designed as a cylinder with a piston and an active control based on different system states.

Another exemplary embodiment can be based on a software solution which prompts a user in good time to provide fresh solvent and ensures that a required amount of solvent is available in advance for a respective chromatographic separation run. This can be ensured, for example, by a solvent consumption monitoring and / or by a solvent consumption forecast, which can be done, for example, by continuously weighing the solvent containers.

According to an exemplary embodiment of the invention, a mobile phase container can be connected to a fluid supply device. This allows a buffer tank to fill with mobile phase from the mobile phase tank. In the event of a later exchange of an emptied mobile phase container or to temporarily avoid an undesirably high pressure, the mobile phase in the buffer container can temporarily take over the supply of a fluid delivery device of a sample separation device with mobile phase. This temporary takeover of the mobile phase supply by the buffer container can then be ended when a new mobile phase container is connected to the fluid supply device or when a temporary overpressure has dropped sufficiently. During the bridging of the mobile phase supply by the buffer container, for example, a separation run for separating a fluidic sample in a sample separation device can be continued and regularly ended, even if a mobile phase supply from a mobile phase container is temporarily interrupted. After restoring the fluid supply through a mobile phase container, the buffer container can be filled again with mobile phase from the mobile phase container. The procedure can be repeated continuously.

1 shows the basic structure of an HPLC system as a sample separation device 10 as it can be used for liquid chromatography, for example. A fluid conveyor 20th using solvents from a fluid supply facility 100 is supplied, drives a mobile phase through a sample separator 30th (such as a chromatographic column) that includes a stationary phase. A degasser 27 can degas the solvent before it reaches the fluid delivery device 20th are fed. A sample application unit 40 (also referred to as an injector) is between the fluid delivery device 20th and the sample separator 30th arranged to introduce a sample liquid into the fluidic separation path. The stationary phase of the sample separator 30th is intended to separate components of the fluidic sample. One detector 50 , for example a flow cell, detects separated components of the sample, and a fractionation device 60 can be provided to dispense separated components of the sample into containers provided for this purpose. The liquids can after passing the detector 50 into a drain tank (not shown) or the fractionation device 60 are issued.

While a fluid path between the fluid delivery device 20th and the sample separator 30th is typically under high pressure, the sample liquid is initially under normal pressure in an area separated from the liquid path, a so-called sample loop, of the sample application unit 40 entered, which in turn brings the sample liquid into the high pressure liquid path. During the connection of the sample liquid, which is initially under normal pressure, in the sample loop to the high pressure liquid path, the contents of the sample loop are brought to the system pressure of the sample separation device designed as HPLC 10 brought. A control unit 70 controls the individual components 20th , 27 , 30th , 40 , 50 , 60 of the sample separator 10 , and optionally also the fluid supply device 100 .

The fluid supply device already mentioned 100 serves to supply the fluid delivery device 20th with a mobile phase. The mobile phase can be a solvent or a mixture of two or more solvent components and can consist of one or more mobile phase containers designed, for example, as solvent containers 102 are formed. Said fluid supply device 100 has a buffer tank 104 for storing a buffer amount of mobile phase in a fluidic path between the mobile phase containers 102 and the fluid delivery device 20th on. The fluid supply device also contains 100 a bridging mechanism 106 , the temporary supply of the fluid conveying device 20th with mobile phase from the buffer tank 104 accomplished, for example, when the supply of the fluid delivery device 20th with mobile phase from the mobile phase containers 102 is temporarily interrupted. Such an interruption can occur, for example, when a mobile phase container 102 has been emptied and replaced. During the exchange, the supply of mobile phase to the fluid conveyor is stopped 20th from the buffer tank 104 continued uninterrupted. An interruption in the supply of the fluid delivery device 20th with solvents from the mobile phase containers 102 but can also occur if, in order to avoid pressure peaks, at least one of the mobile phase containers 102 temporarily fluidically from the buffer tank 104 and therefore from the fluid delivery device 20th is disconnected. Before and after an interim supply of the fluid delivery device 20th with mobile phase from the buffer tank 104 can the buffer tank 104 at least partially with mobile phase from the mobile phase containers 102 be filled or refilled in order to be prepared for temporary provision of the mobile phase in the event of an interruption.

In the following, reference will be made to 2 until 6th Exemplary embodiments of fluid supply devices 100 described in the sample separator 10 according to 1 can be implemented. 7th and 8th show exemplary configurations of mobile phase containers 102 , which are part of a respective fluid supply device 100 can form. 9 until 14th show exemplary embodiments of buffer containers 104 .

2 shows a fluid supply device 100 according to an exemplary embodiment of the invention. 3 shows a fluid supply device 100 according to another exemplary embodiment of the invention.

The illustrated fluid supply device 100 serves to supply an in 1 fluid delivery device described in more detail 20th a sample separator 10 with a mobile phase from a mobile phase container 102 . Such a mobile phase container 102 is in 2 not shown, but can, for example, on a fixed mounting platform 150 be put on. More precisely, the mobile phase container 102 with his weight on the receiving platform 150 act what when putting on the mobile phase container 102 to a limited movement of the receiving platform 150 downwards or when removing the mobile phase container 102 to a limited movement of the receiving platform 150 can lead to the top. Furthermore, the fluid supply device 100 a buffer container designed here as a bellows 104 for storing or taking up a certain maximum buffer amount of mobile phase. Said flexible bellows provides a spring function. The buffer tank 104 is in a fluidic path between the mobile phase container 102 and the fluid delivery device 20th arranged, whereby optionally one or more further components can be arranged in this path (for example a degasser 27 , compare 1 ).

Furthermore, the fluid supply device 100 a bridging mechanism 106 for the temporary supply of the fluid delivery device 20th with mobile phase from the buffer tank 104 on. The bridging mechanism 106 ensures that in the event of a temporary interruption of the mobile phase supply by the mobile phase container (s) 102 the mobile phase supply of the fluid delivery device 20th does not collapse, but using mobile phase in the buffer tank 104 is maintained uninterrupted. This can result in both undesirable interference with an ongoing sample separation run for separating a fluidic sample using mobile phase and the penetration of undesired air bubbles into the sample separation device 10 be avoided.

In particular is the lock-up mechanism 106 according to 2 for the temporary supply of the fluid delivery device 20th with mobile phase from the buffer tank 104 formed when a supply of the fluid delivery device 20th with mobile phase from the at least one mobile phase container 102 is temporarily interrupted. This can be the case, for example, while a user has an emptied mobile phase container 102 exchanges or refills. During this time, an already running sample separation run with mobile phase can be removed from the buffer container 104 be continued until a mobile phase container filled with mobile phase again 102 is available.

Alternatively or in addition, the bridging mechanism 106 also for the temporary supply of the fluid delivery device 20th with mobile phase from the buffer tank 104 be designed to one of the mobile phase container 102 relieve excessive pressure caused. Such excessive pressure, for example from a heavily filled mobile phase container 102 can be generated, components can be downstream of the buffer tank 104 affect or even harm. In order to avoid such impairment or damage, a fluid connection between a mobile phase container responsible for the excessive pressure can be used 102 on the one hand and the buffer tank 104 and the fluid delivery device 20th on the other hand are temporarily interrupted. The buffer tank takes over during this bridging period 104 temporarily the mobile phase supply of the fluid delivery device 20th until the excessive pressure in the buffer tank 104 has degraded.

To provide the functionality described above, the buffer container 104 have a flexibly changeable receiving volume. In particular, the buffer container 104 have a variable bellows shape. The buffer container can be advantageous 104 be formed due to its bellows shape when temporarily supplying the fluid delivery device 20th with mobile phase from the buffer tank 104 its receiving volume with delivery of mobile phase to the fluid delivery device 20th to reduce.

In an expanded configuration of the buffer container designed as a bellows 104 can the buffer tank 104 contain a maximum buffer amount of mobile phase, which at a given flow rate for at least 1 minute to bridge an interrupted mobile phase supply from the at least one mobile phase container 102 enables. For one (e.g. for analytical applications of the sample separator 10 typical) flow rate in a range from 1 ml / min to 2 ml / min can be the maximum internal volume of the buffer container 104 for example at least 2 ml, preferably at least 5 ml. In one (for example, for preparative applications of the sample separation device 10 typical) flow rate in a range from 100 ml / min to 200 ml / min can be the maximum internal volume of the buffer container 104 for example at least 200 ml, preferably at least 500 ml.

The fluid supply device advantageously has 100 a fluid valve 114 on that at a fluid inlet of the buffer tank 104 is arranged and with a movement of the buffer container 104 is designed to be movable. Like a double arrow 152 in 2 is shown, a bottom wall 156 of the buffer tank 104 if the volume of the buffer tank changes due to pressure 104 in flow direction 154 of the mobile phase are moved downwards, or in the opposite direction. The rigid on the axially movable bottom wall 156 attached fluid valve 114 moves with the bottom wall 156 with and is closed with a downward movement and opened with an upward movement.

After completion of the interim mobile phase supply of the fluid delivery device 20th with mobile phase from the buffer tank 104 and after fluidic reconnection of the mobile phase container 102 can the bypass mechanism 106 for automatic transfer back to supply the fluid delivery device 20th with mobile phase from the mobile phase container 102 be trained. This is achieved through the interaction of the fluid valve 114 and the buffer tank 104 accomplished as described below. The fluid valve also function 114 and the buffer tank 104 also as a replenishment mechanism 116 for automatic refilling of the buffer tank 104 with mobile phase from a mobile phase container 102 after a temporarily interrupted supply of the fluid delivery device 20th with mobile phase from a mobile phase container 102 is restored. You can also use the buffer tank 104 an air bubble discharge device due to its configuration described in more detail below 140 for evacuating an air bubble from the buffer container 104 away from the fluid conveyor 20th to be provided.

For example, according to 2 a mobile phase container 102 on the receiving platform 150 be mounted, for example upside down according to 7th . This configuration can, especially when the mobile phase container is completely full 102 , lead to high pressurization of downstream components. The configuration of the buffer tank shown here is used in such a scenario 104 with fluid valve 114 As a pressure regulator or pressure reducer, which avoids excessive pressure on downstream components. In the event of excessive tank pressure, the mobile phase tank 102 with the mobile phase contained therein on the buffer container 104 can exercise, an expansion or expansion of the buffer tank takes place 104 , whereby its bottom wall 156 moved down. This makes it rigid at the bottom wall 156 attached fluid valve 114 pulled down and closes in a valve seat. The mobile phase supply of the fluid delivery device 20th is then temporarily removed from the buffer tank 104 taken over, which is still filled with mobile phase. Is the mobile phase from the buffer tank 104 in such a proportion to the fluid delivery device 20th been conveyed that the internal pressure in the buffer tank 104 smaller than a spring preload force of the buffer container designed as a bellows 104 the fluid valve opens 114 again, and new mobile phase arrives from the at least one mobile phase container 102 into the buffer tank 104 and from there to the fluid delivery device 20th . The buffer tank 104 is again filled with the mobile phase, and the conveying operation of the fluid conveying device 20th can be maintained continuously. The mechanism described can be repeated whenever the mobile phase container 102 conditional pressure in the buffer tank 104 one through the design of the buffer tank 104 and the fluid valve 114 exceeds a predetermined threshold.

Even when replacing an emptied mobile phase container 102 can the buffer tank 104 for an uninterrupted supply of the fluid conveying device 20th care with mobile phase. Would a user want such a mobile phase container 102 can be exchanged by closing an in 7th and 8th locking device shown and described in more detail below 134 initially advantageously avoided that the fluid delivery device 20th during the exchange of a mobile phase container 102 a considerable amount of ambient air in the fluidic system of the sample separation device 10 soaks in. In the buffer tank 104 mobile phase still contained is then released by the fluid delivery device 20th sucked in and conveyed, whereby the supply of the sample separator 10 is maintained with the mobile phase. Will be used after the mobile phase container has been replaced 102 the closing device 134 opened again, the supply of the fluid delivery device is 20th with mobile phase from the exchanged mobile phase container 102 continued continuously and without interruption. This also fills the buffer tank 104 again with the mobile phase from the exchanged mobile phase container 102 .

In the 2 illustrated fluid supply device 100 also provides an air bubble discharge device 140 ready. As already described, a mobile phase container 102 with his weight on the platform 150 be put on and can push this down. When removing a mobile phase container 102 (for example in the course of an exchange) the recording platform 150 move up a little again. This becomes the fluid valve 114 reliably closed, and air bubbles can be rinsed out via an upper side of the buffer container 104 by means of an appropriate ventilation mechanism (e.g. air holes or flaps on the top). This can also be done manually by a user.

If, for example, a mobile phase container designed as a solvent bottle 102 is closed, the vapor pressure is equalized in a free space. This leads to increased pressure inside. This process speeds up when the bottle is turned or shaken. The fluid delivery device designed, for example, as a liquid chromatography pump 20th can be affected by this change in pressure. The configuration according to 2 allows pressure control to avoid such impairment. The buffer container designed as a bellows 104 expands downwards with increased pressure. This becomes the fluid valve 114 on the mobile phase container acting as a pressure bottle 102 closed. When the fluid conveyor 20th If the mobile phase continues, the bellows and the fluid valve shrink 114 is opened again when the pressure reaches a certain lower threshold value. The threshold pressure is determined by the elasticity of the bellows, a spring, a magnet (cf. 3 ) or another pretensioning device 110 Are defined.

To get air bubbles out of the bellows, you can move in the direction of an arrow 160 be applied. This can happen automatically when a new mobile phase container 102 is installed, especially on the mounting platform 150 is put on.

The fluid supply device 100 according to 3 differs from the fluid supply device 100 according to 2 in that according to 3 as a pretensioning device 110 a first set of magnets 162 on the bottom wall 156 of the buffer tank 104 and a second set of magnets 164 on a reference floor 166 are appropriate. the Magnets 162 , 164 are configured to repel each other so that the magnetic pretensioner 110 the buffer tank 104 biased into a contracted configuration.

4th shows a fluid supply device 100 according to yet another exemplary embodiment of the invention.

In the 4th illustrated fluid supply device 100 has an elastic membrane 118 in the buffer tank 104 on that the buffer tank 104 into a variable partial volume leading to the mobile phase 120 and into a variable, non-mobile phase leading partial volume 122 divides. For example, the membrane 118 be made of rubber or silicone. The elastic membrane is clearly used 118 according to 4th as a spring element and represents a functional counterpart to the bellows according to 2 and 3 is. Furthermore, according to 4th a pressure adjusting device 124 provided for the pressure-adjusting action on the membrane 118 and one at a fluid inlet of the buffer container 104 arranged fluid valve 114 is trained. By means of the pressure adjustment device 124 a user can set a storage volume of the buffer container 104 , a switching state of the fluid valve 114 and thus an operating point of the fluid supply device 100 to adjust. By operating the pressure setting device 124 an operating point can thus be set at which the system stabilizes. In particular, a working pressure can be set at which the fluid valve 114 opens or closes. The fluid valve 114 can be designed as a valve with a spring that controls the fluid valve 114 biased upwards.

5 shows a fluid supply device 100 according to a further exemplary embodiment of the invention.

The fluid supply device 100 according to 5 differs from the fluid supply device 100 according to 2 in that according to 5 additionally a ventilation device 136 to ventilate the mobile phase container 102 is provided. Said ventilation device 136 has a ventilation duct 138 between an overpressure source and the mobile phase container to be ventilated 102 as well as a vent line 138 opening or closing ventilation valve 139 on that on a valve seat in the ventilation line 138 can act. The ventilation valve 139 is with one movement of the buffer tank 104 designed to be movable. More precisely, it is the ventilation valve 139 with a movable bottom wall 156 of the buffer tank 104 rigidly coupled. The ventilation line clearly forms 138 a pressure line in a for example according to 7th mobile phase container configured upside down 102 . If from an upside-down mobile phase container 102 mobile phase flows off, can be in the mobile phase container 102 form a negative pressure, the further provision of mobile phase from the mobile phase container 102 inhibits. To ensure trouble-free provision of a mobile phase from the mobile phase container 102 such a negative pressure can be ensured by ventilation through the ventilation line 138 be balanced. To provide such ventilation is the vent valve 139 that is the ventilation duct 138 selectively opens or closes, rigid on the bottom wall 156 of the buffer tank 104 attached and moves with the bottom wall during operation 156 with. Opens the ventilation valve 139 with a corresponding movement of the bottom wall 156 of the buffer tank 104 , air is drawn from a pressure reservoir through the ventilation line 138 into the mobile phase container 102 directed (see arrows 168 ). It is particularly advantageous for this purpose that the mobile phase container 102 remote end of the ventilation line 138 with an exhaust air connection of the degasser 27 to couple so that exhaust air from the degasser 27 without additional effort to vent the mobile phase container 102 can be used. The mechanism described thus serves to ventilate an upside-down solvent bottle. In the 5 The configuration shown thus enables air to be supplied (preferably under a slight excess pressure of, for example, 50 mbar) to ventilate a mobile phase container 102 , for which exhaust air from the degasser is preferred 27 can be used.

6th shows a fluid supply device 100 according to yet another exemplary embodiment of the invention.

When configured according to 6th are two on a splitter 170 split up and at a unification facility 172 re-merged parallel river paths 128 , 130 between the mobile phase container 102 and the fluid delivery device 20th arranged. The one here as a piston chamber with a controllable piston as a movable body 108 trained buffer tank 104 is on the river path 130 fluidly connected, more precisely to one of the flow path 130 branching arm in fluid communication with mobile phase in the flow path 130 . A function block 174 walking the river path 128 contains is in normal operation of the fluid supply device 100 activated in which the mobile phase container 102 the fluid delivery device 20th supplied with mobile phase. Another function block 176 walking the river path 130 contains, serves as a buffer reservoir for the temporary provision of mobile phase during an exchange of a mobile phase container 102 as well as for pressure regulation.

The fluid supply device 100 according to 6th has a first control valve 131 and a second control valve 132 on that in the river path 130 are arranged. A third control valve 133 is in the river path 128 arranged. By switching the control valves accordingly 131-133 can be controlled whether mobile phase through the one flow path 128 or through the other river path 130 flows. Are the first control valve 131 and the second control valve 132 closed and is the third control valve 133 open, mobile phase flows from the mobile phase container during normal operation 102 through the river path 128 to the fluid conveyor 20th . Are the third control valve 133 and the first control valve 131 closed and is the second control valve 132 open, mobile phase flows from the buffer tank in bridging mode 104 through the lower part of the river path 130 to the fluid conveyor 20th . Are the third control valve 133 and the second control valve 132 closed and is the first control valve 131 open, mobile phase flows from the mobile phase container in the refill operation 102 through the upper part of the river path 130 into the buffer tank 104 .

According to 6th is an actively controlled reservoir of mobile phase in the form of the buffer tank 104 provided, in which to change the receiving volume of the buffer container 104 a movable body designed as a piston 108 in the buffer tank 104 is arranged displaceably.

The principle of operation of the fluid supply device 100 according to 6th is as follows: The mobile phase container 102 can be designed as a bottle with a unidirectional air inlet valve that opens when the pressure P1 in the mobile phase container 102 below ambient pressure P0 falls. Here, P1 can be lower, equal to or higher than P0. Furthermore, the plurality of control valves 131-133 installed, which are actively controlled depending on the different system conditions.

When a new mobile phase container 102 is installed and with its orifice 112 is oriented downwards (for example as in 7th shown), the overpressure in the mobile phase container 102 by filling the empty buffer tank 104 reduced. Here are the third control valve 133 and the second control valve 132 closed and is the first control valve 131 opened. If now there is an overpressure in the mobile phase container 102 is present, the movable body designed as a piston can 108 in the buffer tank 104 actively moved to mobile phase from the mobile phase container 102 into the buffer tank 104 to pull.

This operating mode can be carried out until there is no longer any excess pressure in the mobile phase container 102 is available. Then the fluid delivery device, designed for example as a pump, can 20th mobile phase directly from the mobile phase container 102 draw. Here are the first control valve 131 and the second control valve 132 closed and is the third control valve 133 opened.

When the mobile phase container 102 during ongoing operation (for example during a separation run to separate a fluidic sample in the sample separation device 10 using by means of the fluid delivery device 20th conveyed mobile phase) is removed, mobile phase is removed from the buffer tank 104 taken. Here are the third control valve 133 and the first control valve 131 closed and is the second control valve 132 opened.

7th shows a mobile phase container 102 a fluid supply device 100 according to an exemplary embodiment of the invention. The illustrated mobile phase container 102 is with the orifice pointing downwards 112 arranged and is in a receiving station 180 arranged. When the mobile phase container 102 with outflow opening pointing downwards 112 mechanically at the receiving station 180 is included, is also a fluidic coupling via a fluid line 178 with an in 7th buffer container not shown 104 enables.

7th also shows that a locking device 134 in the admission ward 180 can be integrated. The closing device 134 is for the preferably automatic closing of a fluid connection by means of the fluid line 178 between the mobile phase container 102 and the (in 7th not shown) buffer tank 104 educated. It can preferably be used during fluidic separation of the mobile phase container 102 from the receiving station 180 and thus from the fluid supply device 100 the closing device 134 the fluid line 178 Seal until a full or new mobile phase container 108 at the receiving station 180 is recorded. The closing device 134 according to 7th can be designed as a self-closing valve that when pulling out the mobile phase container 102 is automatically transferred to a closed state.

8th shows another mobile phase container 102 a fluid supply device 100 according to an exemplary embodiment of the invention. According to 8th is a mobile phase container 102 with upward directed discharge opening 112 arranged and stands with a container bottom 182 on an underground. A fluid line 178 is through a lid 184 of the mobile phase container 102 passed through and immersed in mobile phase inside the mobile phase container 102 a. At the end of the fluid line 178 can be a filter 186 to the Filtering out of particles and the like from the mobile phase can be provided from the mobile phase container 102 towards an in 8th fluid delivery device, not shown 20th should be promoted.

The in 8th Mobile phase container shown 102 is with a locking device 134 fluidically coupled, according to 8th in the fluid line 178 is arranged. The closing device designed as a valve to be operated by a user 134 is used for user-defined selective closing of a fluid connection between the mobile phase container 102 and one in 8th buffer container not shown 104 . Before the fluidic separation of the mobile phase container, a user can 102 from the fluid supply device 100 the closing device designed as a valve 134 seal fluid-tight and can thereby prevent air bubbles or the like from entering the sample separation device 10 get in.

The closing device 134 according to 8th can be designed as a passive valve that can be actuated by a user for switching. By closing this valve before changing the bottle, an ingress of an air bubble into the system can be avoided.

Alternatively, the closing device 134 from the sample separator 10 or the fluid supply device 100 be actively controllable. For example, the filling level in the mobile phase container 102 be measured. If this falls below a critical value, a user can be alerted accordingly. A user can then press an operating button to lock the locking device 134 trigger. Alternatively, the system can also carry out the locking process automatically.

9 until 14th show examples of different possible reservoir concepts:

9 and 10 show two views of a buffer tank 104 with variable shape according to an exemplary embodiment of the invention. According to 9 and 10 has the buffer tank 104 a variable bellows shape with spring properties.

11 and 12th show two views of a buffer tank 104 made of an elastic material (such as rubber) according to another exemplary embodiment of the invention. The elasticity of the material of the wall of the buffer container 104 provides spring properties.

13th and 14th show two views of a buffer tank 104 with one for changing the volume of the buffer tank 104 movable body 108 according to another exemplary embodiment of the invention.

By moving the body 108 in the buffer tank 104 its recording volume can be changed. The movable body, designed here as a disk or plate 108 is attached to the end of a coil spring, which acts as a biasing device 110 for pre-tensioning the buffer tank 104 is formed into a bias configuration.

The buffer containers each having a spring function 104 according to 9 until 14th can be configured in such a way that a spring constant suitable for an application is achieved. Clearly, the spring force should not be greater than the tensile force of the fluid delivery device 20th . In addition, the spring force should be such that after a mobile phase container has been replaced 102 and after provision of the mobile phase from the buffer tank 104 the interior of which is then filled up again with a new mobile phase.

It should be noted that the term “having” does not exclude other elements, and that the “a” does not preclude a plurality. Elements that are described in connection with different exemplary embodiments can also be combined. It should also be noted that any reference signs in the claims should not be construed as limiting the scope of the claims.

QUOTES INCLUDED IN THE DESCRIPTION

This list of the documents listed by the applicant was generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Patent literature cited

• EP 0309596 B1 [0002]

Claims (20)

Fluid supply device (100) for supplying a fluid delivery device (20) of a sample separation device (10) with a mobile phase from at least one mobile phase container (102), the fluid supply device (100) having: a buffer container (104) for storing a buffer amount of mobile phase in or on a fluidic path between the at least one mobile phase container (102) and the fluid delivery device (20); and a bridging mechanism (106) for temporarily supplying the fluid delivery device (20) with mobile phase from the buffer container (104) when the at least one mobile phase container (102) is temporarily decoupled from the provision of mobile phase. Fluid supply device (100) according to Claim 1 , having at least one of the following features: wherein the bridging mechanism (106) is designed to temporarily supply the fluid delivery device (20) with mobile phase from the buffer container (104) when the fluid delivery device (20) is supplied with mobile phase from the at least one mobile phase container (102) is temporarily interrupted during an exchange of the at least one mobile phase container (102); wherein the bridging mechanism (106) is designed for temporarily supplying the fluid conveying device (20) with mobile phase from the buffer container (104) in order to reduce an excessive pressure caused by the at least one mobile phase container (102). Fluid supply device (100) according to Claim 1 or 2 , having a closing device (134) which is designed for, in particular automatic or user-defined, closing of a fluid connection between the at least one mobile phase container (102) and the buffer container (104), in particular when the at least one mobile phase container (102) is fluidically separated from the Fluid supply device (100). Fluid supply device (100) according to one of the Claims 1 until 3 , wherein the buffer container (104) has a flexibly changeable receiving volume. Fluid supply device (100) according to one of the Claims 1 until 4th , having at least one of the following features: wherein the buffer container (104) comprises or consists of an elastic material; wherein the buffer container (104) has a variable shape, in particular a bellows shape; having a body (108) which can be moved to change the receiving volume of the buffer container (104), in particular a movable piston or a movable membrane, in the buffer container (104). Fluid supply device (100) according to one of the Claims 1 until 5 , wherein the buffer container (104) is designed to store a maximum amount of buffer of mobile phase of at least 1 ml, in particular of at least 3 ml, further in particular of at least 5 ml. Fluid supply device (100) according to one of the Claims 1 until 6th wherein the buffer container (104) is designed to reduce its receiving volume when the fluid delivery device (20) is temporarily supplied with mobile phase from the buffer container (104). Fluid supply device (100) according to one of the Claims 1 until 7th , comprising a biasing device (110) for biasing the buffer container (104) into a biasing configuration. Fluid supply device (100) according to one of the Claims 1 until 8th , having at least one of the following features: wherein the fluid supply device (100) has the at least one mobile phase container (102); wherein at least one of the at least one mobile phase container (102) is arranged with an upwardly directed outflow opening (112); wherein at least one of the at least one mobile phase container (102) is arranged with a downwardly directed outflow opening (112). Fluid supply device (100) according to one of the Claims 1 until 9 , having a fluid valve (114) which is arranged at a fluid inlet of the buffer container (104) and is designed to be movable with a movement of the buffer container (104). Fluid supply device (100) according to one of the Claims 1 until 10 , wherein the bridging mechanism (106) is designed for, in particular automatic or controlled, return transfer for supplying the fluid delivery device (20) with mobile phase from at least one mobile phase container (102) if a temporarily interrupted supply of the fluid delivery device (20) with mobile phase from the at least one mobile phase container (102) is restored. Fluid supply device (100) according to one of the Claims 1 until 11 , having a refilling mechanism (116) for, in particular automatic or controlled, refilling of the buffer container (104) with mobile phase when a temporarily interrupted supply of the fluid delivery device (20) with mobile phase from the at least one mobile phase container (102) is restored. Fluid supply device (100) according to one of the Claims 1 until 12th , having a membrane (118) in the buffer container (104) which divides the buffer container (104) into a partial volume (120) which carries mobile phases and a partial volume (122) which does not carry mobile phases. Fluid supply device (100) according to Claim 13 , having a pressure setting device (124) which is designed to act in a pressure-setting manner on the membrane (118) and on a fluid valve (114) arranged at a fluid inlet of the buffer container (104). Fluid supply device (100) according to one of the Claims 1 until 14th , comprising an air bubble discharge device (140) for discharging an air bubble from the buffer container (104) away from the fluid delivery device (20). Fluid supply device (100) according to one of the Claims 1 until 15th , having two split and recombined parallel flow paths (128, 130) between the at least one mobile phase container (102) and the fluid conveying device (20), the buffer container (104) being arranged on or in one of the flow paths (128, 130), in particular comprising at least one control valve (131-133) in at least one of the flow paths (128, 130) for controlling whether mobile phase flows through the one flow path (128) or through the other flow path (130). Fluid supply device (100) according to one of the Claims 1 until 16 , having a ventilation device (136) for ventilating the at least one mobile phase container (102), wherein the ventilation device (136) has a ventilation line (138) between a positive pressure source (27) and the at least one mobile phase container (102) and a ventilation line (136) opening or a closing ventilation valve (139) which is designed to be movable with a movement of the buffer container (104). Sample separation device (10) for separating a sample in a mobile phase, the sample separation device (10) comprising: a fluid conveying device (20) for conveying the sample and the mobile phase into which the sample is to be introduced, a sample separating device (30) for separating the sample introduced into the mobile phase; and a fluid supply device (100) according to one of the Claims 1 until 17th for supplying the fluid delivery device (20) with mobile phase from at least one mobile phase container (102). Sample separator (10) according to Claim 18 , having at least one of the following features: the sample separation device (30) is designed as a chromatographic separation device, in particular as a chromatography separation column; the sample separation device (10) is configured to analyze at least one physical, chemical and / or biological parameter of at least one fraction of the sample; the sample separation device (10) has at least one from the group consisting of a device for chemical, biological and / or pharmaceutical analysis, a liquid chromatography device, a gas chromatography device and an HPLC device; the fluid delivery device (20) is set up to drive the mobile phase at a high pressure; the fluid delivery device (20) is set up to drive the mobile phase with a pressure of at least 100 bar, in particular at least 500 bar, further in particular at least 1000 bar; the sample separation device (10) is configured as a microfluidic device; the sample separation device (10) is configured as a nanofluidic device; the sample separation device (10) has a detector (50) for detecting the separated sample; the sample separation device (10) has an injector (40) for injecting the sample into the mobile phase, the sample separation device (10) has a sample fractionator (60) for fractionating the separated sample. A method for supplying a fluid delivery device (20) of a sample separation device (10) with a mobile phase from at least one mobile phase container (102), the method comprising: Storing a buffer amount of mobile phase in a buffer container (104) in or on a fluidic path between the at least one mobile phase container (102) and the fluid delivery device (20); and temporary supply of the fluid delivery device (20) with mobile phase from the buffer container (104) when the at least one mobile phase container (102) is temporarily decoupled from the provision of mobile phase.

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