Passive Damping Gradient Proportional Valve

Abstract

A gradient proportional valve for liquid chromatography is disclosed, comprising a plurality of inlet ports configured to receive a plurality of fluids; a manifold connected to each of the plurality of inlet ports and configured to mix the plurality of fluids in a controlled manner to provide a fluid composition, the manifold comprising a plurality of fluid conduits inside the manifold, each of the plurality of fluid conduits receiving a fluid through a corresponding one of the plurality of inlet ports, each of the plurality of fluid conduits being operably connected to a corresponding actuating mechanism, the actuating mechanism being configured to open and close each of the plurality of fluid conduits in a controlled manner, a common outlet port being configured to receive the fluid composition, and a passive fluid damping system being configured to attenuate undesirable fluid pressure pulses in the manifold, wherein at least one of the plurality of fluid conduits is flexible.

Description

[0001] Related Applications

[0002] This application is a non-provisional patent application claiming priority to U.S. Provisional Patent Application 62 / 941,236, entitled “Gradient Proportioning Valve,” filed on November 27, 2019, which is incorporated herein by reference. Technical Field

[0003] The present invention generally relates to gradient proportional valves. More particularly, the present invention relates to gradient proportional valves having passive fluid damping features and associated systems and methods. Background Art

[0004] Gradient proportional valves (GPVs) are known for use in low pressure mixing liquid chromatography systems (i.e., quaternary systems). U.S. Patent No. 5,862,832 describes an exemplary prior art GPV. Specifically, the GPV is responsible for setting the desired solvent composition in the system. A typical GPV includes multiple solenoid valves mounted on a common manifold that open and close at precise times relative to the system pump cycle. When the GPV solenoid valves are opened and closed, pressure pulses are introduced into the system. The start and end of the intake stroke during the pump cycle also cause pressure pulses. Such pressure pulses may cause undesirable oscillations in the composition error of the chromatography system. Therefore, these oscillations reduce the composition accuracy and performance of the liquid chromatography system. Summary of the invention

[0005] In one embodiment, a gradient proportional valve for liquid chromatography comprises: a plurality of inlet ports configured to receive a plurality of fluids; a manifold connected to each of the plurality of inlet ports and configured to mix the plurality of fluids in a controlled manner to provide a fluid composition, the manifold comprising a plurality of fluid conduits within the manifold, each of the plurality of conduits receiving a fluid through a corresponding one of the plurality of inlet ports, each of the plurality of fluid conduits being operably connected to a corresponding actuating mechanism configured to open and close each of the plurality of fluid conduits in a controlled manner; a common outlet port configured to receive the fluid composition; and a passive fluid damping system configured to attenuate unwanted fluid pressure pulses in the manifold, wherein the passive fluid damping system comprises at least one of the plurality of fluid conduits comprising a flexible portion.

[0006] Additionally or alternatively, each of the plurality of fluid conduits comprises a flexible portion.

[0007] Additionally or alternatively, the flexible portion is made of a material selected from the group consisting of polytetrafluoroethylene (PTFE), fluorinated ethylene propylene (FEP) and perfluoroelastomer (FFKM).

[0008] Additionally or alternatively, the gradient proportioning valve further comprises a plurality of corresponding actuation mechanisms, wherein each of the plurality of corresponding actuation mechanisms is a solenoid valve, and wherein the flexible portion of at least one of the plurality of fluid conduits is located upstream of one of the solenoid valves.

[0009] Additionally or alternatively, the gradient proportional valve further includes a single accumulator chamber inside the manifold, wherein each of the plurality of fluid conduits provides fluid to the single accumulator chamber, wherein the single accumulator chamber includes a diaphragm disposed in the single accumulator chamber, a first side of the diaphragm is exposed to the interior of the single accumulator chamber, and a second side of the diaphragm is exposed to the outside of the manifold.

[0010] Additionally or alternatively, the gradient proportioning valve further comprises a plurality of modular receiver ports within the manifold, each of the plurality of receiver ports being in fluid communication with a respective one of the plurality of fluid conduits.

[0011] Additionally or alternatively, the gradient proportioning valve further comprises at least one modular flat bottom fitting plug received in the receiving port, the flat bottom being exposed to the received fluid from a corresponding one of the plurality of fluid conduits.

[0012] Additionally or alternatively, the gradient proportional valve further comprises at least one modular diaphragm assembly plug received in the receiving port, the diaphragm assembly plug creating an accumulator chamber inside the manifold in fluid communication with a corresponding one of the plurality of fluid conduits.

[0013] Additionally or alternatively, the gradient proportional valve further includes at least one accumulator chamber within the manifold, wherein at least one of the plurality of fluid conduits provides fluid to the at least one accumulator chamber, wherein the fluid damping system includes the at least one accumulator chamber having a ribbed diaphragm disposed in the fluid damping system.

[0014] Additionally or alternatively, the fluid damping system includes at least one of the respective actuation mechanisms having a flexible seal made of at least one of PTFE, FEP and FFKM.

[0015] Additionally or alternatively, the fluid damping system includes at least one of the plurality of fluid conduits comprising a curved pulse damping flow geometry configured to mitigate fluid pressure pulses.

[0016] Additionally or alternatively, the fluid damping system includes a plurality of beads positioned within at least one cavity in the manifold or within at least one of the plurality of fluid conduits, the plurality of beads being configured to reduce pulse amplitude.

[0017] In another embodiment, a method for mixing fluids in liquid chromatography includes: providing a gradient proportioning valve; receiving a plurality of fluids in a plurality of inlet ports of the gradient proportioning valve; mixing the plurality of fluids in a controlled manner within a manifold of the gradient proportioning valve to provide a fluid composition, the manifold comprising a plurality of fluid conduits, wherein at least one of the plurality of fluid conduits is a flexible fluid conduit; opening and closing each of the plurality of fluid conduits in a controlled manner; outputting the fluid composition from a common outlet port of the gradient proportioning valve; and attenuating the unwanted fluid pressure pulses in the manifold using the flexible fluid conduits.

[0018] Additionally or alternatively, the controlled opening and closing of each of the plurality of fluid conduits is performed by a respective solenoid valve, and the method further comprises absorbing, using the flexible fluid conduit upstream of the at least one of the respective solenoid valves, unwanted fluid pressure pulses generated by the opening and closing of at least one of the respective solenoid valves.

[0019] Additionally or alternatively, each of the plurality of fluid conduits is a flexible fluid conduit, and the method further comprises attenuating the unwanted fluid pressure pulses in the manifold using each of the plurality of flexible fluid conduits.

[0020] Additionally or alternatively, the method further includes utilizing a single accumulator chamber having a diaphragm disposed therein to attenuate unwanted fluid pressure pulses in the manifold.

[0021] Additionally or alternatively, the method further includes attenuating the unwanted fluid pressure pulses using a flexible seal made of at least one of PTFE, FEP, and FFKM.

[0022] Additionally or alternatively, the method further comprises using a tortuous flow geometry within the manifold to mitigate the unwanted fluid pressure pulses.

[0023] Additionally or alternatively, the method further comprises attenuating the unwanted fluid pressure pulses using a plurality of beads located within at least one cavity of the manifold or within at least one of the plurality of fluid conduits.

[0024] In another embodiment, a liquid chromatography system includes a gradient proportional valve for liquid chromatography, the gradient proportional valve including a plurality of inlet ports, the plurality of inlet ports being configured to receive a plurality of fluids; a manifold connected to each of the plurality of inlet ports, configured to mix the plurality of fluids in a controlled manner to provide a fluid composition, the manifold including a plurality of fluid conduits inside the manifold, each of the plurality of conduits receiving a fluid through a corresponding one of the plurality of inlet ports, each of the plurality of fluid conduits being operably connected to a corresponding actuating mechanism, the corresponding actuating mechanism being configured to open and close each of the plurality of fluid conduits in a controlled manner; a common outlet port, the common outlet port being configured to receive the fluid composition; and a passive fluid damping system configured to attenuate unwanted fluid pressure pulses in the manifold, wherein the passive fluid damping system includes at least one of the plurality of fluid conduits, the fluid conduit including a flexible portion. The liquid chromatography system further includes an injector; a separation column; and a detector. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] The above and other advantages of the present invention may be better understood by referring to the following description in conjunction with the accompanying drawings, in which the same reference numerals refer to the same elements and features in each of the drawings. For clarity, not every element is labeled in every drawing. The drawings are not necessarily drawn to scale, but emphasis is placed on illustrating the principles of the present invention.

[0026] Figure 1 Depicted is a block diagram of a liquid chromatography apparatus according to one embodiment.

[0027] Figure 2 Depicted is a perspective view of a gradient proportioning valve according to one embodiment.

[0028] Figure 3 Depicted is a Figure 2 A side cross-sectional view of a gradient proportional valve.

[0029] Figure 4 Depicted is a schematic diagram of a gradient proportioning valve with a flexible fluid conduit according to one embodiment.

[0030] Figure 5 Depicted is a schematic diagram of a gradient proportioning valve having four inlets according to one embodiment.

[0031] Figure 6 Depicted is a side cross-sectional view of a solenoid valve having an energy absorbing solenoid armature stop according to one embodiment.

[0032] Figure 7 Depicted is a schematic diagram of another gradient proportional valve having a single accumulator chamber according to one embodiment.

[0033] Fig. 8A Depicted is a side cross-sectional view of a portion of a modular gradient proportional valve according to one embodiment.

[0034] Figure 8B Depicted is a method for incorporating Fig. 8A Side cross-sectional view of a flat bottom mounting plug in a modular gradient proportional valve.

[0035] Figure 8C Depicted is a method for incorporating Fig. 8A A side cross-sectional view of a diaphragm assembly plug in a modular gradient proportional valve.

[0036] Fig.9A Depicted is a top view of a ribbed diaphragm for a gradient proportional valve according to one embodiment.

[0037] Fig. 9B Depicted is a Fig.9A Side view of the costal diaphragm.

[0038] Fig. 10A Depicted is a side view of a diffusion-bonded gradient proportional valve according to one embodiment.

[0039] Fig. 10B Depicted is a diagram taken at arrow 10B according to one embodiment. Fig. 10A Top cross-sectional view of a diffusion-coupled gradient proportional valve. DETAILED DESCRIPTION

[0040] Reference in this specification to "one embodiment" or "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present teachings. References to specific embodiments within this specification are not necessarily all referring to the same embodiment.

[0041] The gradient ratio valve accommodates the flow of fluid from an external reservoir into the valve for mixing in the proper proportions to form a liquid composition. In a practical embodiment, such a valve may include four inlet valves interfaced to a common outlet, as shown below. Figure 2The embodiment shown in shows two inlet valves interfaced to a common outlet. In terms of functionality, each inlet valve can be a normally closed solenoid-actuated diaphragm valve that switches in a controlled manner to provide the appropriate amount of fluid required to mix the liquid composition. The function of the entire valve is to provide a continuous flow of a compositionally accurate mixture of components (such as solvents in high pressure liquid chromatography (HPLC) embodiments). The mixture can be provided from the common outlet under flow conditions without interfering with the flow rate of the fluid input system and without changing or otherwise affecting the quality / composition of the fluid input for mixing.

[0042] Embodiments of gradient proportional valve as herein described can be configured to passively weaken or otherwise reduce the pressure pulses that occur due to the opening and closing of the passage in the fluid system of the valve and the passage in the valve itself. It has been found that such pressure pulses cause large sinusoidal oscillations in composition errors. Passive fluid damping can include not utilizing active, powered on and / or controlled equipment to weaken these fluid pressure pulses. Therefore, gradient proportional valve as herein described can be configured to provide improved composition accuracy within the entire solvent composition range. The improved composition accuracy may be particularly important under higher flow rates.

[0043] Figure 1 is a block diagram of an exemplary liquid chromatography system 100 suitable for preparative scale or process scale liquid chromatography according to one embodiment of the present invention. System 100 is an exemplary system in which a gradient proportioning valve may be included according to embodiments described herein. Apparatus 100 includes four solvent reservoirs 1A, 1B, 1C, 1D, a gradient proportioning valve 2, an inlet manifold valve 3, a pump 4, a solvent mixer 5, an injector 8, a separation column 6, a detector 7, and a control unit 9. Gradient proportioning valve 2 represents a valve including one or more damping features described herein. Thus, gradient proportioning valve 2 may be Figures 2 to 10B Any of the gradient proportioning valves shown in and described below.

[0044] In operation, the gradient proportioning valve 2 and the pump 4 select and extract one or more solvents from the reservoirs 1A, 1B, 1C, 1D in response to the control of the control unit 9. The gradient proportioning valve 2 can be operated in response to the control of the control unit 9 to provide a selected solvent composition that optionally varies in time, for example to achieve gradient mode chromatography. The solvent mixer 5 is any suitable mixer, including known passive and active mixers. The syringe is any suitable syringe 8, including known syringes, for injecting a sample into the solvent stream. The syringe 8 is optionally arranged at an alternative position in the solvent flow path, as will be understood by a person skilled in the art of liquid chromatography. The inlet manifold valve 3 is connected to the outlet pipe from the gradient proportioning valve 2 and to two inlet pipes (connected to the pump 4) to supply the solvent to the two piston chambers. The inlet manifold valve 3 optionally includes a sample syringe to inject the sample into the solvent before it enters the pump 4. The control unit 9, including, for example, a personal computer or workstation, receives data and / or provides control signals to, for example, the gradient proportioning valve 2, the pump inlet manifold 3, the pump 4 and / or the detector 7 through wired and / or wireless communication. The control unit 9 supports, for example, automation of sample processing. In various illustrative embodiments, the control unit 9 is implemented in software, firmware and / or hardware (eg, as an application specific integrated circuit). The control unit 9 includes and / or communicates with a storage component.

[0045] Suitable implementations of the control unit 9 include, for example, one or more integrated circuits, such as microprocessors. In some alternative embodiments, a single integrated circuit or microprocessor includes the control unit 9 and other electronic parts of the device 100. In some embodiments, the one or more microprocessors implement software that enables the functions of the control unit 9. In some embodiments, the software is designed to run on general-purpose devices and / or dedicated processors dedicated to the functions described herein.

[0046] In some embodiments of system 100, control unit 9 includes user interface to support the interaction with control unit 9 and / or other parts of system 100. For example, interface is configured to accept control information from user and provide information about system 100 to user. User interface is for example used to set system control parameters and / or provide diagnosis and troubleshooting information to user. In one embodiment, user interface provides networked communication between system 100 and user that is located in operating environment local or away from operating environment. In some embodiments, user interface is used to modify and update software. In view of the description of illustrative embodiments provided herein, it is obvious to those of ordinary skill in separation field that various other configurations and implementations of control unit can be utilized in other embodiments of the present invention to provide automatic control of the chromatogram of process scale and preparation scale.

[0047] Pump 4 can be configured to provide solvent at a pressure of at least 500psi, or 1,000psi, or 5,000psi, 10,000psi or greater. The pump includes any suitable piston-based pump, including known pumps, such as those available from Waters Corporation, Milford, Mass. Column 6 is any chromatographic column suitable for process-scale and preparative-scale chromatography. The column includes, for example, any medium suitable for such purposes, including known media. The adsorbent material is selected from any suitable adsorbent material, including known materials, such as a mixture of silicon dioxide or silicon dioxide and a copolymer, such as an alkyl compound. The solvent is any solvent suitable for the desired separation process, including known solvents.

[0048] Again, the system 100 described above is intended to be an exemplary liquid chromatography system in which various embodiments of a gradient ratio valve may be deployed. However, the gradient ratio valve described herein may be implemented in any system that performs gradient fluid mixing. For example, in a liquid chromatography quaternary system, after solvent reservoirs 1A, 1B, 1C, 1D, the next component that the solvent enters may be a degasser chamber. From there, the solvent may enter the gradient ratio valve 2. After the gradient ratio valve 2, the solvent may then enter the pump (i.e., without an inlet manifold valve) through a check valve. It is contemplated that any liquid chromatography system configuration that may deploy a gradient ratio valve may be used in conjunction with the principles described herein.

[0049] Reference now Figure 2 , shows a perspective view of a gradient proportional valve 2A according to one embodiment. The gradient proportional valve 2A includes accumulators 19A, 19B, which are located directly adjacent to the switching valves 17A, 17B on the side closest to the reservoirs 10A, 10B. It should be understood that embodiments of the gradient proportional valve 2A may include two additional accumulators and switching valves (not shown) located on the two open sides of the gradient proportional valve 2A, thereby connecting the gradient proportional valve 2 to two additional reservoirs, for example, Figure 1 1C, 1D shown in the drawings. Each of the accumulators 19A, 19B may include a soft-walled flexible plastic tube 50 of generally circular cross-section. As shown, the accumulator tube 50 may be adapted to slide snugly over a rigid plastic connector 52 at the end closest to the valve inlet. A connecting tube 54 may be implemented at the opposite end of the accumulator tube to maintain a relatively long length of flow conduit 56 connecting the valve to the reservoir 1A, 1B. The end of the accumulator tube adjacent to the connecting tube may be made to have a generally flattened ellipse 55 cross-section, which may allow significant internal volume changes to occur in the accumulator tube with little change in pressure, thereby allowing the accumulator to overcome the effects of hydraulic inertia.

[0050] Figure 3 Depicted is a Figure 2 A side cross-sectional view of a gradient proportioning valve 2A. The gradient proportioning valve 2A includes a valve manifold 10 that accommodates the flow of fluid from an external reservoir (not shown). For the sake of clarity of the discussion below, the illustrative valve described herein has the ability to mix only two input fluid streams. However, the features described herein may be applied to valves that mix, for example, four or more input fluid streams. The input fluid stream to be mixed is received from the reservoir and introduced into the valve at the inlet port 12. Fluid from a corresponding reservoir, such as a solvent used in HPLC as known in the art, flows into the corresponding inlet port 12 and then flows into the corresponding accumulator volume or cavity 16 through the corresponding inlet conduit 14 in the manifold 10.

[0051] The overall accumulator cavity 16 and the inlet port 12 and inlet conduit 14 are appropriately sized as a function of the flow rate of the valve application. The cavity 16 is tapered, with a conical base opposite the inlet conduit 14. The cavity is shaped to maximize the surface area of ​​the diaphragm (for compliance), and the inlet conduit 14 is positioned to allow for optimal swept volume geometry. Therefore, the cavity 16 also has a smooth transition from a larger cross-section to a smaller cross-section. The placement of the cavity minimizes fluid resistance between the valve diaphragm 40 (discussed below) and the accumulator. Fluid flowing through the conduit 14 flows into the cavity 16 perpendicular to the tapered base to constrain the base or back of the cavity 16.

[0052] The accumulator diaphragm 18 is positioned at the conical base or back side of the chamber 16, opposite the inlet conduit 14. The diaphragm 18 in this illustrative embodiment is a 0.002 inch thick film formed of polytetrafluoroethylene (PTFE) laminated on each side with fluorinated ethylene propylene (FEP).

[0053] As with all components in the fluid path of this illustrative embodiment, the diaphragm is formed of a material that is functionally unaffected by various organic solvents and aqueous solutions of acids, bases, salts, surfactants, etc., and other phase modifiers that can be used in any mode of liquid chromatography. The diaphragm 18 implements a membrane or compliant member on the back side of the accumulator chamber 16 to allow internal volume changes in the chamber with little change in pressure. Thus, the valve can overcome the effects of hydraulic inertia, as with the less favorable accumulator tubes of the prior art. As will be appreciated by those skilled in the art, the compliance and damping of the diaphragm is optimized for the application flow characteristics.

[0054] An oversized bore 20 behind the back of the conical seat or accumulator chamber 16 is configured to receive the diaphragm 18 to tightly clamp and seal the diaphragm therein. A seating surface 22 inside the bore 20 provides an abutment against which the diaphragm rests. A sealing groove 24 is provided in the seating surface 22 and provides a portion of a single seal implemented in an embodiment according to the present invention. A cylindrical sealing plug 26 formed of stainless steel includes a sealing ridge 28 that fits tightly into the sealing groove 24 to seal the diaphragm in the bore 20 when the plug 26 engages against the seating surface 22 with the diaphragm sandwiched therebetween.

[0055] Preferably, the sealing plug 26 is sized to fit snugly and slidably within the bore 20. The plug 26 is held in place by a clamping plate 30 that is mechanically attached to the valve manifold, such as by screws 32. Additional mounting holes 33 are provided in the clamping plate 30 to facilitate mechanical fastening of the clamping plate to the valve manifold 10. In this illustrative embodiment, a resilient member, such as a bellows spring 34 or a washer, is provided between the sealing plug 26 and the clamping plate 30 to provide some resiliency.

[0056] The diaphragm according to the present invention overcomes hydraulic inertia while minimizing the volume of fluid in the valve exposed to possible air infiltration by limiting the surface area of ​​the diaphragm exposed to ambient air. Compared to the prior art in which the entire accumulator tube is exposed and the volume of fluid passing therethrough is affected by ambient air permeating the tube, the diaphragm according to the present invention is only exposed to the environment in a limited manner. An atmospheric port 36 is provided in the clamping plate 30 to admit ambient air behind the diaphragm 18. When the diaphragm needs to be exposed to ambient air to perform its intended function, the reduced surface area exposed in the atmospheric port significantly limits air permeation through the diaphragm.

[0057] As briefly described above, the input fluid stream to be mixed is received from the reservoir and introduced into the valve manifold 10 at the inlet port 12. The fluid from the respective reservoir flows into the respective inlet port 12 and then flows into the respective accumulator volume or cavity 16 through the respective inlet conduit 14 in the manifold 10. The inlet conduit 14 can be inside the housing of the gradient proportional valve 2A and can be a flexible conduit made of a compliant material, as described in more detail below. Therefore, the inlet conduit 14 can be configured to expand or contract due to the internal fluid pressure therein.

[0058] In the corresponding integral accumulator chamber 16, the fluid to be mixed encounters a flexible diaphragm that allows the internal volume in the chamber to change with little change in pressure, so that the valve can overcome the effects of hydraulic inertia. The fluid flows out of the chamber 16 through the chamber port 38, whereby the fluid can be obtained at the switched valve diaphragm 40. The chamber port 38 can be a flexible fluid conduit inside the housing or external body of the gradient proportional valve 2A. The chamber port 38 can be configured to expand or contract according to the fluid pressure of the fluid therein. The valve diaphragm reciprocates through a switching valve known in the art. The controlled switching of the valve diaphragm determines the proportion of the corresponding fluids received in the common port 42 in the valve manifold 10. The corresponding fluids are mixed in their corresponding proportions in the common port 42 and can be obtained at the outlet port 44 for downstream processing as known in the art. Similar to the chamber port 38 and the inlet conduit 14, the common port 42 can be located inside the housing or body of the gradient proportional valve 2A, and can be a flexible fluid conduit that is configured to expand or contract with changes in the fluid pressure therein. The compliance of the lumen port 38 and or the inlet conduit 14 and / or the common port 42 may include a passive fluid damping system configured to attenuate fluid pressure pulses as described herein.

[0059] Although only two input valves are described in the illustrative embodiments herein, it should be understood that the concepts according to the present invention may be implemented in valves having any number of inlet ports for mixing liquid compositions.

[0060] Although the diaphragms described herein are formed from a FEP-PTFE-FEP lamination, it should be understood that other materials may be implemented to implement the diaphragm, such as thin stainless steel, various composite materials, rubber, and the like.

[0061] While the sealing plug in the illustrative embodiment is a cylindrical plug formed of stainless steel, it should be understood that alternative sealing mechanisms may be implemented while allowing for ambient pressure behind the diaphragm, such as sponge-like materials, cylindrical composite materials, etc. In addition, while the sealing plug achieves a tight seal by having a sealing ridge that is located in a sealing groove in the bore that receives the plug, it should be understood that the groove may be located in the plug with the ridge located on the surface of the bore.

[0062] Therefore, the gradient proportional valve 2A includes a passive fluid damping system, which includes one or more passive damping mechanisms, systems or methods configured to passively weaken unwanted fluid pressure pulses in the manifold. Therefore, the gradient proportional valve 2A can be configured to weaken or otherwise reduce pressure pulses that occur due to the opening and closing of channels in the fluid system associated with the valve 2A and channels within the valve 2A itself. Specifically, the fluid damping system can be configured to passively weaken unwanted fluid pressure pulses generated by the solenoid valves 17A, 17B of the valve 2A. Therefore, the gradient proportional valve 2A can be configured to provide improved composition accuracy over the entire solvent composition range.

[0063] In one or more embodiments, the fluid damping system includes at least one of a plurality of fluid conduits, which includes a flexible portion. For example, any one of the inlet conduit 14, the cavity port 38 and / or the common port 42 may be made of a compliant material so that the fluid passes directly through a channel or conduit made of a compliant material. The compliance herein may include materials such as polytetrafluoroethylene (PTFE), fluorinated ethylene propylene (FEP) or perfluoroelastomer (FFKM) or materials with similar Young's modulus. The compliance herein defines a material that undergoes elastic deformation due to force or pressure under pressure experienced by a liquid chromatography system. Therefore, when a force is applied, the compliant material in the valve herein may bend when a force is applied, but return to its original shape after the force stops. Compliance may further allow channels 14, 38, 42 to expand as pressure increases, and to contract as pressure decreases. The compliant material herein may be configured to achieve force and motion transmission by deformation of the elastic body from the internal fluid pressure in the conduit. Thus, when a force or pressure is generated within the conduit, the compliance of the material will result in an elastic bulk deformation of the channel which does not cause permanent or plastic deformation. When the force or pressure is thereby reduced, the conduit may be configured to return to its original form.

[0064] The compliance of the channels described herein, including compliance in one or more of channels 14, 38, 42, can be configured to cause such elastic body deformation to occur under the pressure ranges found within those channels of the GPV. The operating pressure range in the GPV can be between -20.0 and 20 pounds per square inch (psi). The pressure pulse from valve actuation can be, for example, 5 psi or less. In an exemplary embodiment, the settling time after the pressure pulse can be less than one second. In other embodiments, the operating pressure range of the GPV can be narrower, such as between 10 psi and -15 psi. Likewise, the pressure pulse can even be less than 5 psi, for example, in the form of about 4 psi or about 3 psi. The settling time can also be less than 1 second; for example, .75 seconds or .5 seconds.

[0065] Additionally, exemplary compliances of the flexible channels 14, 38, 42 are contemplated. In one embodiment, the flexible channels 14, 38, 42 may have a compliance greater than .1 µL / psi (e.g., for each psi of pressure increase, the channel may expand to accommodate .1 µL or more). In some embodiments, the compliance may be at least .5 µL / psi, at least .75 µL / psi, or at least 1 µL / psi.

[0066] Therefore, the compliance of the channel can act as a fluid capacitor that attenuates pulses in the system. Figure 3 The embodiment shown, however, a flexible fluid conduit within the valve may be included on any valve embodiment described herein.Any contemplated gradient proportional valve configuration consistent with the embodiments described herein may include a flexible fluid conduit.

[0067] Additionally, in one or more embodiments, the fluid damping system includes at least one corresponding actuating mechanism having a flexible seal, for example made of a compliant material such as PTFE, FEP, or FFKM. Figure 3 In the illustrated embodiment, the tapered seal poppet valve (not shown) sealing the passage 42 at the solenoid switching valve diaphragm 40 (as known in the solenoid valve art) may be replaced or modified with a more compliant material. In one embodiment, an auxiliary seal may surround or otherwise modify the tapered seal poppet valve to absorb pulses when opening and / or closing the solenoid seal.

[0068] Figure 4 Describe the schematic diagram of the gradient proportional valve 2B with flexible fluid conduits 62, 66 according to one embodiment. The gradient proportional valve 2B is shown to include four inlet ports 60. Each corresponding inlet port 60 provides fluid through a flexible fluid conduit 62. The corresponding flexible fluid conduit 62 is configured to provide fluid from the corresponding inlet port 60 to the corresponding solenoid valve 64. Thereafter, the corresponding solenoid valve 64 provides fluid to another corresponding flexible fluid conduit 66. Then, the fluid can converge from the flexible fluid conduit 66 to a single outlet port 68. A single converging fluid conduit can also be provided before the single outlet port 68, and the outlet port can also be made of a compliant material. The flexible fluid conduit 62 and the flexible fluid conduit 66 can each be made of the same material described above with respect to the inlet conduit 14, the cavity port 38 and / or the common port 42.

[0069] and Figure 3Different, in this embodiment, some or all of the fluid conduits within the valve 2B can provide sufficient pressure damping through the compliant material in the passive fluid damping system, so that the accumulator chamber 16 is not unnecessary. In addition, in other embodiments, some but not all of the various fluid conduits inside the housing of the gradient proportional valve 2B are flexible. For example, only the fluid conduit 66 located downstream of the solenoid valve 64 can be flexible, while the upstream conduit 62 connecting the inlet 60 to the solenoid valve 64 can be made of a typical fluid channel material that is non-flexible and non-expanding under system pressure. Alternatively, only the fluid conduit upstream of the solenoid valve can be flexible.

[0070] In some embodiments, the flexible conduit may be particularly effective upstream of the solenoid valve. There, the flexible conduit may be configured to mitigate pressure pulses, act as a flow buffer, and improve response time. In other embodiments, the flexible conduit may be located after the solenoid valve, but before the mixing point in the GPV. Regardless of the embodiment, the flexible conduit is located before the mixing point of the GPV. After the mixing point, the flexible conduit may have a negative impact on solvent metering. In some embodiments, the entire conduit may be made of a compliant material, or the entire wall of the fluid channel is made of a compliant material, so that the pulse damping characteristics are consistent with the flow, rather than entering a separate accumulator chamber.

[0071] Figure 5 A schematic diagram of a gradient proportioning valve 2C having a manifold 110 is depicted according to one embodiment, which manifold may include the same or similar features as the manifold 10, but may have four inlet ports 112 for combining with a single outlet port 144. Each inlet port 112 is connected to a corresponding accumulator chamber 116 via a corresponding inlet conduit 114. As shown, the accumulator chamber may be attached or otherwise connected to the manifold 110 via a compression plate 116. The chamber port 38 connects the corresponding accumulator chamber 116 to the solenoid valves 117A, 117B, 117C, 117D and their corresponding switching valve diaphragms 140. After passing through the switching valve diaphragms 140 of the corresponding solenoid valves 117A, 117B, 117C, 117D, the fluid is received in the port 42, which is combined before the outlet port 144 for downstream processing.

[0072] In one or more embodiments, the fluid damping system includes a plurality of beads located within at least one cavity, such as the integral accumulator cavity 16 within the manifold 10. The plurality of beads may be spherical in shape, or may each be any rounded object configured to reduce the pulse amplitude of a fluid pressure pulse. The plurality of beads may additionally or alternatively be located within any fluid conduit, such as the inlet conduit 14, within the manifold 10 and / or within the cavity port 38 and / or the common port 42. The plurality of beads may be disposed within the manifold 10 such that they occupy the volume of any space in which they are present, such that the plurality of beads do not move significantly relative to the manifold 10 when the manifold 10 is moved, shaken, or otherwise subjected to forces.

[0073] In some embodiments, multiple beads may be disposed in the same manner (number of beads, size of beads, etc.) at the same location within each fluid path (i.e., the path from one of the inlet ports 12 to the outlet port 44). In other embodiments, each respective fluid path may include its own bead configuration. For example, a first fluid path from a first inlet port may include multiple beads of a first diameter in the accumulator chamber 16 of the first fluid path. A second fluid path may include no beads, while a third fluid path and a fourth fluid path may include beads of different diameters in their accumulator chambers 16. For any given fluid path, the fluid damping system may include any type of beads, beads of any size, beads of any material, and any amount of beads disposed at any location. Although reference has been made to Figure 5 A plurality of beads are described, but the plurality of beads described herein may be used in conjunction with any one or combination of the other gradient proportioning valve embodiments described herein.

[0074] Reference now Figure 6, shows a side cross-sectional view of a solenoid valve 117E having an energy absorbing solenoid armature stop 150 according to one embodiment. The solenoid valve 117E includes a solenoid 152 surrounding an armature 154. The armature 154 is disposed within a cavity 156 surrounding the armature 154. A spring mechanism 158 is located at the end of the cavity 156. When the solenoid 152 is activated, the armature 154 is configured to move toward the energy absorbing armature stop 150 to open the valve 117E and allow fluid to move from the fluid inlet 160 through the valve 117E to the fluid outlet 162. In this embodiment, the fluid damping system of the contemplated gradient proportional valve (such as valve 2A or 2B) includes an energy absorbing solenoid armature stop 150 located at the end of the armature 154 that would otherwise contact when the valve is in an open state. The energy absorbing armature stop 150 may be a deformable or compliant material configured to mitigate the hard stop of the armature 154 against the wall of the cavity 156 when the spring mechanism 158 is compressed. The solenoid armature stop 150 may be made of any polymeric, elastomeric, or composite material, such as, but not limited to, urethane, FFKM, silicone, etc. It should be understood that one or more of the solenoid valves 117E may be used in any of the gradient proportional valves described herein.

[0075] Figure 7 A schematic diagram of another gradient proportional valve 2D having a single accumulator chamber 316 is depicted according to one embodiment. The gradient proportional valve 2D includes a manifold 310 having four inlet ports 312, each of which is connected to a corresponding solenoid valve 317 through a corresponding inlet conduit 314. The solenoid valves 317 each include a port 342 that transfers fluid to the single accumulator chamber 316. The single accumulator chamber 316 includes a diaphragm disposed in the single accumulator chamber. Figure 3 As with the accumulator chamber 16 shown, a first side of the diaphragm may be exposed to the interior of the single accumulator chamber 316, while a second side of the diaphragm may be exposed to the exterior of the manifold 310. Thus, the single accumulator chamber 316 may be a flexible chamber and may be located before, after, or at the mixing point of the four fluid paths. In one embodiment, in addition to or in lieu of a flexible diaphragm disposed in the accumulator chamber, the entire accumulator chamber 316 may include a flexible wall. Furthermore, as described above, multiple beads may be located in a single accumulator chamber.

[0076] Fig. 8AA side cross-sectional view of a portion of a modular gradient proportional valve 2E according to one embodiment is depicted. The modular gradient proportional valve 2E includes an inlet port 412 that is fluidically connected to a modular receiver port 450. The cavity port 438 extends from the modular receiver port 450 to the solenoid diaphragm 440. The common port 442 extends from the solenoid diaphragm 440 to a mixing point, after which the fluid path extends to an outlet 444. The modular gradient proportional valve 2E includes a modular receiver port 450 inside the manifold 410. Although a single modular receiver port 450 is shown, it should be understood that two, three, four or more separate modular receiver ports 450 may be included, one modular receiver port for each fluid path. In other embodiments, a plurality of modular receiver ports 450 may be included in each separate fluid path. Each of the plurality of receiving ports may be configured to be in fluid communication with a fluid path or conduit in the manifold 410. The modular receiver port 450 may be threaded, for example, to allow easy removal or attachment of a modular assembly plug. Different mounting plugs may be attached to the same manifold 410 depending on the implementation, or plugs may be removed or added to the manifold as desired.

[0077] Figure 8B and Figure 8C Two exemplary modular mounting plugs are shown. Figure 8B Depicted is a schematic diagram of a device for incorporating a Fig. 8A 4E. The flat bottom mounting plug may be received in the modular receiving port 450 and may include, for example, threads or another attachment mechanism for integrating, attaching, connecting, or otherwise coupling the modular receiving port 450. When inserted and attached within the receiving port 450, the flat bottom 462 of the flat bottom mounting plug 460 may be exposed to the fluid path but may block fluid from entering the area occupied by the modular receiving port 450. This creates a bypass without the need to attenuate pressure pulses in a given fluid path, such as within a manifold.

[0078] Figure 8C Depicted is a device for incorporating a membrane 472 according to one embodiment. Fig. 8A 4E. The modular diaphragm assembly plug 470 can be received in the modular receiving port 450 and can include, for example, threads or another attachment mechanism for integrating, attaching, connecting or otherwise coupling the modular receiving port 450. The diaphragm assembly plug 470 can be configured to create an accumulator cavity that includes the same or similar structure as the accumulator cavity 16 described above, and is in fluid communication with a corresponding one of the fluid paths and / or fluid conduits within the manifold 410.

[0079] Using any combination of diaphragm mounting plugs 470 and flat bottom mounting plugs 460, the modular gradient proportional valve 2E can be configured to interchangeably receive a variety of mounting plugs for creating a customizable valve manifold according to the specific implementation desired. It is further contemplated that different types of diaphragm fittings with different characteristics are contemplated - some may include more compliant or less compliant diaphragms, some may or may not include beaded cavities, etc. Various modular combinations are contemplated.

[0080] Fig.9A Depicted is a top view of a ribbed diaphragm 500 for a gradient proportional valve according to one embodiment. Fig. 9B Depicted is a Fig.9A 5. The ribbed diaphragm 500 includes a geometric shape including a plurality of concentric ribs defining an inner circumference 540, a first concentric ring 530, a second concentric ring 520, and a third concentric ring 510. Fig. 9B As shown, the concentric rings get deeper as the diaphragm 500 approaches the center. The ribs in the diaphragm (where the concentric portions 510, 520, 530, 540 meet) can be flexible so that the diaphragm becomes deeper when subjected to pressure from one side. The ribs can be configured to provide further compliance to the diaphragm 500 while still maintaining a compact form. The compliance of the ribbed diaphragm can be configured to attenuate pressure pulses. The ribbed diaphragm 500 can be used on any diaphragm in any gradient proportional valve and / or its manifold described herein.

[0081] Fig. 10A Depicted is a side view of a diffusion-bonded gradient proportional valve 2F according to one embodiment. In this embodiment, the gradient proportional valve and / or its manifold includes two parts that are diffusely bonded together - a top manifold part 610A and a bottom manifold part 610B. By creating two separate manifold parts 610A, 610B and diffusing those parts together, the same internal geometry that cannot be processed using traditional methods utilizing a single block can be achieved. Valve 2F is shown as including three separate solenoid valves 617A, 617B, 617C, but a fourth valve (not shown) is hidden on the opposite surface of the manifold. Three separate fluid inlets 619A, 619B, 619C are shown, but the fourth inlet and outlet are all hidden behind the first inlet 618A in this side view.

[0082] Fig. 10B Depicted is a diagram taken at arrow 10B according to one embodiment. Fig. 10A1. A top cross-sectional view of a diffusion-bonded gradient proportional valve 2F. As shown, in this embodiment, the gradient proportional valve 2F includes a fluid conduit 642 that is curved to produce a pulse damping flow geometry that is configured to reduce fluid pressure pulses. Specifically, each of the fluid conduits 642 extends from a corresponding solenoid valve 617A, 617B, 617C, 617D to a mixing point 670.

[0083] Each of these fluid conduits 642 includes a first bend 650 that deviates the fluid conduit 642 from a straight line toward a mixing point 670. The bend may be at an angle greater than 90 degrees but less than 180 degrees. The second bend 652 may be an equal bend in the opposite direction of the first bend 650. The third bend 654 is also equal in degree to the first two bends 650, 652 and may bend the fluid conduit in the same direction as the second bend 652. The fourth bend 656 and the fifth bend 658 may each bend the fluid conduit in the same direction as the first bend 650, and the sixth final bend 660 may bend the fluid conduit back toward the mixing point 670 in the same direction as the second bend 652 and the third bend 654. Each of the bends 650, 652, 654, 656, 658, 660 may be at the same angle. The geometry created by the bends in the fluid conduit 642 can be configured to prevent pressure pulses caused by the opening and closing of the solenoid valves 617A, 617B, 617C, 617D from reaching the mixing point 670. It should be understood that the contemplated embodiments can include any tortuous flow geometry, including any number of bends for each respective fluid path. In some embodiments, the different fluid paths from each of the solenoid valves 617A, 617B, 617C, 617D can have bends of different shapes (or no bends at all), depending on the necessary implementation.

[0084] Embodiments of the present invention further contemplate the method for using principle described above to mix fluid.The method for mixing fluid may first include providing a gradient ratio valve consistent with one or more in principle described herein and / or a liquid chromatography system with this type of gradient ratio valve.The method may include receiving a plurality of fluids in a plurality of inlet ports of a gradient ratio valve, and mixing a plurality of fluids in a controlled manner in the manifold of a gradient ratio valve to provide a fluid composition, and the manifold comprises a plurality of conduits.The method may include opening and closing each in a plurality of conduits in a controlled manner, and outputting a fluid composition from the common outlet port of a gradient ratio valve.

[0085] The method may further include attenuating unwanted fluid pressure pulses in the manifold with a passive fluid damping system.

[0086] In some embodiments, opening and closing each of the plurality of fluid conduits in a controlled manner is performed by a corresponding solenoid valve, and the method further includes absorbing unwanted fluid pressure pulses generated by the opening and closing of the solenoid valves, the solenoid valves having an energy absorbing solenoid armature stop located in at least one of the corresponding solenoid valves.

[0087] In some embodiments, a method may include attenuating unwanted fluid pressure pulses in a manifold with at least one flexible fluid conduit.

[0088] In some embodiments, a method may include utilizing a single accumulator chamber having a diaphragm disposed therein to attenuate unwanted fluid pressure pulses in a manifold.

[0089] In some embodiments, a method may include removably inserting a plurality of modular assembly plugs into a plurality of corresponding modular receiving ports of a gradient proportioning valve, and attenuating unwanted fluid pressure pulses in a manifold using at least one of the plurality of modular assembly plugs.

[0090] In some embodiments, the method may include utilizing a ribbed diaphragm to attenuate unwanted fluid pressure pulses in the manifold. In some embodiments, the method may include utilizing a flexible seal made of at least one of PTFE, FEP, and FFKM to attenuate unwanted fluid pressure pulses.

[0091] In some embodiments, a method may include using a tortuous flow geometry within a manifold to mitigate unwanted fluid pressure pulses.

[0092] In still other embodiments, methods can include attenuating unwanted fluid pressure pulses with a plurality of beads positioned within at least one lumen of a manifold or within at least one of the plurality of fluid conduits.

[0093] In an exemplary embodiment, a method for mixing fluids may include providing a gradient proportional valve, receiving multiple fluids in multiple inlet ports of the gradient proportional valve, mixing multiple fluids in a controlled manner in a manifold of the gradient proportional valve to provide a fluid composition, the manifold including multiple fluid conduits. At least one of the multiple fluid conduits is a flexible fluid conduit. According to some embodiments, all of the multiple fluid conduits are flexible fluid conduits. The method further includes opening and closing each of the multiple fluid conduits in a controlled manner, outputting the fluid composition from a common outlet port of the gradient proportional valve, and weakening the unwanted fluid pressure pulses in the manifold with the flexible fluid conduit. In some embodiments, opening and closing each of the multiple conduits in a controlled manner is performed by a corresponding solenoid valve, so that the method includes absorbing the unwanted fluid pressure pulses generated by the opening and closing of at least one of the corresponding solenoid valves using a flexible fluid conduit located upstream of at least one of the corresponding solenoid valves. In addition, the method may include using a single accumulator chamber with a diaphragm disposed therein to weaken the unwanted fluid pressure pulses in the manifold. The method may also include using a flexible seal made of at least one of PTFE, FEP and FFKM to weaken the unwanted fluid pressure pulses. The method may further include using a tortuous flow geometry within the manifold to mitigate unwanted fluid pressure pulses. Additionally, the method may include utilizing a plurality of beads to attenuate unwanted fluid pressure pulses, the plurality of beads being located within at least one cavity of the manifold or within at least one of the plurality of fluid conduits.

[0094] Embodiments of the method include passively attenuating or otherwise reducing pressure pulses that occur due to the opening and closing of channels in the fluid system of the valve and the channels in the valve itself. Also contemplated embodiments include methods of expanding a flexible fluid conduit in response to pressure pulses generated by the opening and closing of the valve. The method includes not utilizing or dynamically damping an active or powered device, but attenuating fluid pressure pulses via a passive damping system that is configured to automatically attenuate pressure pulses felt upstream of the gradient proportional valve. Thus, the contemplated method includes improving composition accuracy across the entire solvent composition range.

[0095] Although the present invention has been shown and described with reference to particular embodiments, it will be understood by those skilled in the art that various changes in form and details may be made without departing from the spirit and scope of the invention as recited in the appended claims. In addition, although various embodiments of the passive form of fluid damping of pressure pulses have been described in detail, these embodiments may be employed consistently or incorporated into a single gradient proportional valve in combination with some or all of the features described herein. In addition, the passive form of fluid damping of pressure pulses may be supplemented in combination with one or more active forms that require a power source and / or control system to function.

Claims

1. A gradient proportional valve for liquid chromatography, the gradient proportional valve comprising: a plurality of inlet ports configured to receive a plurality of fluids; multiple actuation mechanisms; a manifold connected to each of the plurality of inlet ports, configured to mix the plurality of fluids in a controlled manner to provide a fluid composition, the manifold comprising a plurality of fluid conduits within the manifold, each of the plurality of conduits receiving a fluid through a corresponding one of the plurality of inlet ports, each of the plurality of fluid conduits being in operative communication with a corresponding one of the plurality of actuation mechanisms, the plurality of actuation mechanisms being configured to open and close each of the plurality of fluid conduits in a controlled manner; a common outlet port configured to receive the fluid composition; as well as A passive fluid damping system configured to attenuate unwanted fluid pressure pulses in the manifold, wherein the passive fluid damping system includes at least one of the plurality of fluid conduits, wherein at least one of the plurality of fluid conduits includes a flexible fluid conduit having an entire wall made of a flexible material.

2. The gradient proportional valve according to claim 1, wherein: Each of the plurality of fluid conduits includes the flexible fluid conduit.

3. The gradient proportional valve according to claim 1, wherein: The flexible fluid conduit is made of a material selected from the group consisting of polytetrafluoroethylene (PTFE), fluorinated ethylene propylene (FEP), and perfluoroelastomer (FFKM).

4. The gradient proportional valve according to claim 1, further comprising: A plurality of respective actuation mechanisms, wherein each of the plurality of respective actuation mechanisms is a solenoid valve, and wherein the flexible fluid conduit of at least one of the plurality of fluid conduits is located upstream of one of the solenoid valves.

5. The gradient proportional valve of claim 1 , further comprising a single accumulator chamber inside the manifold, wherein each of the plurality of fluid conduits provides fluid to the single accumulator chamber, wherein the single accumulator chamber comprises a diaphragm disposed in the single accumulator chamber, a first side of the diaphragm being exposed to the interior of the single accumulator chamber, and a second side of the diaphragm being exposed to the exterior of the manifold.

6. The gradient proportional valve of claim 1, further comprising a plurality of modular receiver ports within the manifold, each of the plurality of receiver ports being in fluid communication with a corresponding one of the plurality of fluid conduits.

7. The gradient proportional valve of claim 6, further comprising at least one modular flat bottom mounting plug received in the receiving port, the flat bottom being exposed to the received fluid from a corresponding one of the plurality of fluid conduits.

8. The gradient proportional valve according to claim 6 further comprises at least one modular diaphragm assembly plug received in the receiving port, the diaphragm assembly plug producing an accumulator chamber inside the manifold that is fluidically connected to a corresponding one of the plurality of fluid conduits.

9. The gradient proportional valve of claim 1, further comprising at least one accumulator chamber within the manifold, wherein at least one of the plurality of fluid conduits provides fluid to the at least one accumulator chamber, wherein: The passive fluid damping system includes the at least one accumulator chamber of a ribbed diaphragm disposed in the passive fluid damping system.

10. The gradient proportional valve according to claim 1, wherein: The passive fluid damping system includes at least one of the respective actuation mechanisms having a flexible seal made of at least one of PTFE, FEP, and FFKM.

11. The gradient proportional valve according to claim 1, wherein: The passive fluid damping system includes at least one of the plurality of fluid conduits including a curved pulse damping flow geometry configured to mitigate fluid pressure pulses.

12. The gradient proportional valve according to claim 1, wherein: The passive fluid damping system includes a plurality of beads positioned within at least one cavity in the manifold or within at least one of the plurality of fluid conduits, the plurality of beads configured to reduce pulse amplitude.

13. A method for mixing fluids in liquid chromatography, the method comprising: Provide gradient proportional valve; receiving a plurality of fluids in a plurality of inlet ports of the gradient proportioning valve; mixing the plurality of fluids in a controlled manner within a manifold of the gradient proportioning valve to provide a fluid composition, the manifold comprising a plurality of fluid conduits within the manifold, wherein at least one of the plurality of fluid conduits is a flexible fluid conduit having an entire wall made of a flexible material; opening and closing each of the plurality of fluid conduits in a controlled manner; outputting the fluid composition from a common outlet port of the gradient proportioning valve; as well as Unwanted fluid pressure pulses in the manifold are attenuated using the flexible fluid conduit.

14. The method according to claim 13, wherein: The controlled opening and closing of each of the plurality of fluid conduits is performed by a corresponding solenoid valve, the method further comprising: Unwanted fluid pressure pulses generated by the opening and closing of at least one of the corresponding solenoid valves are absorbed using the flexible fluid conduit upstream of the at least one of the corresponding solenoid valves.

15. The method according to claim 13, wherein: Each of the plurality of fluid conduits is a flexible fluid conduit, and the method further includes attenuating the unwanted fluid pressure pulses in the manifold using each of the plurality of flexible fluid conduits.

16. The method according to claim 13, further comprising: A single accumulator chamber having a diaphragm disposed therein is utilized to attenuate unwanted fluid pressure pulses in the manifold.

17. The method according to claim 13, further comprising: The unwanted fluid pressure pulses are attenuated using a flexible seal made of at least one of PTFE, FEP and FFKM.

18. The method according to claim 13, further comprising: The unwanted fluid pressure pulses are mitigated using tortuous flow geometry within the manifold.

19. The method according to claim 13, further comprising: The unwanted fluid pressure pulses are attenuated using a plurality of beads located within at least one cavity of the manifold or within at least one of the plurality of fluid conduits.

20. A liquid chromatography system, comprising: The gradient proportional valve according to claim 1; syringe; Separation column; as well as Detector.

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