Fluid coupling device with elastic structure deformable by sealing element

Abstract

A fluid coupling device (200) is disclosed, provided by a first fluid structure (210) and a second fluid structure (215) and located between the first fluid structure (210) and the second fluid structure (215) and configured to fluidly couple the first fluid structure (210) and the second fluid structure (215). The first fluid structure (210) has a first channel (238) configured to direct fluid and open at a first opening (233) located at a first surface (235) of the first fluid structure (210). The second fluid structure (215) has a second channel (248) configured to direct fluid and open at a second opening (243) located at a second surface (245) of the second fluid structure (215). The fluid coupling device (200) includes a sealing element (270) positioned between the first surface (235) and the second surface (245). The first fluid structure (210) includes a first resilient structure (258) located in and / or below the first surface (235). When the first surface (235) and the second surface (245) are pressed against each other, the first resilient structure (270) elastically deforms the first resilient structure (285), the first opening (233) and the second opening (243) are in fluid communication with each other, allowing fluid communication between the first channel (238) and the second channel (248), and the sealing element (270) fluidly seals the fluid communication between the first channel (238) and the second channel (248).

Description

Technical Field

[0001] This invention relates to fluid coupling between a first fluid structure and a second fluid structure, particularly in high-performance liquid chromatography applications. Background Technology

[0002] In high-performance liquid chromatography (HPLC), liquids must typically be supplied at very controlled flow rates (e.g., in the range of a few microliters to a few milliliters per minute) and high pressures (typically 20–100 MPa, 200–1000 bar, and currently up to 200 MPa, 2000 bar), at which the compressibility of the liquid becomes significant. For liquid separation in an HPLC system, the mobile phase of a sample fluid (e.g., a chemical or biological mixture) containing complexes to be separated is driven through a stationary phase (e.g., column packing material), thereby separating the different complexes of the sample fluid, which can then be identified. The term "complex" as used herein should encompass complexes that may contain one or more different components.

[0003] Typically, a mobile phase (e.g., a solvent) is pumped under high pressure through a chromatographic column containing a packed medium (also called the packing material or stationary phase). As the sample is carried through the column by the liquid flow, different complexes (each with a different affinity for the packing medium) move through the column at different speeds. Complexes with a greater affinity for the stationary phase move through the column more slowly than those with a smaller affinity, and this speed difference causes the complexes to separate from each other as they pass through the column. The stationary phase is subjected to mechanical forces, specifically generated by a hydraulic pump that typically pumps the mobile phase from the upstream connection to the downstream connection of the column. Due to the flow, a relatively high pressure drop is generated on the column, depending on the physical properties of the stationary and mobile phases.

[0004] The mobile phase containing the separated complexes exits the column and passes through a detector, which records and / or identifies the molecules, for example, by spectrophotometric absorbance measurements. A two-dimensional curve, called a chromatogram, can be plotted showing the detector measurements relative to elution time or volume, and the complexes can be identified from the chromatogram. For each complex, the chromatogram displays individual curve characteristics, also known as “peaks.” Efficient separation of complexes by column is advantageous because it provides measurements that produce well-defined peaks with sharp inflection points at maximum values ​​and narrow base widths, allowing for excellent resolution and reliable identification and quantification of the mixture components. Broad peaks (so-called “internal band broadening”) or poor system performance (so-called “external band broadening”) caused by poor column performance are undesirable, as they may allow minor components of the mixture to be masked by the major components and remain unidentified.

[0005] Fluid couplers are widely used to provide fluid coupling between two or more fluid components, such as for coupling a capillary to a device, for coupling two devices, and so on. Such fluid couplers can be used in various locations within the flow path (e.g., within an HPLC system).

[0006] For example, planar microfluidic structures are described in WO 0078454A1, DE 19928412A1, US 6814846, WO 9849548, US 6280589, or WO9604547. WO 2009121410A1, by the same applicant, discloses a fluid coupling device with a planar fluid structure. Summary of the Invention

[0007] The object of this invention is to provide an improved fluid coupling device between fluid structures, particularly for HPLC applications. This object is achieved by the independent claims. Other embodiments are illustrated by the dependent claims.

[0008] An embodiment provides a fluid coupling device comprising a first fluid structure and a second fluid structure located between the two fluid structures and configured to fluidly couple the first and second fluid structures. The first fluid structure has a first channel configured to guide fluid and opens at a first opening located on a first surface of the first fluid structure. The second fluid structure has a second channel configured to guide fluid and opens at a second opening located on a second surface of the second fluid structure. The fluid coupling device includes a sealing element positioned between the first and second surfaces. The first fluid structure includes a first resilient structure located in and / or below the first surface. When the first and second surfaces are pressed against each other, the first resilient structure elastically deforms, and the first and second openings fluidly communicate with each other, thereby allowing fluid communication between the first and second channels, and the sealing element fluidly seals the fluid communication between the first and second channels. This allows for a reliable fluid seal of the fluid coupling device, which is repeatable in the sense that fluid coupling can be repeatedly enabled and disabled, for example, by pressing the first and second fluid structures together and releasing the pressure between them. Furthermore, this can allow for the avoidance or at least reduction of deformation of the sealing element.

[0009] In one embodiment, at least one of the first fluid structure and the second fluid structure is a planar structure. This allows for reliable and hermetically sealed coupling of the planar structure, for example when applying microfluidic planar structures with extremely small physical dimensions (particularly for guiding fluid channels).

[0010] In one embodiment, the first fluid structure is provided by a plurality of layers fixedly joined to each other, wherein a first channel is provided by a gap between two of the plurality of layers. This layered structure allows for the provision of a first resilient structure by appropriately arranging, forming, and constructing one or more of the plurality of layers.

[0011] In one embodiment, the second fluid structure is provided by a plurality of layers fixedly joined to each other, wherein the second channel is provided by a gap between two of the plurality of layers. This layered structure allows for the provision of a second resilient structure by appropriately arranging, forming, and constructing one or more of the plurality of layers.

[0012] In one embodiment, at least one of the first fluid structure and the second fluid structure comprises or is composed of one or more of the following materials: metals, particularly high-grade steels (e.g., 316L, MP35N, 304), ceramics, particularly alumina, manganese oxide, zirconium oxide, aluminum nitrate, polymers, particularly PEEK, ULTEM, PEAK, PEKK, PEI, etc.

[0013] In one embodiment, the sealing element has an annular shape, preferably a concentric annular shape. This allows for simplification in improving sealing performance, since the sealing element, for example, concentrically surrounds the corresponding opening of the corresponding fluid structure.

[0014] In one embodiment, the sealing element protrudes beyond at least one of the first and second surfaces, at least before the first and second surfaces are pressed against each other.

[0015] In one embodiment, the sealing element is part of or attached (e.g., fixed) to one of the first and second surfaces, preferably by an extrusion or distribution process. Every suitable attachment type known in the art can be applied, from simply placing the sealing element on the respective surface, to fixing the sealing element to the respective surface (e.g., by gluing), to distributing the sealing element (e.g., printing, splattering, etc.) on the respective surface (e.g., as part of a manufacturing process).

[0016] In one embodiment, the sealing element comprises or is composed of one or more of the following materials: ductile and printable polymeric compounds, particularly PEEK, ULTEM, PEAK, PEKK, PEI, etc.

[0017] In one embodiment, a first resilient structure is disposed below a region of the first surface, and a sealing element abuts against the first surface in that region when the first and second surfaces are pressed against each other.

[0018] In one embodiment, the first elastic structure is provided by a first membrane and a first void (e.g., channel, hollow space, cavity, gap, etc.) beneath the first membrane. The first membrane is part of a first surface, and when the sealing element causes the first elastic structure to elastically deform, the first membrane elastically deforms into the first void.

[0019] In one embodiment, the first void may be subjected to pressure, preferably by supplying pressurized fluid into the first void, in order to modify the elastic properties of the first elastic structure. This can allow for adjustment and / or control of the elastic properties of the elastic structure, for example, based on the pressure in the fluid paths of the first and second channels. In one embodiment, using the same fluid flowing in the fluid paths of the first and second channels (e.g., the mobile phase in an HPLC system) to apply pressure to the void can result in automatic adjustment of the sealing force and / or performance based on actual sealing requirements.

[0020] In one embodiment, the second fluid structure includes a second elastic structure. This allows for the distribution of deformation provided by the sealing element between the first and second fluid structures, and / or adjustment and / or control of such deformation. The second elastic structure can be configured substantially the same as the first elastic structure, for example, in the sense of a symmetrical configuration (e.g., with respect to the sealing element between the first and second elastic structures).

[0021] In one embodiment, the second elastic structure is provided by a second membrane and a second void (e.g., channel, hollow space, cavity, gap, etc.) beneath the second membrane. The second membrane is part of the second surface, and when the sealing element causes the second elastic structure to elastically deform, the second membrane elastically deforms into the second void.

[0022] In one embodiment, the second void may be subjected to pressure, preferably by supplying pressurized fluid into the second void, in order to modify the elastic properties of the second elastic structure. This can allow for adjustment and / or control of the elastic properties of the elastic structure, for example, based on the pressure in the fluid paths of the first and second channels. In one embodiment, using the same fluid flowing in the fluid paths of the first and second channels (e.g., the mobile phase in an HPLC system) to apply pressure to the void can result in automatic adjustment of the sealing force and / or performance based on actual sealing requirements.

[0023] In one embodiment, the fluid coupling device includes a force applicator, such as a thread, cam, or expansion medium, configured to press a first surface and a second surface against each other.

[0024] In one embodiment, when the first surface and the second surface are pressed against each other, the first opening and the second opening are adjacent to each other and substantially aligned.

[0025] In one embodiment, the sealing element fluidly seals the fluid communication between the first channel and the second channel in a pressure range of up to 2000 bar and above.

[0026] In one embodiment, at least one of the first fluid structure and the second fluid structure is a planar structure. The first fluid structure is provided by a plurality of layers fixedly joined to each other, a first channel is provided by a first gap between two of the plurality of layers, and the plurality of layers are preferably made of a metallic material. A first surface is provided by an outer layer of the plurality of layers, and a first elastic structure is provided by a portion of the outer layer and a second gap below that portion of the outer layer. The portion of the outer layer above the gap is configured to act as a membrane that can elastically deform into the gap when the sealing element causes the first elastic structure to elastically deform. Such embodiments can be provided using so-called microfluidic (MMF) structures, which are multilayer structures comprising, for example, two or more metal sheets joined together by diffusion bonding, as described, for example, in the aforementioned WO2009121410A1 or WO 2017025857A1 of the same applicant.

[0027] In one embodiment, a separation system is provided for separating complexes of a sample fluid in a mobile phase. The fluid separation system includes: a mobile phase driver, preferably a pumping system adapted to drive the mobile phase through the fluid separation system; a separation unit, preferably a liquid chromatography column adapted to separate complexes of a sample fluid in the mobile phase; a first fluid structure for guiding the fluid only; a second fluid structure for guiding the fluid; and a fluid coupling device (according to any of the foregoing embodiments) for fluidly coupling the first fluid structure to the second fluid structure.

[0028] In one embodiment, the separation system further includes: a sample injector adapted to introduce sample fluid into the mobile phase; a detector adapted to detect the separated complex of the sample fluid; a collection unit adapted to collect the separated complex of the sample fluid; a data processing unit adapted to process data received from the fluid separation system; and a degassing device for degassing the mobile phase.

[0029] In one embodiment, a method for fluidly coupling a first fluid structure to a second fluid structure is disclosed. The first fluid structure has a first channel configured to guide fluid and open at a first opening located on a first surface of the first fluid structure. The second fluid structure has a second channel configured to guide fluid and open at a second opening located on a second surface of the second fluid structure. The method includes: positioning a sealing element between the first and second surfaces; and pressing the first and second surfaces against each other such that the sealing element elastically deforms an elastic structure in and / or beneath the first surface, the first and second openings being in fluid communication with each other, thereby allowing fluid communication between the first and second channels, and the sealing element fluidly sealing the fluid communication between the first and second channels.

[0030] Embodiments of the present invention can be implemented based on the most commonly available HPLC systems, such as the Agilent 1220, 1260 and 1290 Infinity LC series (provided by the applicant, Agilent Technologies).

[0031] One embodiment of an HPLC system includes a pumping device with a piston that reciprocates within a pump working chamber to compress a liquid in the pump working chamber to a high pressure, under which the compressibility of the liquid becomes apparent.

[0032] One embodiment of an HPLC system includes two pumping devices coupled in series or parallel. In series, as disclosed in EP309596A1, the outlet of the first pumping device is coupled to the inlet of the second pumping device, and the outlet of the second pumping device provides the pump outlet. In parallel, the inlet of the first pumping device is coupled to the inlet of the second pumping device, and the outlet of the first pumping device is coupled to the outlet of the second pumping device, thereby providing the pump outlet. In either case, the liquid outlet of the first pumping device is phase-shifted relative to the liquid outlet of the second pumping device, preferably substantially 180 degrees, such that only one pumping device supplies liquid to the system while the other (e.g., from a supply source) draws in liquid, thereby allowing a continuous flow at the output. However, it is clear that the two pumping devices can also operate in parallel (i.e., simultaneously) at least during certain transition phases, for example, to provide a smoother (more) transition of the pumping cycle between the pumping devices. The phase shift can be varied to compensate for pulsations in the liquid flow due to the compressibility of the liquid. The use of three piston pumps with a phase shift of approximately 120 degrees is also known. Other types of pumps are also known and can be used in conjunction with this invention.

[0033] The separation apparatus preferably includes a chromatographic column providing the stationary phase. This column can be a glass, metal, ceramic, or composite tube (e.g., 50 μm to 5 mm in diameter and 1 cm to 1 m in length) or a microfluidic column (as disclosed in EP 1577012 A1 or the Agilent 1200 series HPLC-Chip / MS system provided by the applicant). Individual components are retained differently by the stationary phase and separated from each other, while they propagate through the column at different rates with the eluent. At the ends of the column, they are eluted at least partially separated from each other. The eluent can also be collected in a series of fractions throughout the chromatography process. The stationary phase or adsorbent in column chromatography is typically a solid material. The most commonly used stationary phase in column chromatography is silica gel, followed by alumina. Cellulose powder has been frequently used in the past. Ion exchange chromatography, reversed-phase chromatography (RP), affinity chromatography, or expanded bed adsorption (EBA) are also possible. The stationary phase is typically a finely ground powder or gel and / or microporous for increased surface area, which may be specifically chemically modified, but fluidized beds are used in EBA.

[0034] The mobile phase (or eluent) can be a pure solvent or a mixture of different solvents. It may also contain additives, i.e., a solution of the additives in a solvent or solvent mixture. The retention rate of the target compound and / or the amount of mobile phase used for chromatography can be selected, for example, adjusted. The mobile phase can also be selected to allow for efficient separation of different complexes. The mobile phase may include an organic solvent typically diluted with water, such as methanol or acetonitrile. For gradient operations, water and organic matter are delivered in separate containers, from which a gradient pump delivers the 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 the aforementioned solvents.

[0035] The sample fluid can include any type of process liquid, such as natural samples like juice, bodily fluids like blood plasma, or it can be the result of a reaction such as that from fermentation broth.

[0036] The fluid is preferably a liquid, but may also be a gas and / or a supercritical fluid (such as that used in supercritical fluid chromatography-SFC disclosed, for example, in US 4,982,597A).

[0037] The pressure in the mobile phase can be 2-200 MPa (20 to 2000 bar), particularly 10-150 MPa (100 to 1500 bar), and even more particularly 50-120 MPa (500 to 1200 bar).

[0038] HPLC systems may also include detectors for detecting separated compounds in a sample fluid, fractionation units for outputting separated compounds from the sample fluid, or any combination thereof. Further details of the HPLC systems described above are disclosed regarding the Agilent HPLC family provided by the applicant, Agilent Technologies.

[0039] Embodiments of the present invention may be embodied or supported, in part or in whole, by one or more suitable software programs, which may be stored on any type of data carrier or executed by any suitable data processing unit. The software programs or routines may preferably be in or applied by a control unit.

[0040] In the context of this application, the term "fluid sample" can specifically refer to any liquid and / or gaseous medium, and optionally also includes solid particles to be analyzed. Such a fluid sample may include multiple fractions of molecules or particles to be separated, such as biomolecules like proteins. Because separating a fluid sample into fractions involves specific separation criteria (e.g., mass, volume, chemical properties, etc.), and separation is performed according to these criteria, each separated fraction can be further separated by another separation criterion (e.g., mass, volume, chemical properties, etc.), thereby separating individual fractions or separating them into multiple subfractions.

[0041] In the context of this application, the term "fraction" can specifically refer to a group of molecules or particles in a fluid sample that have been separated based on specific properties (such as mass, volume, chemical properties, etc.). However, the molecules or particles associated with a fraction may still have some degree of heterogeneity, which may necessitate further separation according to another separation criterion.

[0042] In the context of this application, the term "subfraction" can specifically refer to all groups of molecules or particles associated with a particular fraction that still differ from one another with respect to a certain property (e.g., mass, volume, chemical properties, etc.). Therefore, compared to the separation criteria used for the first separation, another separation criterion used for the second separation allows for further separation of these groups from one another by applying other separation criteria, thereby obtaining further separated subfractions.

[0043] In the context of this application, the term "downstream" can specifically mean that a fluid component located downstream of another fluid component will only interact with the fluid sample or its components after interacting with other fluid components (and thus arranged upstream). Therefore, the terms "downstream" and "upstream" refer to the overall flow direction of the fluid sample or its components, but do not necessarily imply a direct, uninterrupted fluid connection from upstream to downstream system components.

[0044] In the context of this application, the term "sample separation apparatus" can specifically refer to any apparatus capable of separating different components of a fluid sample by applying a certain separation technique. In particular, when configured for two-dimensional separation, such a sample separation apparatus may include two separation units. This means that the sample, or any part or subset thereof, is first separated according to a first separation criterion and subsequently separated according to a second separation criterion, the first and second separation criteria being the same or different.

[0045] The term "separation unit" can specifically refer to a fluid component through which a fluid sample is guided, and which is configured such that, upon guiding the fluid sample through the separation unit, some of the fluid sample or its components will be at least partially separated into different groups of molecules or particles (referred to as fractions or subfractions, respectively) according to some selection criterion. An example of a separation unit is a liquid chromatography column, which is capable of collecting different fractions of a fluid sample that selectively delays flow.

[0046] In the context of this application, the term "fluid driver" or "mobile phase driver" can specifically refer to any type of pump or fluid flow source or supplier configured to conduct a mobile phase and / or fluid sample along a fluid path. A corresponding fluid supply system can be configured to meter two or more fluids in a controlled ratio and supply the resulting mixture as the mobile phase. Multiple solvent supply lines can be provided, each fluidly connected to a corresponding reservoir containing the corresponding fluid. A proportioning device is provided between the solvent supply lines and the inlet of the fluid driver, configured to adjust the solvent composition by sequentially connecting selected solvent supply lines to the inlet of the fluid driver, wherein the fluid driver is configured to draw fluid from the selected solvent supply lines and supply a mixture of fluids at its outlet. More specifically, one fluid driver can be configured to provide a mobile phase flow that drives or carries a fluid sample through a corresponding separation unit, while another fluid driver can be configured to provide a further mobile phase flow that drives or carries a fluid sample or a portion thereof through another separation unit after processing by the corresponding separation unit. Attached Figure Description

[0047] Other objects and numerous incidental advantages of the invention will be readily appreciated and better understood by referring to the following more detailed description of embodiments taken in conjunction with the accompanying drawings. Substantially or functionally equivalent or similar features will be referred to by the same reference numerals. The illustrations in the drawings are schematic.

[0048] Figure 1 A liquid separation system 10 according to an embodiment of the present invention is shown, which is, for example, used for high performance liquid chromatography (HPLC).

[0049] Figure 2 schematically illustrates an exemplary embodiment of the coupler 200 according to the present invention.

[0050] Figure 3 illustrates several exemplary embodiments according to the present invention. Detailed Implementation

[0051] Now refer to the attached diagram for more details. Figure 1 A general schematic diagram of the liquid separation system 10 is shown. Pump 20 typically receives the mobile phase from solvent supplier 25 via degasser 27, which degass the mobile phase and thus reduces the amount of dissolved gas therein. Pump 20, acting as the mobile phase driver, drives the mobile phase through a separation device 30 (e.g., a chromatographic column) that includes a stationary phase. A sample dispenser 40 (also called a sample introduction device, sample injector, etc.) is provided between pump 20 and separation device 30 to apply or add (generally referred to as sample introduction) a portion of one or more sample fluids to the flow of the mobile phase (indicated by reference numeral 200, see also Figure 2). The stationary phase of separation device 30 is adapted to separate complexes of the sample fluid (e.g., a liquid). Detector 50 is provided for detecting the complexes of the separated sample fluid. A fractionation unit 60 may be provided for discharging the complexes of the separated sample fluid.

[0052] While the mobile phase can consist of only one solvent, it can also be a mixture of multiple solvents. Such mixing can be low-pressure mixing and positioned upstream of pump 20, so that drive 20 has already received and pumped the mixed solvent as the mobile phase. Alternatively, pump 20 can be composed of multiple separate pumping units, each receiving and pumping a different solvent or mixture, such that mixing of the mobile phase (received by separation unit 30) occurs at high pressure and downstream of (or as part of) pump 20. The composition of the mobile phase (mixture) can remain constant over time (so-called isocratic mode) or vary over time (so-called gradient mode).

[0053] A data processing unit 70, which may be a conventional PC or workstation, can be coupled (as indicated by the dashed arrow) to one or more devices in the liquid separation system 10 to receive information and / or control operation. For example, the data processing unit 70 can control the operation of pump 20 (e.g., set control parameters) and receive information from it about actual operating conditions (e.g., output pressure, flow rate, etc. at the pump outlet). The data processing unit 70 can also control the operation of solvent supplier 25 (e.g., monitor the level or amount of available solvent) and / or degasser 27 (e.g., set control parameters such as vacuum level), and can receive information from it about actual operating conditions (e.g., solvent composition supplied over time, flow rate, vacuum level, etc.). The data processing unit 70 can further control the operation of sample dispenser 40 (e.g., control sample introduction or synchronization of sample introduction with the operating conditions of pump 20). The separation device 30 can also be controlled by the data processing unit 70 (e.g., select a specific flow path or column, set operating temperature, etc.), and in response, send information (e.g., operating conditions) to the data processing unit 70. Accordingly, detector 50 can be controlled by data processing unit 70 (e.g., regarding spectral or wavelength settings, setting time constants, starting / stopping data acquisition), and information (e.g., regarding detected sample complexes) can be sent to data processor 70. Data processing unit 70 can also control the operation of fractionation unit 60 (e.g., combining data received from detector 50) and provide data back. Finally, data processing unit can also process and evaluate data received from the system or a portion thereof to represent the data in an appropriate form for further interpretation.

[0054] Fluid couplers are widely used to provide fluid coupling between two or more fluid components, such as for coupling a capillary to a device, for coupling two devices, and so on. Such fluid couplers can be used at various locations within the flow path, for example in... Figure 1 In some embodiments, this occurs between the solvent supply 25 and the fractionation unit 60. For example, a fluid coupler can be used to couple a capillary leading from the degasser 27 to the pump 20, a flow path from the pump 20 to the sample dispenser 40 (e.g., another capillary), another flow path between the sample dispenser 40 and the separation device 30 (e.g., a microfluidic structure), and so on. It will be apparent in the art that such a fluid coupler can be used virtually anywhere in the fluid flow path where fluid coupling between the various physical entities is required or utilized.

[0055] Figure 2 schematically illustrates an exemplary embodiment of the coupler 200 according to the present invention. The fluid coupler 200 includes a first fluid structure 210 and a second fluid structure 215, each configured to guide fluid and coupled to the other. Figure 2AThe fluid coupler 200 is shown in a three-dimensional diagram, in which the first fluid structure 210 is separated from the second fluid structure 215, for example, in a state where they are not yet coupled together. Figure 2B To correspond to Figure 2A A two-dimensional cross-sectional view of the fluid coupler 200 in its uncoupled state is shown. Figure 2C Similarly, using a two-dimensional section diagram (according to) Figure 2B However, the fluid coupler 200 is shown in an assembled state that provides fluid coupling between the first fluid structure 210 and the second fluid structure 215.

[0056] As shown in FIG2, the first fluid structure 210 and the second fluid structure 215 may each be part of a corresponding fluid device (and, for example, protrude laterally from such fluid device) as indicated by the corresponding through regions 220 and 225. Such a fluid device can be any type of device configured to process fluid. In the exemplary embodiment of FIG2, the first fluid structure 210 and the second fluid structure 215 should each be a corresponding fluid conduit configured to guide fluid. The first fluid structure 210 and / or the second fluid structure 215 may extend across the corresponding through regions 220 and 225. Alternatively, the first fluid structure 210 and / or the second fluid structure 215 may extend from the corresponding fluid device as corresponding connectors to provide connection and / or fluid coupling of the corresponding fluid device, for example, to another fluid device.

[0057] In the embodiment of Figure 2, the first fluid structure 210 (in) Figure 2A Both the first fluid structure 210 (best visible in the middle) and the second fluid structure 215 are configured as planar structures. The first fluid structure 210 has a circular profile 230 and includes a first fluid port 233 located at the center of the contact surface 235 (in the best visible middle). Figure 2B and Figure 2C (best visible in the middle). The position of the first fluid port 233 is preferably in a predetermined relationship with the profile 230. The first fluid port 233 and the fluid channel 238 ( Figure 2B (As shown by the dashed line in the diagram) fluid connection, fluid channel 238 can provide a fluid connection between fluid port 233 and (not shown) fluid device.

[0058] The second fluid structure 215 (also) has a circular profile 240 (in) Figure 2A (best visible in the middle) and includes a second fluid port 243 located at the center of the contact surface 245 (in Figure 2A (Best visible in Figure 2). The position of the second fluid port 243 is also preferably in a predetermined relationship with the outline 240. The second fluid port 243 is fluidly connected to the fluid channel 248 (not visible in Figure 2), which can provide a fluid connection between the fluid port 243 and a fluid device (not shown).

[0059] The first fluid structure 210 is adapted to press against another planar coupling member of another fluid device (such as the second fluid structure 215). Therefore, a fluid connection is established between the fluid ports 233 and 243 of the two planar coupling members of the first fluid structure 210 and the second fluid structure 215.

[0060] The first fluid structure 210 and / or the second fluid structure 215 can be implemented, for example, as a multilayer structure comprising two or more layers (preferably metal or plastic), which can preferably be bonded together, for example, by diffusion bonding.

[0061] For example, the first fluid structure 210 and / or the second fluid structure 215 can be implemented as a so-called metal microfluidic (MMF) structure, which is a multilayer structure comprising, for example, two or more metal sheets bonded together by diffusion, as described in, for example, the aforementioned WO 2009121410A1 or WO 2017025857A1 of the same applicant.

[0062] like Figure 2B and Figure 2C The most visible, planar first fluid structure 210 is made of three metal sheets 250, 253, and 255. (As shown...) Figure 2B and Figure 2C The second fluid structure 215, best visible in the center, can also be made of three metal sheets 260, 263, and 265. The metal sheets 250-255 and 260-265 can be, for example, titanium or stainless steel sheets, having a thickness ranging from approximately 0.05 mm to up to single-digit millimeters. To process the metal sheets 250-255 and 260-265, techniques such as electrochemical or chemical milling can be employed. Electrochemical or chemical milling can be used, for example, to form the outer contour of the metal sheets, or to form fluid channels 238 and 248, or both. Alternatively, the fluid channels 238 and 248 can be formed by cutting grooves in the (intermediate) metal sheets 253 and 263. Furthermore, alternatively, a stamping process can be used to form the fluid channels 238 and 248. Fluid ports 233 and 243 can be formed by cutting through holes in the corresponding (outer) metal sheets 235 and 245. When set in an MMF structure, fluid ports 233 and 243 can have a diameter in the range of 0.1-1 mm.

[0063] After metal sheets 250-255 and corresponding metal sheets 260-265 have been processed, they can be bonded together. According to a preferred embodiment, diffusion welding is used to bond the metal sheets. In diffusion welding, a multilayer structure comprising two or more stacked metal sheets is placed in a vacuum furnace for several hours, whereby the metal sheets are pressed against each other under contact pressure. Preferably, the stacked metal sheets are subjected to a temperature below their melting point, and more preferably to a temperature between 400°C and 1050°C, depending on the metals to be bonded. By applying heat, vacuum, and contact pressure to the stacked metal sheets, diffusion of metal atoms is enhanced, and strong covalent bonds are formed between adjacent metal sheets. Therefore, a multilayer structure with liquid-tight fluid channels can be obtained.

[0064] Returning to Figure 2, the second fluid structure 215 also includes a sealing element 270, which in the illustrated embodiment has an annular shape and is concentrically located around the second fluid port 243. For example... Figure 2B In the most visible position, the sealing element 270 protrudes beyond the contact surface 245 of the second fluid structure 215, as shown by X. The height X is preferably chosen to be less than the height Y of the second fluid structure 215, and more preferably, X is significantly less than Y. The sealing element 270 is arranged and configured such that when the first fluid structure 210 and the second fluid structure 215 are pressed against each other (e.g., ... Figure 2C (As shown) provides a fluid seal so that fluid ports 233 and 243 are in liquid-tight communication with each other.

[0065] The second fluid structure 215 also includes an elastic structure 275 below the sealing element 270. The elastic structure 275 is configured to press the first fluid structure 210 and the second fluid structure 215 against each other (e.g., when they are pressed together). Figure 2C As shown, the sealing element 270 is elastically deformed.

[0066] In the exemplary embodiment of FIG2, the elastic structure 275 is provided by, for example, a void 278 in a metal sheet 265. The void 278 is preferably disposed below the entire area of ​​the sealing element 270 abutting or attached to the contact surface 245. In the embodiment shown in FIG2, the sealing element 270 has an annular shape and is concentrically located around the second fluid port 243, and the void 278 also has an annular shape and is concentrically located around the second fluid port 243.

[0067] A portion of the metal sheet 265 between the gap 278 and the contact surface 245 acts as a membrane 279, for example, when the first fluid structure 210 and the second fluid structure 215 are pressed against each other (e.g. Figure 2C As shown), the sealing element 270 can deform the membrane 279 into the gap 278.

[0068] The elastic structure 275 is preferably designed such that the deformation of the membrane 279 provided by the sealing element 270 is substantially elastic, preferably with little or no plastic deformation.

[0069] In the exemplary embodiment of FIG2, the gap 278 is designed to be wider than the area where the sealing element 270 abuts against the contact surface 245. Figure 2B In the diagram, the area where the sealing element 270 abuts against the contact surface 245 is indicated by arrow 280, while the width of the gap 278 is indicated by arrow 282.

[0070] As further shown in Figure 2, the first fluid structure 210 may also include another elastic structure 285 in the region where the sealing element 270 will abut against or is abutting against the contact surface 235. The elastic structure 285 is also configured to react when the first fluid structure 210 and the second fluid structure 215 are pressed against each other (e.g., ...). Figure 2C As shown, the sealing element 270 is elastically deformed.

[0071] In the exemplary embodiment of FIG2, the elastic structure 285 is provided by a void 288 in the metal sheet 255. The void 288 is preferably disposed below the entire area of ​​the sealing element 270 abutting or attached to the contact surface 235. A portion of the metal sheet 255 between the void 288 and the contact surface 235 acts as a membrane 289, for example, when the first fluid structure 210 and the second fluid structure 215 are pressed against each other (e.g.) Figure 2C As shown), the sealing element 270 can deform the membrane 289 into the gap 288.

[0072] The elastic structure 285 is preferably designed such that the deformation of the membrane 289 provided by the sealing element 270 is substantially elastic, preferably with little or no plastic deformation.

[0073] In the exemplary embodiment of FIG2, the gap 288 is designed to be wider than the area where the sealing element 270 abuts against the contact surface 235. Figure 2B In the middle, the width of gap 288 is indicated by arrow 290.

[0074] like Figure 2C As schematically shown, when the first fluid structure 210 and the second fluid structure 215 are pressed against each other, the sealing element 270 will deform the two membranes 279 and 289. This allows the contact surfaces 235 and 245 to at least partially abut against each other, preferably at least in the region surrounding the first fluid port 233 to the second fluid port 243, in order to provide a liquid-tight coupling between the first fluid port 233 and the second fluid port 243, as... Figure 2CAs indicated by the arrow in the diagram. This also allows for the avoidance or at least reduction of dead volume. Such dead volume can occur when the first fluid port 233 and the second fluid port 243 do not fully penetrate each other but do penetrate into the space between contact surfaces 235 and 245.

[0075] Although the exemplary embodiment of FIG2 shows a first fluid structure 210 with elastic structure 275 and a second fluid structure 215 with elastic structure 285, it is clear that liquid-tight coupling can also be provided with only one of the elastic structures 275 and 285. Accordingly, a plurality of elastic structures can be applied to the corresponding fluid structures.

[0076] The elastic properties of the elastic structures 275 and 285 can be designed to be controlled, for example, by the geometry of the corresponding voids 288 (e.g., widths 282 and 290), the thickness and / or shape of the membranes 279 and 289, the material of the membranes 279 and 289, etc.

[0077] The sealing performance between the first fluid structure 210 and the second fluid structure 215 can also be designed and / or improved by selecting a material for at least one of the contact surfaces 235 and 245 and / or by applying a coating to at least one of the contact surfaces 235 and 245.

[0078] The elastic structures 275, 285 (or at least one of them) allow for the avoidance or reduction of extrusion, crushing, creep and / or flow of the sealing element 270 when the first fluid structure 210 and the second fluid structure 215 are pressed against each other.

[0079] The fluid coupler 210 allows for the coupling and disengagement of a preferably repeatable first fluid structure 210 and a second fluid structure 215. The elastic structures 275, 285 (or at least one of them) allow for maintaining a liquid-tight seal even after multiple couplings and disengagements.

[0080] The sealing element 270 is preferably made of a polymer material, such as PTFE or PEEK. Alternatively, a precious metal, such as gold, may be used.

[0081] Although the exemplary embodiment of FIG2 shows the sealing element 270 being attached to or as part of the second fluid structure 215, the sealing element 270 may also be attached to or as part of the first fluid structure 210. Alternatively, the sealing element 270 may be a loose component that can be inserted—as needed—between the first fluid structure 210 and the second fluid structure 215.

[0082] The gaps 288, 288 can be provided, for example, by an etching process or by removing a portion of the corresponding sheet.

[0083] The gaps 288 and 288 are preferably configured to not have any fluid contact with the fluid channels 238 and 248, ensuring strict separation from the fluid flow in the fluid channels 238 and 248.

[0084] In one embodiment, at least one of the voids 288, 288 is coupled to a pressure source that allows adjustment of the elastic properties of the respective elastic structures 275, 285. This pressure source can be a pump or fluid supplied to the void. For example... Figure 1 In one embodiment of the liquid separation system 10, at least one fluid in the voids 288, 288 is coupled to a mobile phase or a mobile phase supply driven by the pump 20. This allows for increasing the elastic pressure on the sealing element 270 while simultaneously increasing the pressure in the mobile phase, and vice versa.

[0085] Obviously, the concept of the fluid coupler 200 shown in FIG2 is not limited to the exemplary embodiment shown. For example, instead of two planar structures, only one of the first fluid structure 210 and the second fluid structure 215 may be configured as a planar structure. Alternatively, neither the first fluid structure 210 nor the second fluid structure 215 may be configured as a planar structure.

[0086] Although the concept of fluid coupler 200 is very effective for fluid coupling planar structures, it is sufficient as long as the corresponding contact areas (such as contact areas 235 and 245 in FIG. 2) to provide coupling between the first fluid structure 210 and the second fluid structure 215 are sufficiently flat to allow contact areas to abut.

[0087] Furthermore, the concept of fluid coupler 200 is not limited to providing a single fluid coupling between adjacent fluid ports (such as the first fluid port 233 and the second fluid port 243 in FIG2), but can also provide and implement multiple fluid couplings.

[0088] Figure 3 illustrates several exemplary embodiments according to the present invention.

[0089] Figure 3A A fluid structure 300 with two fluid ports 305 and 310 is shown, each fluid port surrounded by corresponding sealing elements 315 and 320. The fluid structure 300 can be used to couple with one or two individual fluid structures, such as or similar to the first fluid structure 210 and the second fluid structure 215 of FIG. 2. Alternatively, the fluid structure 300 can be coupled to a fluid structure (not shown) of a similar design and also having two ports to provide fluid coupling with fluid ports 305 and 310. As previously explained, at least one of the fluid structures to be coupled needs to provide a corresponding elastic structure to be deformed by the corresponding sealing element when the two fluid structures are compressed against each other.

[0090] Figure 3BIt shows something similar to Figure 3A An embodiment of the fluid structure 300 in the middle embodiment, but with four fluid ports 325, 330, 323 and 235, each port being surrounded by corresponding sealing elements 336, 337, 338 and 339.

[0091] Figure 3C It shows something similar to Figure 3A and Figure 3B An embodiment of the fluid structure 300, but with seven fluid ports 340-346, each port surrounded by a corresponding sealing element 350-356. Compared to Figure 3A and Figure 3B In the embodiment, the fluid ports are arranged longitudinally, and the fluid ports 340-346 are arranged in a circular manner.

[0092] Figure 3D Different embodiments with fluid structure 300 are shown, which may resemble either the first fluid structure 210 or the second fluid structure 215, at least in the respective contact areas 233 and 245. However, a tubular conduit 360 is fluidly coupled to the fluid port 365 of the fluid structure 300, for example, by providing suitable channels known in the art. The tubular conduit 360, which may be a capillary, may be circumferentially held by a fitting 370. Mechanical and fluid coupling and connection between the tubular conduit 260 and the fluid structure 300 may be provided as known in the art. The fluid port unit 65 is surrounded by a sealing element 375.

Claims

1. A fluid coupling device (200) comprising a first fluid structure (210) and a second fluid structure (215), and configured to fluidly couple the first fluid structure (210) to the second fluid structure (215), wherein, The first fluid structure (210) has a first channel (238) configured to guide fluid and open at a first opening (233) located at a first surface (235) of the first fluid structure (210). The second fluid structure (215) has a second channel (248) configured to guide fluid and opens at a second opening (243) located at a second surface (245) of the second fluid structure (215). The fluid coupling device (200) includes a sealing element (270) positioned between the first surface (235) and the second surface (245), and The first fluid structure (210) includes a first elastic structure (285) located in and / or below the first surface (235). When the first surface (235) and the second surface (245) are pressed against each other, The sealing element (270) causes the first elastic structure (285) to elastically deform. The first opening (233) and the second opening (243) are in fluid communication with each other, thereby allowing fluid communication between the first channel (238) and the second channel (248), and The sealing element (270) fluid seals the fluid communication between the first channel (238) and the second channel (248); The first elastic structure (285) is provided by a first membrane (289) and a first gap (288) below the first membrane (289), wherein the first membrane (289) is part of the first surface (235), and the first membrane (289) elastically deforms into the first gap (288) when the sealing element (270) causes the first elastic structure (285) to elastically deform.

2. The fluid coupling device (200) according to claim 1, comprising at least one of the following: The first fluid structure (210) and / or the second fluid structure (215) are planar structures; The first fluid structure (210) is provided by a plurality of layers (250-255) fixedly joined to each other, wherein, The first channel (238) is provided by the gap between two of the plurality of layers (250-255); The second fluid structure (215) is provided by a plurality of layers (260-265) fixedly joined to each other, wherein the second channel (248) is provided by the gap between two of the plurality of layers (260-265); At least one of the first fluid structure (210) and the second fluid structure (215) comprises or is composed of one or more of the following materials: metals, including: alumina, manganese oxide, zirconium oxide, aluminum nitrate; ceramics; and polymers, including PEEK, ULTEM, PEKK, PEI.

3. The fluid coupling device (200) according to claim 1 or 2, comprising at least one of the following: The sealing element (270) has an annular shape; The sealing element (270) protrudes beyond at least one of the first surface (235) and the second surface (245) at least before the first surface (235) and the second surface (245) are pressed against each other; The sealing element (270) is part of one of the first surface (235) and the second surface (245) or is attached to one of the first surface (235) and the second surface (245) by a pressing or distributing process; The sealing element (270) comprises or is composed of one or more of the following materials: ductile and printable polymeric compounds: PEEK, ULTEM, PEKK, PEI.

4. The fluid coupling device (200) according to claim 1 or 2, wherein: The first elastic structure (285) is disposed below the area of ​​the first surface (235), and when the first surface (235) and the second surface (245) are pressed against each other, the sealing element (270) abuts against the first surface (235) in the area.

5. The fluid coupling device (200) according to claim 1, wherein: The first void (288) can be subjected to pressure, and the elastic properties of the first elastic structure (285) can be modified by providing pressurized fluid into the first void (288).

6. The fluid coupling device (200) according to claim 1 or 2, wherein: The second fluid structure (215) includes a second elastic structure (275).

7. The fluid coupling device (200) according to claim 6, comprising at least one of the following: The second elastic structure (275) is provided by a second membrane (279) and a second void (278) beneath the second membrane (279), wherein, The second membrane (279) is part of the second surface (245), and when the sealing element (270) causes the second elastic structure (275) to elastically deform, the second membrane (279) elastically deforms into the second void (278); The second void (278) can be subjected to pressure, and the elastic properties of the second elastic structure (275) can be modified by providing pressurized fluid into the second void (278).

8. The fluid coupling device (200) according to claim 1 or 2 further comprises: A force applicator, including a thread, a cam, or an expansion medium, is configured to press the first surface (235) and the second surface (245) against each other.

9. The fluid coupling device (200) according to claim 1 or 2, comprising at least one of the following: When the first surface (235) and the second surface (245) are pressed against each other, the first opening (233) and the second opening (243) are adjacent to each other and substantially aligned; The sealing element (270) fluidly seals the fluid communication between the first channel (238) and the second channel (248) in a pressure range of up to 2000 bar.

10. The fluid coupling device (200) according to claim 1 or 2, wherein: At least one of the first fluid structure (210) and the second fluid structure (215) is a planar structure. The first fluid structure (210) is provided by a plurality of layers (250-255) fixedly joined to each other, the first channel (238) is provided by a first gap (288) between two of the plurality of layers (250-255), and the plurality of layers (250-255) are made of a metallic material. The first surface (235) is provided by the outer layer of the plurality of layers (250-255), and The first elastic structure (285) is provided by a portion of the outer layer and a second void (278) below the portion of the outer layer, wherein the portion of the outer layer above the void is configured to act as a membrane that can elastically deform into the void when the sealing element (270) causes the first elastic structure (285) to elastically deform.

11. A liquid separation system (10) for separating complexes of a sample fluid in a mobile phase, the liquid separation system (10) comprising: The mobile phase driver (20) is a pumping system adapted to drive the mobile phase through the liquid separation system (10). The separation unit (30) is a chromatographic column adapted to separate the complex of the sample fluid in the mobile phase. The first fluid structure (210) is used to guide the fluid. The second fluid structure (215) is used to guide the fluid, and The fluid coupling device (200) according to any one of claims 1 to 10 is used to fluidly couple the first fluid structure (210) with the second fluid structure (215).

12. The liquid separation system (10) according to claim 11, further comprising at least one of the following: A sample dispenser (40) adapted to introduce the sample fluid into the mobile phase; Detector (50), adapted to detect complexes of the separated sample fluid; Collection unit (60), adapted to collect the complex of the separated sample fluid; A data processing unit (70) adapted to process data received from the liquid separation system (10); Degassing device (27) is used to degas the mobile phase.

13. A method for fluidly coupling a first fluid structure (210) with a second fluid structure (215), wherein, The first fluid structure (210) has a first channel (238) configured to guide fluid and open at a first opening (233) located on a first surface (235) of the first fluid structure (210), and the second fluid structure (215) has a second channel (248) configured to guide fluid and open at a second opening (243) located on a second surface (245) of the second fluid structure (215), the first fluid structure (210) including a first elastic structure (285) located in and / or below the first surface (235), the method comprising: A sealing element (270) is positioned between the first surface (235) and the second surface (245), and The first surface (235) and the second surface (245) are pressed against each other, such that the sealing element (270) causes the elastic structure located in and / or below the first surface (235) to elastically deform, the first opening (233) and the second opening (243) to be in fluid communication with each other, thereby allowing fluid communication between the first channel (238) and the second channel (248), and the sealing element (270) fluidly seals the fluid communication between the first channel (238) and the second channel (248); The first elastic structure (285) is provided by a first membrane (289) and a first gap (288) below the first membrane (289), wherein the first membrane (289) is part of the first surface (235), and the first membrane (289) elastically deforms into the first gap (288) when the sealing element (270) causes the first elastic structure (285) to elastically deform.

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