Patent Description:
The invention relates generally to gradient proportioning valves. More particularly, the invention relates to a gradient proportioning valve having passive fluidic dampening features, and associated systems and methods.

Gradient proportioning valves (GPVs) are known for use in low pressure mixing liquid chromatography systems (i.e. quaternary systems). <CIT> describes an exemplary prior art GPV. Specifically, the GPV is responsible in the systems for setting the desired solvent composition. A typical GPV includes multiple solenoid valves mounted on a common manifold that open and close at precise times with respect to the system pump cycle. Upon opening and closing of GPV solenoid valves, pressure pulses are introduced to the system. Pressure pulses are also caused by the start and end of the intake stroke during the pump cycle. Such pressure pulses can cause undesirable oscillations in the compositional error of chromatography systems. These oscillations therefore diminish compositional accuracy and performance of a liquid chromatography system.

<CIT> discloses a further prior art gradient proportioning valve, which comprises a plurality of accumulator chambers, each having a diaphragm disposed therein.

According to the present invention in a first aspect, there is provided a gradient proportioning valve for liquid chromatography as recited by Claim <NUM>.

Further, preferable, features are presented in the dependent claims.

According to another aspects, a method of mixing fluid in liquid chromatography and a liquid chromatography system are provided according to claim <NUM> and claim <NUM> respectively.

A gradient proportioning valve accommodates the flow of fluids from external reservoirs into the valve for mixing in appropriate proportions to form a liquid composition. In an actual embodiment, such a valve may include four inlet valves ported to a common outlet, the embodiment shown hereinbelow in <FIG> shows two inlet valves ported to a common outlet. In terms of functionality, each inlet valve may be a normally closed, solenoid actuated diaphragm valve that is switched in a controlled manner to provide the appropriate amount of fluid required in mixing the liquid composition. The function of the overall valve is to provide a continuous stream of a compositionally accurate mixture of components, such as solvents in a high pressure liquid chromatography (HPLC) implementation. The mixture may be provided from the common outlet under flowing conditions, while not interfering with the flow rate of the fluid input system, and without changing or otherwise affecting the quality / composition of the fluids input for mixing.

Embodiments of the gradient proportioning valve described herein may be configured to passively dampen or otherwise reduce pressure pulses that occur due to the opening and closing of channels in the fluidic systems of the valve, and in the valve itself. Such pressure pulses have been found to cause large, sinusoidal oscillations in compositional error. Passive fluidic dampening may include dampening these fluidic pressure pulses without an active, powered, and/or controlled device. Thus, the gradient proportioning valves described herein may be configured to provide improved compositional accuracy across an entire solvent composition range. This improved compositional accuracy may be particularly important at higher flow rates.

<FIG> is a block diagram of an exemplary liquid chromatography system <NUM>, suitable for preparative- or process-scale liquid chromatography, in accordance with one embodiment of the invention. The system <NUM> is an exemplary system within which gradient proportioning valves may be included according to the embodiments described herein. The apparatus <NUM> includes four solvent reservoirs 1A, 1B, 1C, 1D, a gradient proportioning valve <NUM>, an inlet manifold valve <NUM>, a pump <NUM>, a solvent mixer <NUM>, an injector <NUM>, a separation column <NUM>, a detector <NUM>, and a control unit <NUM>. The gradient proportioning valve <NUM> represents a valve that includes one or more of the dampening features described herein. Thus, the gradient proportioning valve <NUM> may be any of the gradient proportioning valves shown in <FIG> and described herein below.

In operation, the gradient proportioning valve <NUM> and the pump <NUM>, in response to control of the control unit <NUM>, select and draw one or more solvents from the reservoirs 1A, 1B, 1C, 1D. The gradient proportioning valve <NUM> may be operated, in response to control of the control unit <NUM>, to provide a selected solvent composition, which is optionally varied in time, for example, to implement gradient-mode chromatography. The solvent mixer <NUM> is any suitable mixer, including known passive and active mixers. The injector is any suitable injector <NUM>, including known injectors, for injecting a sample into the solvent flow. The injector <NUM> is optionally disposed at alternative locations in the solvent flow path, as will be understood by one having ordinary skill in the liquid-chromatography arts. The inlet manifold valve <NUM> is connected to an outlet tube from the gradient proportioning valve <NUM>, and to two inlet tubes connected to the pump <NUM>, to supply solvent to the two piston chambers. The inlet manifold valve <NUM> optionally includes a sample injector, to inject samples into the solvent prior to its entry into the pump <NUM>. The control unit <NUM> -including, for example, a personal computer or workstation--receives data and/or provides control signals via wired and/or wireless communications to, for example, the gradient-proportioning valve <NUM>, the pump inlet manifold <NUM>, the pump <NUM>, and/or the detector <NUM>. The control unit <NUM> supports, for example, automation of sample processing. The control unit <NUM>, in various illustrative embodiments, is implemented in software, firmware, and/or hardware (e.g., as an application-specific integrated circuit). The control unit <NUM> includes and/or is in communication with storage component(s).

Suitable implantations of the control unit <NUM> include, for example, one or more integrated circuits, such as microprocessors. A single integrated circuit or microprocessor in some alternative embodiments includes the control unit <NUM> and other electronic portions of the apparatus <NUM>. In some embodiments, one or more microprocessors implement software that enables the functions of the control unit <NUM>. In some embodiments, the software is designed to run on general-purpose equipment and/or specialized processors dedicated to the functionality herein described.

In some implementations of the system <NUM>, the control unit <NUM> includes a user interface to support interaction with the control unit <NUM> and/or other portions of the system <NUM>. For example, the interface is configured to accept control information from a user and to provide information to a user about the system <NUM>. The user interface is used, for example, to set system control parameters and/or to provide diagnostic and troubleshooting information to the user. In one embodiment, the user interface provides networked communication between the system <NUM> and users located either local to the operating environment or remote from the operating environment. The user interface in some implementations is used to modify and update software. In view of the description of illustrative embodiments provided herein, it will be apparent to one having ordinary skill in the separation arts that various other configurations and implementations of control units can be utilized in other embodiments of the invention to provide automated control of process-scale and preparative-scale chromatography.

The pump <NUM> may be configured to provide solvent at pressures of at least <NUM> psi, or <NUM>,<NUM> psi, or <NUM>,<NUM>, psi <NUM>,<NUM> psi or greater. The pump includes any suitable piston-based pump, including known pumps, such as available from Waters Corporation, Milford, Mass. The column <NUM> is any column suitable for process-scale and preparative-scale chromatography. The column contains, for example, any medium suitable for such a purpose, including known media. The sorbent material is selected from any suitable sorbent material, including known materials such as silica or a mixture of silica and a copolymer such as an alkyl compound. The solvents are any solvents suitable to a desired separation process, including known solvents.

Again, the system <NUM> described above is meant to be an exemplary liquid chromatography system in which various embodiments of the gradient proportioning valves may be deployed. However, the gradient proportioning valves described herein may be implemented in any system in which gradient fluid mixing is performed. For example, in a liquid chromatography quaternary system, after the solvent reservoirs 1A, 1B, 1C, <NUM> D, the next component the solvent goes into may be a degasser chamber. From there, the solvent may enter the gradient proportioning valve <NUM>. After the gradient proportioning valve <NUM>, the solvent may then go through a check valve to the pump (i.e. with no inlet manifold valve). Any liquid chromatography system configurations which may deploy a gradient proportioning valve are contemplated for incorporation of the principles described herein.

Referring now to <FIG>, a perspective view of a gradient proportioning valve 2A is shown, in accordance with one embodiment. The gradient proportioning valve 2A includes accumulators 19A, 19B located directly adjacent to switching valves 17A, 17B, on the side closest to the reservoirs 10A, 10B. It should be understood that embodiments of the gradient proportioning valve 2A may include two additional accumulators and switching valves (not shown) located on the two open sides of the gradient proportioning valve 2A, thereby connecting the gradient proportioning valve <NUM> to two additional reservoirs, such as the reservoirs 1C, 1D shown in <FIG>. Each of the accumulators 19A, 19B may include a soft-walled flexible plastic tube <NUM> of generally circular cross-section. As shown, the accumulator tube <NUM> may be adapted at an end closest to the valve inlet to snugly slide over a rigid plastic connector <NUM>. A connecting tube <NUM> may be implemented at the opposite end of the accumulator tube to hold a relatively long length of flow tubing <NUM> that connects the valves with the reservoirs 1A, 1B. The end of the accumulator tube adjacent to the connecting tube may be caused to assume approximately the cross-section of a flattened ellipse <NUM> which may allow a significant internal volume change to occur in the accumulator tube, with little change in pressure thereby allowing the accumulator to overcome the effects of hydraulic inertia.

<FIG> depicts a side cross sectional view of the gradient proportioning valve 2A of <FIG>, in accordance with one embodiment. The gradient proportioning valve 2A includes a valve manifold <NUM> that accommodates the flow of fluids from external reservoirs (not shown). For the sake of clarity of the discussion hereinafter, the illustrative valve described herein has the capacity to mix only two input fluid streams. However, the features described herein may be applied to valves mixing, for example, four or more input fluid streams. The input fluid streams to be mixed are received from the reservoirs and are introduced into the valve at inlet ports <NUM>. Fluids from the respective reservoirs, such as solvents used in HPLC as known in the art, flow into respective inlet ports <NUM> and thereafter flow through respective inlet conduits <NUM> in the manifold <NUM> into respective accumulator volumes or chambers <NUM>.

The integral accumulator chambers <NUM>, as well as the inlet ports <NUM> and inlet conduits <NUM>, are appropriately dimensioned as a function of the flow rate of the valve application. The chamber <NUM> is frustum-shaped having a conical-base opposed to the inlet conduit <NUM>. The chamber is shaped to maximize the surface area of the diaphragm (for compliance), and the inlet conduit <NUM> is positioned to allow for the best swept volume geometry. Accordingly, the chamber <NUM> also has a smooth transition from larger to smaller cross-section. The placement of the chamber is such that the fluidic resistance between a valve diaphragm <NUM> (discussed hereinafter) and the accumulator is minimized. Fluid flowing through the conduit <NUM> flows perpendicular to the conical-base, into the chamber <NUM> to confront the base or back of the chamber <NUM>.

An accumulator diaphragm <NUM> is positioned at the conical-base or back of the chamber <NUM>, opposite the inlet conduit <NUM>. The diaphragm <NUM> in this illustrative embodiment, is a <NUM> inch thick film formed of Polytetrafluoroethylene (PTFE) laminated on each side with Fluorinated Ethylene Propylene (FEP).

The diaphragm, as with all components in the fluid path of the present illustrative embodiment, is formed of materials that are functionally unaffected by a full range of organic solvents and aqueous solutions of acids, bases, salts, surfactants, etc. and other phase modifiers that may be used in any mode of liquid chromatography. The diaphragm <NUM> effects a membrane or compliant member at the back of the accumulator chamber <NUM> to allow internal volume changes in the chamber to occur with little change in pressure. Accordingly, as with the less advantageous accumulator tubes of the prior art, the valve can overcome the effects of hydraulic inertia. The compliance and damping of the diaphragm are optimized for the applications flow characteristics, as will be appreciated by those skilled in the art.

An oversized bore <NUM> behind the back of the conical-base or back of the accumulator chamber <NUM> is configured to receive the diaphragm <NUM> for clamping and sealing the diaphragm tightly therein. A seating surface <NUM> interior to the bore <NUM> provides an abutment against which the diaphragm seats. A sealing groove <NUM> is disposed in the seating surface <NUM> and provides a portion of the single seal effected in the implementation according to the invention. A cylindrical sealing plug <NUM> formed of stainless steel, includes a sealing ridge <NUM> that fits tightly into the sealing groove <NUM> to seal the diaphragm in the bore <NUM> when the plug <NUM> is engaged against the seating surface <NUM> with the diaphragm sandwiched therebetween.

Preferably, the sealing plug <NUM> is dimensioned to fit snugly, yet slidably within the bore <NUM>. The plug <NUM> is held in place by a clamping plate <NUM> which is mechanically attached to the valve manifold such as by a screw <NUM>. Additional mounting holes <NUM> are provided in the clamping plate <NUM> to facilitate the mechanical fastening of the clamping plate to the valve manifold <NUM>. In this illustrative embodiment, resilient members such as belleville springs <NUM> or washers are disposed between the sealing plug <NUM> and the clamping plate <NUM>, to provide some resiliency.

The diaphragm according to the invention overcomes hydraulic inertia while minimizing the volume of fluid in the valve that is exposed to potential air permeation, by limiting the surface area of the diaphragm that is exposed to ambient air. In contrast to the prior art wherein the entirety of the accumulator tubes were exposed and the volumes of fluid therethrough subjected to ambient air permeating the tubes, the diaphragm according to the present invention is only exposed to ambient in a limited manner. Atmospheric ports <NUM> are provided in the clamping plate <NUM> to permit ambient air at the back of the diaphragm <NUM>. While exposure to ambient air is necessary for the diaphragm to perform its intended function, the reduced surface area exposed within the atmospheric ports significantly limits permeation of air through the diaphragm.

As briefly described hereinbefore, input fluid streams to be mixed are received from reservoirs and are introduced into the valve manifold <NUM> at inlet ports <NUM>. Fluids from the respective reservoirs flow into respective inlet ports <NUM> and thereafter flow through respective inlet conduits <NUM> in the manifold <NUM> into respective accumulator volumes or chambers <NUM>. The inlet conduits <NUM> may be internal to the housing of the gradient proportioning valve 2A, and may be compliant conduits made of a compliant material, as described in more detail herein below. Thus, the inlet conduits <NUM> may be configured to expand or contract as a result of internal fluid pressure therein.

In the respective integral accumulator chambers <NUM> the fluids to be mixed encounter the compliant diaphragm which allows internal volume changes in the chambers to occur with little change in pressure so that the valve can overcome the effects of hydraulic inertia. The fluids to be mixed flow out of the chambers <NUM> through chamber ports <NUM> whereupon the fluids are available at switched valve diaphragms <NUM>. The chamber ports <NUM> may be compliant fluidic conduits internal to the housing or outer body of the gradient proportioning valve 2A. The chamber ports <NUM> may be configured to expand or contract depending on the fluidic pressure of the fluid therein. The valve diaphragms are reciprocated by switched valves as known in the art. The controlled switching of the valve diaphragms determines the proportion of a respective fluid that is received in a common port <NUM> within the valve manifold <NUM>. The respective fluids are mixed in their respective proportions in the common port <NUM> and are available at an outlet port <NUM> for downstream processing as known in the art. Similar to the camber ports <NUM> and the inlet conduits <NUM>, the common port <NUM> may be located internal to the housing or body of the gradient proportioning valve 2A and may be a compliant fluidic conduit that is configured to expand or contract with changes to fluidic pressure therein. The compliance of the chamber ports <NUM> and or inlet conduits <NUM> and/or common ports <NUM> may comprise a passive fluidic dampening system configured to dampen fluidic pressure pulses as described herein.

Although only a two input valve is described in the illustrative embodiment herein, it will be appreciated that the concepts according to the invention could be implemented in a valve having any number of inlet ports for mixing a liquid composition.

While the diaphragm described herein is formed of FEP-PTFE-FEP laminated, it will be appreciated that other materials can be implemented to effect a diaphragm, such as thin stainless steel, various composite materials, rubber or the like.

Although the sealing plug in the illustrative embodiment is a cylindrical plug formed of stainless steel, it will be appreciated that alternative sealing mechanisms can be implemented while permitting ambient pressure at the back of the diaphragm, such as spongy materials, cylindrically shaped composite material or the like. Furthermore, while the sealing plug effects a tight seal by having a sealing ridge that seats in a sealing groove in a bore receiving the plug, it will be appreciated that the groove could be in the plug and the ridge on a surface of the bore.

The gradient proportioning valve 2A thus includes a passive fluidic dampening system including one or more dampening mechanisms, systems or methods, configured to passively dampen unwanted fluidic pressure pulses in the manifold. Thus, the gradient proportioning valve 2A may be configured to dampen or otherwise reduce pressure pulses that occur due to the opening and closing of channels in the fluidic systems associated with the valve 2A, and within the valve 2A itself. In particular, the fluidic dampening system may be configured to passively dampen the unwanted fluidic pressure pulses created by the solenoid valves 17A, 17B of the valve 2A. The gradient proportioning valve 2A may thereby be configured to provide improved compositional accuracy across an entire solvent composition range.

In one or more embodiments, the fluidic dampening system includes at least one of the plurality of fluid conduits including a compliant portion. For example, any of the inlet conduits <NUM>, the chamber ports <NUM> and/or the common port <NUM> may be made of a compliant material so that fluid passes directly through a channel or conduit made of a compliant material. Compliance herein may include materials such as Polytetrafluoroethylene (PTFE), Flourinated Ethylene Propylene (FEP) or perfluoroelastomer (FFKM) or materials having similar Young's Modulus'. Compliance herein defines materials that undergo elastic deformation due to force or pressure at the pressures experienced by a liquid chromatography system. Thus, compliant materials in the valves herein may flex when force is applied, but return to its original shape undeformed after the force is halted. Compliance may further allow the channels <NUM>, <NUM>, <NUM> to expand with increased pressure, and contract with reduced pressure. The complaint materials herein may be configured to achieve force and motion transmission through elastic body deformation from the pressure of the internal fluid within the conduit. Thus, when force or pressure occurs within the conduits, the compliance of the material will cause the channel to undergo elastic body deformation, which does not cause permanent or plastic deformation. When the force or pressure is thereby reduced, the conduits may be configured to return to their original form.

The compliance of the channels described herein, including that in one or more of the channels <NUM>, <NUM>, <NUM>, may be configured to undergo this elastic body deformation under pressure ranges found within those channels of the GPV. Operating pressure ranges in the GPV may be between -<NUM> to <NUM> pounds per square inch (psi). Pressure pulses from valve actuation may be, for example, <NUM> psi or less. In exemplary embodiments, the settling time after a pressure pulse may be less than one second. In other embodiments, the operating pressure ranges of a GPV may be narrowed, for example, between <NUM> psi to - <NUM> psi. Likewise, the pressure pulses may be even less than <NUM> psi, for example, may take the form of about <NUM> psi or about <NUM> psi. The settling time may also be less than a second; for example. <NUM> seconds or. <NUM> seconds.

Still further, exemplary compliances of the compliant channels <NUM>, <NUM>, <NUM> are contemplated. In one embodiment, the compliant channels <NUM>, <NUM>, <NUM> may have a compliance greater than. <NUM>µL / psi (e.g. for every psi increase in pressure, the channel may expand to accommodate. <NUM> greater µL or more). In some embodiments compliance may be at least. <NUM>µL / psi, at least. <NUM>µL / psi, or at least <NUM>µL / psi.

Thus, the compliance of the channel may act as a fluidic capacitor that dampens pulsations in the system. While a compliant fluidic conduit may be applied to the embodiment shown in <FIG>, compliant fluidic conduits within the valve may be included on any of the valve embodiments described herein. Any contemplated gradient proportioning valve configuration consistent with the embodiments described herein may include compliant fluidic conduits.

Still further, in one or more embodiments, the fluidic dampening system includes at least one of the respective actuation mechanisms having a compliant seal, for example made of a compliant material such as PTFE, FEP or FFKM. For example, in the embodiment shown in <FIG>, a conical sealing poppet (not shown) that seals off channel <NUM> at the solenoid switched valve diaphragm <NUM> (as known the art of solenoid valves) may be replaced or modified with a more compliant material. In one embodiment, a secondary seal may surround or otherwise modify the conical sealing poppet to absorb pulses upon opening and/or closing of the solenoid seal.

<FIG> depicts a schematic view of a gradient proportioning valve 2B having compliant fluidic conduits <NUM>, <NUM>, in accordance with one embodiment. The gradient proportioning valve 2B is shown including four inlet ports <NUM>. Each respective inlet port <NUM> provides fluid through a complaint fluid conduit <NUM>. The respective compliant fluid conduits <NUM> are configured to provide fluid from the respective inlet ports <NUM> to respective solenoid valves <NUM>. The respective solenoid valves <NUM> thereafter provide fluid to another respective compliant fluid conduit <NUM>. From the compliant fluid conduits <NUM>, the fluid may then converge into a single outlet port <NUM>. A single converged fluid conduit may also be provided prior to the single outlet port <NUM>, which may also be made of a compliant material. The compliant fluid conduits <NUM> and the compliant fluid conduits <NUM> may each be made of the same materials described hereinabove with respect to the inlet conduits <NUM>, the chamber ports <NUM> and/or the common port <NUM>.

Unlike <FIG>, in this embodiment sufficient pressure dampening may be provided by the compliant material in the passive fluidic dampening system by some or all of the fluidic conduits within the valve 2B such that the accumulator chambers <NUM> is not be unnecessary. Further, in other embodiments, it may be possible that some but not all of the various fluid conduits internal to the housing of the gradient proportioning valve 2B are compliant. For example, only the fluid conduits <NUM> located downstream from the solenoid valves <NUM> may be compliant, while the upstream conduits <NUM> connecting the inlet <NUM> with the solenoid valves <NUM> may be made from a typical fluidic channel material that is non-flexible and non-expanding under the pressures of the system. Alternatively, only the fluid conduits upstream from the solenoid valves may be compliant.

In some embodiments, the compliant conduits may be particularly effective upstream of the solenoid valves. There, the compliant conduits may be configured to mitigate the pressure pulses, act as flow buffers, and improve response time. In other embodiments, compliant conduits could be located after the solenoid valves, but before the mixing point in the GPV. Whatever the embodiment, the complaint conduits are located before the mixing point of the GPV. After the mixing point, the compliant conduits might negatively impact the solvent metering. In some embodiments, the entirety of a conduit may be made of the compliant material. According to the invention an entire wall(s) of the fluidic channel is made from the compliant material such that the pulse dampening feature is in-line with the flow rather than having the enter a separate accumulator chamber.

<FIG> depicts a schematic view of a gradient proportioning valve 2C having a manifold <NUM> which may include the same or similar features to the manifold <NUM> but may have four inlet ports <NUM> for combining with a single outlet port <NUM>, in accordance with one embodiment. Each inlet port <NUM> is connected to a respective accumulator chamber <NUM> via a respective inlet conduit <NUM>. As shown, the accumulator chambers may be attached or otherwise connected to the manifold <NUM> via a compression plate <NUM>. Chamber ports <NUM> connect the respective accumulator chambers <NUM> to solenoid valves 117A, 117B, 117C, 117D and their respective switched valve diaphragms <NUM>. After passing the switched valve diaphragms <NUM> of the respective solenoid valves 117A, 117B, 117C, 117D, fluids are received in ports <NUM> which combine prior to the outlet port <NUM> for downstream processing.

In one or more embodiments, the fluidic dampening system includes a plurality of beads located within at least one chamber, such as the integral accumulator chambers <NUM> within the manifold <NUM>. The plurality of beads may be spherical in shape, or may each be any round shaped object configured to reduce pulse amplitude of fluidic pressure pulses. The plurality of beads may additionally or alternatively be located within any of the fluidic conduits within the manifold <NUM>, such as the inlet conduits <NUM> and/or the chamber ports <NUM> and/or the common port <NUM>. The plurality of beads may be disposed within the manifold <NUM> such that they occupy the volume of whatever space they inhabit, such that the plurality of beads do not move significantly with respect to the manifold <NUM> as the manifold <NUM> is moved, shaken, or otherwise subjected to force.

In some embodiments, the plurality of beads may be disposed within each fluidic path (i.e. the path from one of the inlet ports <NUM> to the outlet port <NUM>) at the same location and in the same manner (number of beads, size of beads, etc). In other embodiments, each respective fluidic path may include its own bead configuration. For example, a first fluidic path coming from a first inlet port may include a plurality of beads of a first diameter in accumulator chamber <NUM> of the first fluidic path. A second fluidic path may include no beads, while a third and a fourth fluidic path may include beads of a different diameter in their accumulator chambers <NUM>. The fluidic dampening system may include any type of beads, any size of beads, any material of beads, any amount of beads, disposed at any location, for any given fluidic path. While the plurality of beads has been described with reference to <FIG>, the plurality of beads described herein may be utilized in combination with any of the other gradient proportioning valve embodiments described herein, or combinations thereof.

Referring now to <FIG>, a side cross sectional view of a solenoid valve 117E is shown having an energy absorbing solenoid armature stop <NUM>, in accordance with one embodiment. The solenoid valve 117E includes a solenoid <NUM> surrounding an armature <NUM>. The armature <NUM> is disposed within a chamber <NUM> surrounding the armature <NUM>. A spring mechanism <NUM> is located at an end of the chamber <NUM>. When the solenoid <NUM> is activated, the armature <NUM> is configured to move toward the energy absorbing armature stop <NUM> to open the valve 117E and allow fluid to move through the valve 117E from a fluidic inlet <NUM> to a fluidic outlet <NUM>. In this embodiment, the fluidic dampening system of a contemplated gradient proportioning valve, such as the valve 2A or 2B, includes the energy absorbing solenoid armature stop <NUM> located at an end of where the armature <NUM> would otherwise contact when the valve is in an open state. The energy absorbing armature stop <NUM> may be a deformable or compliant material configured to dampen the hard stop of the armature <NUM> against the wall of the chamber <NUM> when the spring mechanism <NUM> is compressed. The solenoid armature stop <NUM> may be made of any polymeric, elastomeric, or composite material, such as, but not limited to urethane, FFKM, silicon, or the like. It should be understood that one or more of the solenoid valves 117E may be used in any of the gradient proportioning valves described herein.

<FIG> depicts a schematic view of another gradient proportioning valve 2D having a single accumulator chamber <NUM>, in accordance with one embodiment. The gradient proportioning valve 2D includes a manifold <NUM> having four inlet ports <NUM>, each connected to a respective solenoid valve <NUM> through respective inlet conduits <NUM>. The solenoid valves <NUM> each include a port <NUM> that transfers fluid to the single accumulator chamber <NUM>. The single accumulator chamber <NUM> includes a diaphragm disposed therein. Like the accumulator chambers <NUM> shown in <FIG>, a first side of the diaphragm may be exposed to an interior of the single accumulator chamber <NUM> while a second side of the diaphragm may be exposed to an exterior of the manifold <NUM>. The single accumulator chamber <NUM> may thereby be a compliant chamber and may be located before, after, or at a mixing point of the four fluidic paths. In one embodiment, the entirety of the accumulator chamber <NUM> may include compliant walls in addition or alternatively to the compliant diaphragm disposed therein. Further, a plurality of beads may be located in the single accumulator chamber, as described above.

<FIG> depicts a side cross sectional view of a portion of a modular gradient proportioning valve 2E, in accordance with one embodiment. The modular gradient proportioning valve 2E includes an inlet port <NUM>, fluidically connected to a modular receiver port <NUM>. A chamber port <NUM> extends from the modular receiver port <NUM> to a solenoid diaphragm <NUM>. A common port <NUM> extends from the solenoid diaphragm <NUM> to a mixing point after which the fluidic pathway extends to an outlet <NUM>. The modular gradient proportioning valve 2E includes the modular receiver port <NUM> internal to the manifold <NUM>. While a single of the modular receiver ports <NUM> are shown, it should be understood that two, three, four or more separate modular receiver ports <NUM> may be included - one for each fluidic pathway. In other embodiments, a plurality of modular receiver ports <NUM> may be included within each separate fluidic pathway. Each of the plurality of receiving ports may be configured to be in fluidic communication with one of the fluidic pathways or conduits within the manifold <NUM>. The modular receiver ports <NUM> may be threaded, for example, to allow for easy removal or attachment of modular fitting plugs. Different fitting plugs may be attached to the same manifold <NUM>, or fitting plugs may be removed or added to the manifold as needed depending on the implementation.

<FIG> show two exemplary modular fitting plugs. <FIG> depicts a side cross sectional view of a flat bottom fitting plug <NUM> having a flat bottom <NUM> for incorporation into the modular gradient proportioning valve 2E of <FIG>, in accordance with one embodiment. The flat bottom fitting plug may be receivable in the modular receiving port <NUM> and may include, for example, threads or another attachment mechanism for integrating, attaching, connecting or otherwise coupling to the modular receiving port <NUM>. When inserted and attached within the receiving port <NUM>, the flat bottom <NUM> of the flat bottom fitting plug <NUM> may be exposed to the fluidic pathway but may block fluid from entering into the area occupied by the modular receiving port <NUM>. This creates a bypass in the event that it is unnecessary, for example, to damp pressure pulses in a given fluidic pathway within the manifold.

<FIG> depicts a side cross sectional view of a diaphragm fitting plug <NUM> having a diaphragm <NUM> for incorporation into the modular gradient proportioning valve 2E of <FIG>, in accordance with one embodiment. The modular diaphragm fitting plug <NUM> may be receivable in the modular receiving port <NUM> and may include, for example, threads or another attachment mechanism for integrating, attaching, connecting or otherwise coupling to the modular receiving port <NUM>. The diaphragm fitting plug <NUM> may be configured to create an accumulator chamber, including the same or similar structure to the accumulator chambers <NUM> described hereinabove, internal to the manifold <NUM> in fluidic communication with the respective one of the fluidic pathways and/or fluidic conduits.

Using any combination of diaphragm fitting plugs <NUM> and flat bottom fitting plugs <NUM>, the modular gradient proportioning valve 2E may be configured to interchangeably receive various fitting plugs for creating a customizable valve manifold depending on the particular implementation needed. It is further contemplated that different types of diaphragm fittings are contemplated having different characteristics - some may include more compliant or less compliant diaphragms, some may or may not include a beaded chamber, or the like. Various modular combinations are contemplated.

<FIG> depicts a top view of a ribbed diaphragm <NUM> for a gradient proportioning valve, in accordance with one embodiment. <FIG> depicts a side view of the ribbed diaphragm <NUM> of <FIG>, in accordance with one embodiment. The ribbed diaphragm <NUM> includes a geometry that includes a number of concentric ribs defining an interior circumference <NUM>, a first concentric ring <NUM>, a second concentric ring <NUM>, and a third concentric ring <NUM>. As shown in <FIG>, the concentric rings get increasingly deeper as the diaphragm <NUM> approaches the center. The ribs in the diaphragm (where the concentric portions <NUM>, <NUM>, <NUM>, <NUM> meet) may be flexible such that the diaphragm deepens when subjected to pressure from one side. The ribs may be configured to provide further compliance to the diaphragm <NUM> while still maintaining a compact form. The compliance of the ribbed diaphragm may be configured to dampen pressure pulses. The ribbed diaphragm <NUM> may be utilized on any diaphragm within any of the gradient proportioning valves described herein and/or manifolds thereof.

<FIG> depicts a side view of a diffusion bonded gradient proportioning valve 2F, in accordance with one embodiment. In this embodiment, the gradient proportioning valve and/or manifold thereof includes at two portions that are diffusion bonded together - a top manifold portion 610A and a bottom manifold portion 610B. By creating two separate manifold portions 610A, 610B and diffusing those portions together, different internal geometries can be achieved that would not be machinable using traditional methods using a single block. The valve 2F is shown including three separate solenoid valves 617A, 617B, 617C, although a forth valve (not shown) is hidden on the opposing surface of the manifold. Three separate fluidic inlets 619A, 619B, 619C are shown, although a fourth inlet and an outlet are both hidden behind the first inlet 618A in this side view.

<FIG> depicts a top cutaway view of the diffusion bonded gradient proportioning valve 2F of <FIG> taken at arrows 10B, in accordance with one embodiment. As shown, in this embodiment, the gradient proportioning valve 2F includes fluidic conduits <NUM> that are bent to create a pulse dampening flow geometry configured to reduce fluidic pressure pulses. In particular, each of the fluidic conduits <NUM> extends from the respective solenoid valves 617A, 617B, 617C, 617D to a mixing point <NUM>.

These fluid conduits <NUM> each include a first bend <NUM> that causes the fluid conduit <NUM> to depart from a direct line toward the mixing point <NUM>. This bend may be at an angle that is greater than <NUM> degrees but less than <NUM> degrees. A second bend <NUM> may be an equal bend in the opposite direction as the first bend <NUM>. A third bend <NUM> is also equal in degree to the first two bends <NUM>, <NUM> and may bend the fluid conduit in the same direction as the second bend <NUM>. The fourth and fifth bends <NUM>, <NUM> may each bend the fluid conduit in the same direction as the first bend <NUM>, while the sixth and final bend <NUM> may bend the fluid conduit back toward the mixing point <NUM> in the same direction as the second and third bends <NUM>, <NUM>. Each of the bends <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> may be at the same angle. The geometry created by the bends in the fluid conduits <NUM> may be configured to prevent pressure pulses caused by the opening and closing of the solenoid valves 617A, 617B, 617C, 617D to reach the mixing point <NUM>. It should be understood that embodiments contemplated may include any bent flow geometry including any number of bends for each of the respective fluidic paths. In some embodiments, different fluid paths from each of the solenoid valves 617A, 617B, 617C, 617D may have differently shaped bends (or no bends at all) depending on the necessary implementation.

Embodiments of the invention further contemplate methods of mixing fluid using the principles described herein above. Methods of mixing fluid may first include providing a gradient proportioning valve consistent with one or more of the principles described herein and/or a liquid chromatography system having such a gradient proportioning valve. Methods may include receiving a plurality of fluids in a plurality of inlet ports of the gradient proportioning valve and mixing the plurality of fluids in a controlled manner within a manifold of the gradient proportioning valve to provide a fluid composition, the manifold including a plurality of conduits. Methods may include opening and closing each of the plurality of conduits in a controlled manner and outputting the fluid composition from a common outlet port of the gradient proportioning valve.

Methods according to the invention include dampening unwanted fluidic pressure pulses in the manifold with a passive fluidic dampening system.

In some embodiments, the opening and closing each of the plurality of fluid conduits in a controlled manner is performed by a respective solenoid valve, and the method further includes absorbing unwanted fluidic pressure pulses created by the opening and closing of the solenoid valve with an energy absorbing solenoid armature stop located in at least one of the respective solenoid valves.

According to the invention, methods include dampening the unwanted fluidic pressure pulses in the manifold with at least one compliant fluid conduit.

In some embodiments, methods may further include dampening unwanted fluidic pressure pulses in the manifold with a single accumulator chamber having a diaphragm disposed therein.

In some embodiments, methods may include removably inserting a plurality of modular fitting plugs into a plurality of respective modular receiving ports of the gradient proportioning valve, and dampening the unwanted fluidic pressure pulses in the manifold with at least one of the plurality of modular fitting plugs.

In some embodiments, methods may further include dampening the unwanted fluidic pressure pulses in the manifold with a ribbed diaphragm. In some embodiments, methods may further include dampening the unwanted fluidic pressure pulses with a compliant seal made of at least one of PTFE, FEP and FFKM.

In some embodiments, methods may further include using a bent flow geometry within the manifold to mitigate the unwanted fluidic pressure pulses.

In still other embodiments, methods may further include dampening the unwanted fluidic pressure pulses with a plurality of beads located within at least one chamber of the manifold, or within at least one of the plurality of fluid conduits.

According to the invention, the method of mixing fluid includes providing a gradient proportioning valve according to claim <NUM>. According to some embodiments, all of the plurality of fluid conduits are compliant fluid conduits. The method further includes 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 dampening the unwanted fluidic pressure pulses in the manifold with the compliant fluid conduit(s). In some embodiments, the opening and closing each of the plurality of fluid conduits in a controlled manner is performed by a respective solenoid valve, such that the method includes absorbing unwanted fluidic pressure pulses created by the opening and closing of at least one of the respective solenoid valves with the compliant fluid conduit located upstream from the at least one of the respective solenoid valves. Still further, the method may further include dampening unwanted fluidic pressure pulses in the manifold with a single accumulator chamber having a diaphragm disposed therein. The method may also further include dampening the unwanted fluidic pressure pulses with a compliant seal made of at least one of PTFE, FEP and FFKM. The method may further include using a bent flow geometry within the manifold to mitigate the unwanted fluidic pressure pulses. Further, the method may further include dampening the unwanted fluidic pressure pulses with a plurality of beads located within at least one chamber of the manifold, or within at least one of the plurality of fluid conduits.

Embodiments of methods include passively dampening or otherwise reducing pressure pulses that occur due to the opening and closing of channels in the fluidic systems of the valve, and in the valve itself. Embodiments also contemplated further include methods of expanding a compliant fluid conduit in response to a pressure pulse created by the opening and closing of a valve. Methods include dampening fluidic pressure pulses without an active, or powered dampening device, but rather via passive dampening systems which are configured to automatically dampen pressure pulses from being felt upstream from the gradient proportioning valve. Thus, methods contemplated include improving compositional accuracy across an entire solvent composition range.

Claim 1:
A gradient proportioning valve (2A, 2B) for liquid chromatography comprising:
a plurality of inlet ports (<NUM>, <NUM>) configured to receive a plurality of fluids;
a plurality of actuation mechanisms (17A, 17B, <NUM>);
a manifold (<NUM>) 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 (<NUM>, <NUM>, <NUM>) internal to the manifold, each of the plurality of fluid conduits receiving fluid through a respective one of the plurality of inlet ports, each of the plurality of fluid conduits operatively communicable to a respective one of the actuation mechanisms, the actuation mechanisms configured to open and close each of the plurality of fluid conduits in a controlled manner;
a common outlet port (<NUM>, <NUM>) configured to receive the fluid composition; and
a passive fluidic dampening system configured to dampen unwanted fluidic pressure pulses in the manifold, wherein the passive fluidic dampening system includes at least one of the plurality of fluid conduits comprising a compliant fluid conduit having an entire wall in line with fluid flow being made of a complaint material.