Patent Description:
The invention relates generally to gradient proportioning valves. More particularly, the invention relates to a gradient proportioning valve having dampening features, an associated liquid chromatography system and an associated method of mixing fluid.

In liquid chromatography, solvent managers are used to deliver the mobile phase solvent to the rest of the instrument stack at very precise flow rates, pressures, and solvent compositions. In one example, quaternary solvent managers (QSMs) are a type of solvent manager that meters and mixes the solvents at low pressure before pressurizing and delivering the solvents to the rest of the instrument stack. Metering of the solvents at low pressure is commonly performed by a gradient proportioning valve (GPV).

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.

Typical GPVs utilize compliant diaphragms or poppets to form a seal when toggling the inlet channels open and closed. Upon each actuation, undesirable pressure pulses are generated by the valve and are introduced to the solvent. These pressure pulses cause errors in solvent metering by the GPV, and therefore can impact compositional accuracy and users' chromatography methods. Some GPV designs utilize accumulator diaphragms upstream of each inlet channel to mitigate the pressure pulses introduced by the valve actuation. While these accumulator chambers improve performance, they are costly, require significant space in the manifold, and limit design freedom. There also may be a limit to the effectiveness of accumulator chambers as flow rate increases. <CIT> discloses a pumping process and system for mixing liquids. <CIT> discloses a piston pumping system delivering fluids with a substantially constant flow rate. <CIT> discloses a pump with wash flow path for washing displacement piston and seal.

Therefore, an improved GPV that reduces or dampens undesirable pressure pulses would be well received in the art.

In one embodiment, a gradient proportioning 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 configured to mix the plurality of fluids in a controlled manner to provide a fluid composition, the manifold including a plurality of conduits internal to the manifold, the plurality of inlet ports each configured to provide fluid to a respective one of the plurality of conduits of the manifold; an actuation mechanism having a piston located within a bored structure surrounding the piston, the actuation mechanism configured to open and close at least one of the plurality of conduits in a controlled manner wherein the piston and the bored structure have a tight tolerance configured to create a fluid tight seal when the actuation mechanism closes the at least one of the plurality of conduits; a common outlet port configured to receive the fluid composition; and at least one accumulator chamber located downstream from at least one of the plurality of inlet ports and upstream from the actuation mechanism and the common outlet port, the at least one accumulator chamber having a compliant diaphragm disposed in a back of the at least one accumulator chamber.

Additionally or alternatively, the gradient proportioning valve further includes a separate actuation mechanism for each of the respective plurality of conduits, each of the separate actuation mechanisms having a piston located within a bore with a tight tolerance configured to create a fluid tight seal.

Additionally or alternatively, the piston and the bored structure create the fluid tight seal without a deformable sealing element.

Additionally or alternatively, the actuation mechanism is a solenoid valve.

Additionally or alternatively, the piston is made of ceramic.

Additionally or alternatively, the actuation mechanism is configured to open and close two or more of the plurality of conduits.

Additionally or alternatively, the piston is configured to rotate about the bored structure to open and close the at least one of the plurality of conduits in the controlled manner.

Additionally or alternatively, the piston is configured to rotate less than <NUM> degrees to open and close the at least one of the plurality of conduits in the controlled manner.

Additionally or alternatively, the piston includes a flat surface keyed into one side.

Additionally or alternatively, the piston extends axially along a length, wherein the piston includes a hole extending axially within the piston configured to receive and outlet the fluid from the piston.

Additionally or alternatively, the tight tolerance creates a clearance of <NUM> microns or less between the piston and the bored structure.

Additionally or alternatively, the piston is configured to move axially within the bored structure to open and close the at least one of the plurality of conduits in the controlled manner.

Additionally or alternatively, the piston is configured to move axially and rotate relative the bored structure.

In another embodiment, a method of mixing fluid includes providing a gradient proportioning valve including a manifold having a plurality of conduits; receiving a plurality of fluids in a plurality of inlet ports of the gradient proportioning valve; opening and closing each of a plurality of conduits in a controlled manner with an actuation mechanism having a piston located within a bored structure surrounding the piston; maintaining a fluid tight seal between the piston and the bored structure during the opening and closing; mixing the plurality of fluids in a controlled manner within the manifold of the gradient proportioning valve; and outputting the fluid composition from a common outlet port of the gradient proportioning valve.

Additionally or alternatively, the method further includes preventing unwanted fluidic pressure pulses in the manifold with the actuation mechanism through the minimization of internal fluid volumes within the piston and the bored structure.

Additionally or alternatively, the actuation mechanism is made of ceramic.

Additionally or alternatively, the method further includes opening, with the actuation mechanism, two or more of the plurality of conduits.

The method further includes rotating the piston about the bored structure to open and close the at least one of the plurality of conduits in the controlled manner.

Additionally or alternatively, the method further includes moving the piston axially within the bored structure to open and close the at least one of the plurality of conduits in the controlled manner.

Additionally or alternatively, the method further includes moving the piston both axially and with rotation relative to the bored structure.

In another embodiment, a liquid chromatography system comprises: a gradient proportioning 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 configured to mix the plurality of fluids in a controlled manner to provide a fluid composition, the manifold including a plurality of conduits internal to the manifold, each of the plurality of conduits receiving fluid through a respective one of the plurality of inlet ports; an actuation mechanism having a piston located within a bored structure surrounding the piston, the actuation mechanism configured to open and close at least one of the plurality of conduits in a controlled manner wherein the piston and the bored structure have a tight tolerance configured to create a fluid tight seal when the actuation mechanism closes the at least one of the plurality of conduits; and a common outlet port configured to receive the fluid composition; an injector; a separation column; and a detector.

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 liquid chromatography. The gradient proportioning valves described herein include inlet conduits in communication with one or more inlet valves that may be normally closed. An actuated mechanism may switch open 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 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. 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.

In the embodiments of the gradient proportioning valve described herein, the one or more actuation mechanisms that open and close the inlet conduits each include a plunger or piston mechanism that operates in conjunction with a bored structure. By manufacturing the plunger and bored structure with very tight tolerances, a seal is formed when the plunger is inserted into the bored structure. Using a high precision dimensioned plunger and bore structures as sealing mechanisms, the gradient proportioning valve reduces or minimizes volumes accumulating therein and results in little or no pressure pulses downstream from the actuation mechanism. As described herein, tight tolerances describe tolerances where clearances between the plunger and bored structure may be less than <NUM> microns. For example, in some embodiments, clearances between the plunger and the bored structure that are between <NUM> to <NUM> microns are contemplated. Such tight tolerances and low clearances may provide for a fluid tight seal without the need for deploying deformable sealing elements or other seals. Further, embodiments herein contemplate the use of ceramic materials for the piston and/or the surrounding bored structure.

<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 that 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>. While the embodiment according to the invention shown in <FIG> includes the accumulator volumes or chambers <NUM>, other embodiments, which are not covered by the present set of claims, may not include accumulator chambers <NUM>. Such embodiments may include an inlet port that provides fluid directly to the switching valves 17A, 17B without first passing through an accumulator chamber.

As shown, 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 the switching valves 17A, 17B 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 <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.

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 may overcome 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. 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 desirable for the diaphragm, the reduced surface area exposed within the atmospheric ports significantly limits permeation of air through the diaphragm.

Thus, in operation the 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 fluids to be mixed flow out of the chambers <NUM> through chamber ports <NUM> whereupon the fluids are available at the switching valves 17A, 17B. The switching valves 17A, 17B operate in accordance to the principles of the invention described herein below. The controlled switching of the switching valves 17A, 17B 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.

Although only a two input valve embodiment is described in <FIG>, 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. Further, while the embodiment described herein includes a single switching valve 17A, 17B per inlet port <NUM>, in other embodiments a single switching valve 17A, 17B may operate to open and close a plurality of inlet ports <NUM>, as described herein below.

<FIG> depicts a schematic view of another gradient proportioning valve 2B, in accordance with one embodiment. The gradient proportioning valve 2B is shown schematically including four separate inlet ports <NUM> which provide fluid via a conduit or channel to an accumulator chamber <NUM>, such as the chamber <NUM> shown in <FIG>. Unlike <FIG>, in the embodiment shown in <FIG> there are four separate accumulator chambers <NUM> to accommodate the four inlet ports <NUM>. Further, downstream from each of the accumulator chambers <NUM> is a separate switching valve 17A, 17B, 17C, 17D. The four switching valves 17A, 17B, 17C, 17D each separately outlet fluid to a downstream mix point <NUM> at which the fluid is combined into a single stream. Downstream from the mix point <NUM> is an outlet <NUM>.

<FIG> shows one example schematic view of the gradient proportioning valve 2B where each inlet channel includes its own valve 17A, 17B, 17C, 17D. Further, the schematic shows one accumulator chamber <NUM> for each inlet port <NUM>. In other embodiments contemplated, no accumulator chamber <NUM> may be needed prior to the mixing valves 17A, 17B, 17C, 17D. In still other embodiments, such as those described hereinbelow, an accumulator chamber and switching valve combination can be configured to receive more than one inlet, such as a single accumulator chamber and switching valve for two or more inlets. However, for the embodiment shown in <FIG> displays situations in which a single actuation mechanism may be used for each inlet port. Such a schematic can be used to describe embodiments consistent with the actuation mechanisms shown in <FIG> and described hereinbelow.

Described hereinbelow are several embodiments contemplated for actuation mechanisms for a switching valve, such as one of the switching valves 17A, 17B, 17C, 17D described above. The embodiments of the actuation mechanisms for switching valves described hereinbelow with respect to <FIG>, <FIG>, <FIG> and <FIG> may be implemented via any switching valve mechanism that is configured to move the piston relative to the bored structure or cylinder. For example, the rotational movements of the piston relative to the bored structure may be actuated by a stepper motor, a servo motor, or any other rotational actuator. Axial movement could be controlled by a solenoid, voice coil, piezoelectric actuator, or any other axial actuator. Further, while the embodiments below describe various forms of actuation mechanisms for switching the flow of fluid, other embodiments are contemplated that are consistent with the principles described herein.

Further, the embodiments described below may use ceramic materials for the piston and/or the bored structure. The pistons and bored structures may be manufactured with tight tolerances in order to produce clearances less than <NUM> microns. Tight tolerances may provide for fluid tight seals between the conduits of the actuation mechanism, without using additional deformable sealing elements between the components. Depending on the exact requirements of a particular design, the tolerances and material properties of the embodiments described herein may change. For example, operating pressure, piston and/or bore size, choice of material, and the like, could all impact the ability to achieve sealing via precision machined parts without the use of an external seal component (e.g. a deformable seal).

Ceramic materials may be particularly advantageous in the embodiments described herein due to their ability to manufacture with extremely tight tolerances. Further, the high hardness of ceramics, along with the resistance to wear and corrosion and oxidation of ceramics, may make ceramic materials particularly advantageous. Ceramics may also prevent the introduction of undesirable temperature effects. However, other chemically inert metals or other materials are contemplated. Examples of other materials may include stainless steel such as Nitronic <NUM>, Titanium, Nickel-Cobalt base alloys such as MP35N®, Tantalum or the like.

The bored structures in the embodiments below are shown having various inlet and outlet conduits that allow fluid to flow through the piston-occupied zone of the actuation mechanism. While the inlet and outlet conduits are shown as openings in the bored structures in each cross sectional view shown below in <FIG>, <FIG>, <FIG> and <FIG>, it should be understood that a manifold or housing may be attached to the exterior of the bored structures of each embodiment for connecting external fluid conduits thereto. Such a manifold or housing may be, for example, made from a different material such as plastic. The bored structure could be housed in the plastic manifold in a variety of ways, including but not limited to being pressed in, thermally shrinking the plastic manifold around the bore, or the like. Housing the bored structure in this way may provide for ease of connecting and aligning the ceramic (or other material) inlets and outlets with the inlet and outlet channels of solvent lines in a liquid chromatography system.

Further, while the embodiments described hereinbelow in <FIG>, <FIG>, <FIG> and <FIG> are shown where the pistons and respective bored structures are cylindrical in shape and structure, it is also conceivable that the pistons and bored structures described herein may take the form of various shapes not limited to cylinders. Further, while the pistons are described as being the moving components in the embodiments described hereinbelow, it should also be understood that the bored structures could be the component that moves, rather than the piston. It should be understood that the embodiments contemplated herein require relative movement between the pistons and their respective bored structures, but that movement of either or both of these components could create the requisite relative movement.

While not shown in the cross sectional views below, the actuation mechanisms described herein may utilize one or more hard stop features to facilitate alignment between the pistons with their respective bored structures and help to control and prevent unwanted movement. In embodiments that utilize hard stop features, impact absorbing material could be added to any of these hard stop features to reduce wear.

Referring now to <FIG>, a schematic cross-sectional view of an actuation mechanism <NUM> for a switching valve is depicted in accordance with one embodiment. The actuation mechanism <NUM> includes a piston <NUM> located within a bored structure <NUM>. An inlet conduit <NUM> and an outlet conduit <NUM> provide fluid through the actuation mechanism <NUM>. The piston <NUM> includes a keyed flat surface <NUM> cut out therefrom, which creates an open space <NUM> between the piston <NUM> and the bored structure <NUM>. While there is a space shown between the piston <NUM> and the bored structure <NUM>, it should be understood that the invention contemplates utilizing extremely tight clearances between the piston <NUM> and the bored structure <NUM> so that almost no space exists therebetween. Again, clearances of less than <NUM> microns are contemplated in order to retain a fluid tight seal when the piston <NUM> is rotated to close off one or more of the inlet and the outlet conduits <NUM>, <NUM> without using any external sealing components or deformable seals.

While only a top cross sectional view of the actuation mechanism <NUM> is shown, it should be understood that the actuation mechanism includes an appropriate depth to accommodate the inlet and outlet conduits <NUM>, <NUM> and to accommodate the attachment of the piston <NUM> to a motor for effectuating rotational movement. While the depth of the piston <NUM> and bored structure <NUM> may be greater than the amount needed to accommodate the inlet and outlet conduits <NUM>, <NUM>, the keyed flat surface <NUM> and the open space <NUM> may be particularly fashioned with a depth that corresponds to the depth needed to accommodate the inlet and outlet conduits <NUM>, <NUM> in order to minimize the volume of the open space <NUM>.

The actuation mechanism <NUM> may be configured to open and close the inlet and outlet conduits <NUM>, <NUM> via rotation of the piston <NUM> about the bored structure <NUM>. The position in <FIG> shows the actuation mechanism <NUM> in an open state whereby fluid can flow through the inlet <NUM> into the open space <NUM> created by the keyed flat surface <NUM> of the piston <NUM>. Clockwise rotation from this open position would close the inlet conduit <NUM>, while counter-clockwise rotation would close the outlet. The actuation mechanism <NUM> may deploy either of these rotations in order to effectuate opening and closing of the conduits <NUM>, <NUM>. Moreover, the angle θ is shown, which defines the rotational distance between the inlet conduit <NUM> and the outlet conduit <NUM>. It may be desirable to include a relatively small angle θ that is less, for example, than <NUM> degrees, in order to reduce the size of the open space <NUM> in the system. Reducing the size of this open space <NUM> and quickly opening and closing the inlets via a small angle θ may help to reduce or eliminate pressure pulses created by the actuation mechanism <NUM>.

<FIG> depicts a schematic cross-sectional view of another actuation mechanism <NUM> for a switching valve, in accordance with one embodiment. The actuation mechanism <NUM> includes a piston <NUM> located within a bored structure <NUM>. An inlet conduit <NUM> and an outlet conduit <NUM> provide fluid through the actuation mechanism <NUM>. The piston <NUM> includes a conduit <NUM> that extends therethrough to connect the inlet conduit <NUM> with the outlet conduit <NUM> when the piston <NUM> is in the relative position to the bored structure <NUM> that is shown. Like the previous embodiments, clearances of less than <NUM> microns are contemplated between the piston <NUM> and the bored structure <NUM> in order to retain a fluid tight seal when the piston <NUM> is rotated to close off the inlet and outlet conduits <NUM>, <NUM> without using any external sealing components or deformable seals.

While only a top cross sectional view of the actuation mechanism <NUM> is shown, it should be understood that the actuation mechanism includes an appropriate depth to accommodate the inlet and outlet conduits <NUM>, <NUM> and to accommodate the attachment of the piston <NUM> to a motor for effectuating rotational movement. The actuation mechanism <NUM> may be configured to open and close the inlet and outlet conduits <NUM>, <NUM> via rotation of the piston <NUM> about the bored structure <NUM> in either direction relative to the position shown. The position in <FIG> shows the actuation mechanism <NUM> in an open state whereby fluid can flow from the inlet conduit <NUM> through the conduit <NUM> of the piston <NUM> and out of the actuation mechanism <NUM> through the outlet conduit <NUM>. The actuation mechanism <NUM> may deploy either clockwise or counterclockwise rotation in order to effectuate opening and closing. Moreover, the angle θ between the inlet conduit <NUM> and the outlet conduit <NUM> is shown to be <NUM> degrees, creating a straight line through the actuation mechanism <NUM> when the actuation mechanism <NUM> is open. Such an embodiment may reduce the amount of rotation necessary to open and close the valve. However, including this straight-line approach is only feasible when there is a single inlet and a single outlet for each actuation mechanism <NUM>.

<FIG> depicts a schematic cross-sectional view of another actuation mechanism <NUM> for a switching valve, in accordance with one embodiment. The actuation mechanism <NUM> includes a piston <NUM> located within a bored structure <NUM>. An inlet conduit <NUM> and an outlet conduit <NUM> provide fluid through the actuation mechanism <NUM>. The piston <NUM> includes a conduit <NUM> that extends therethrough to connect the inlet conduit <NUM> with the outlet conduit <NUM> when the piston <NUM> is in the relative position to the bored structure <NUM> that is shown. The conduit <NUM> of the piston <NUM> may be fashioned by drilling two perpendicular holes into the piston <NUM> that are <NUM> degrees apart and which meet in the middle of the piston <NUM>. Like the previous embodiments, clearances of less than <NUM> microns are contemplated between the piston <NUM> and the bored structure <NUM> in order to retain a fluid tight seal when the piston <NUM> is rotated to close off the inlet and outlet conduits <NUM>, <NUM> without using any external sealing components or deformable seals.

While only a top cross sectional view of the actuation mechanism <NUM> is shown, it should be understood that the actuation mechanism includes an appropriate depth to accommodate the inlet and outlet conduits <NUM>, <NUM> and to accommodate the attachment of the piston <NUM> to a motor for effectuating rotational movement. The actuation mechanism <NUM> may be configured to open and close the inlet and outlet conduits <NUM>, <NUM> via rotation of the piston <NUM> about the bored structure <NUM> in either direction relative to the position shown. The position in <FIG> shows the actuation mechanism <NUM> in an open state whereby fluid can flow from the inlet conduit <NUM> through the conduit <NUM> of the piston <NUM> and out of the actuation mechanism <NUM> through the outlet conduit <NUM>. The actuation mechanism <NUM> may deploy either clockwise or counterclockwise rotation in order to effectuate opening and closing. Moreover, the angle θ between the inlet conduit <NUM> and the outlet conduit <NUM> is shown to be <NUM> degrees, creating a perpendicular angle within the piston <NUM> through which the fluid must flow to exit from the outlet conduit <NUM> when the actuation mechanism <NUM> is open. This change in flow direction may be desirable in reducing pressure pulses from opening and closing downstream from the actuation mechanism <NUM>. This embodiment may function similar to the embodiment of <FIG>, whereby the amount of rotation necessary to open and close the valve is reduced relative to the embodiment of <FIG>. However, including this approach is only feasible when there is a single inlet and a single outlet for each actuation mechanism <NUM>.

<FIG> depicts a schematic cross-sectional view of another actuation mechanism <NUM> for a switching valve, in accordance with one embodiment. The actuation mechanism <NUM> includes a piston <NUM> located within a bored structure <NUM>. An inlet conduit <NUM> and an outlet conduit <NUM> provide fluid through the actuation mechanism <NUM>. The piston <NUM> includes a conduit <NUM> that extends therethrough to connect the inlet conduit <NUM> with the outlet conduit <NUM> when the piston <NUM> is in the relative position to the bored structure <NUM> that is shown. Like the previous embodiments, clearances of less than <NUM> microns are contemplated between the piston <NUM> and the bored structure <NUM> in order to retain a fluid tight seal when the piston <NUM> is moved to close off the inlet and outlet conduits <NUM>, <NUM> without using any external sealing components or deformable seals. Unlike the previous embodiments, movement to open and close the actuation mechanism <NUM> of the piston <NUM> relative to the bored structure <NUM> is axial rather than rotational.

While only a side cross sectional view of the actuation mechanism <NUM> is shown, it should be understood that the actuation mechanism includes an appropriate depth to accommodate the inlet and outlet conduits <NUM>, <NUM> and to accommodate the attachment of the piston <NUM> to a motor for effectuating axial movement. The actuation mechanism <NUM> may be configured to open and close the inlet and outlet conduits <NUM>, <NUM> via axial movement of the piston <NUM> relative to the bored structure <NUM> in either direction relative to the position shown. The position in <FIG> shows the actuation mechanism <NUM> in an open state whereby fluid can flow from the inlet conduit <NUM> through the conduit <NUM> of the piston <NUM> and out of the actuation mechanism <NUM> through the outlet conduit <NUM>. While the previous embodiments may deploy rotational movement via a stepper motor, servo motor, or other rotational actuator, the embodiment shown in <FIG> may be controlled via a solenoid, voice coil, piezoelectric motor or other axial movement system.

<FIG> depicts a schematic view of another gradient proportioning valve 2C, in accordance with one embodiment. The gradient proportioning valve 2C is shown schematically including four separate inlet ports <NUM> which provide fluid via a conduit or channel to two separate switching valve 17A, 17B. As shown, each switching valve 17A, 17B is configured to receive fluid from two separate inlet ports <NUM> and provide a single outlet from the respective switching valves 17A, 17B. The single outlets of the two separate switching valves 17A, 17B each separately outlet fluid to a downstream mix point <NUM>. At the mix point <NUM>, the fluid is combined into a single stream from the two separate streams received from the switching valves 17A, 17B. Downstream from the mix point <NUM> is an outlet <NUM>.

<FIG> shows one example schematic view of the gradient proportioning valve 2C where two inlet channels are connected to one valve 17A, 17B. Further, the schematic shows no accumulator chambers <NUM>. In other embodiments contemplated, accumulator chambers may exist for each inlet port <NUM> prior to providing the fluid to the switching valves 17A, 17B. The schematic having two inlet channels for each valve can be used to describe embodiments consistent with the actuation mechanisms shown in <FIG> and described hereinbelow.

<FIG> depicts a schematic cross-sectional view of another actuation mechanism <NUM> for a switching valve, in accordance with one embodiment. The actuation mechanism <NUM> includes a piston <NUM> located within a bored structure <NUM>. A first inlet conduit <NUM> and a second inlet conduit <NUM> provide fluid to the actuation mechanism <NUM> from different fluid sources. The piston <NUM> includes a conduit <NUM> that extends from exterior of the piston <NUM> into the middle of the piston <NUM>. An outlet conduit <NUM> is drilled axially through the piston <NUM> to allow fluid to flow out of the actuation mechanism <NUM>. Like the previous embodiments, clearances of less than <NUM> microns are contemplated between the piston <NUM> and the bored structure <NUM> in order to retain a fluid tight seal when the piston <NUM> is rotated to close off the inlet and outlet conduits <NUM>, <NUM> without using any external sealing components or deformable seals.

While only a top cross sectional view of the actuation mechanism <NUM> is shown, it should be understood that the actuation mechanism includes an appropriate depth to accommodate the inlet and outlet conduits <NUM>, <NUM>, to accommodate the attachment of the piston <NUM> to a motor for effectuating rotational movement, and to accommodate connecting the outlet <NUM> of the piston <NUM> to the rest of a downstream liquid chromatography system.

The actuation mechanism <NUM> may be configured to open and close the respective first and second inlet conduits <NUM>, <NUM> via rotation of the piston <NUM> about the bored structure <NUM>. The position in <FIG> shows the actuation mechanism <NUM> in a state where the first inlet conduit <NUM> is in an open state whereby fluid can flow from the inlet conduit <NUM> through the conduit <NUM> of the piston <NUM> and out of the axially drilled outlet conduit <NUM> of the piston <NUM>. The actuation mechanism <NUM> may deploy either clockwise or counterclockwise rotation on the piston <NUM> relative to the bored structure <NUM> in order to effectuate opening and closing. For example, clockwise rotation may move the piston <NUM> from opening the first inlet <NUM> to opening the second inlet <NUM>. Alternatively, from the position shown, a counterclockwise rotation may close both the first and second inlets <NUM>, <NUM>. In the embodiment shown, the closed state may also occur when the piston <NUM> is rotated so that the outlet of the conduit <NUM> is facing the wall of the bored structure <NUM> that is located between the first and second inlets <NUM>, <NUM>. The present embodiment contemplates the actuation mechanism <NUM> being able to toggle between two separate inlets <NUM>, <NUM>, with one inlet open at a given time, and whereby the actuation mechanism always includes the same outlet <NUM>.

Moreover, the angle θ between each of the first and second inlet conduits <NUM>, <NUM> defines the rotational distance between the first inlet conduit <NUM> and the second inlet conduit <NUM>. It may be desirable to include a relatively small angle θ that is less, for example, than <NUM> degrees, in order to allow for the actuation mechanism <NUM> to toggle between positions more quickly. This may help to reduce or eliminate pressure pulses created by the actuation mechanism <NUM>.

<FIG> depicts a schematic cross-sectional view of another actuation mechanism <NUM> for a switching valve, in accordance with one embodiment. The actuation mechanism <NUM> includes a piston <NUM> located within a bored structure <NUM>. A first inlet conduit <NUM> and a second inlet conduit <NUM> in the bored structure <NUM> provide fluid to the actuation mechanism <NUM> from different fluid sources. The bored structure <NUM> further includes an outlet conduit <NUM> located between the first and second inlet conduits <NUM>, <NUM>. The piston <NUM> includes a keyed flat surface <NUM> cut out therefrom, which creates an open space <NUM> between the piston <NUM> and the bored structure <NUM>. While there is a space shown between the piston <NUM> and the bored structure <NUM>, it should be understood that the invention contemplates utilizing extremely tight clearances between the piston <NUM> and the bored structure <NUM> so that almost no space exists therebetween. Again, clearances of less than <NUM> microns are contemplated in order to retain a fluid tight seal when the piston <NUM> is rotated to close off one or more of the inlet and the outlet conduits <NUM>, <NUM>, <NUM> without using any external sealing components or deformable seals.

The actuation mechanism <NUM> may be configured to open and close the respective first and second inlet conduits <NUM>, <NUM> via rotation of the piston <NUM> about the bored structure <NUM>. The position in <FIG> shows the actuation mechanism <NUM> in a state where the first inlet conduit <NUM> is in an open state whereby fluid can flow through the inlet <NUM> into the open space <NUM> created by the keyed flat surface <NUM> of the piston <NUM>. Clockwise or counterclockwise rotation from this open position would close the first inlet conduit <NUM>. Similarly, rotating the piston <NUM> clockwise further so that the keyed flat surface <NUM> extends between the second inlet conduit <NUM> and the outlet conduit <NUM> would open the second inlet conduit <NUM> and close the first inlet conduit <NUM>.

The actuation mechanism <NUM> may deploy either of these rotations in order to effectuate opening and closing of the first and second inlet conduits <NUM>, <NUM>. Moreover, the angles θ are shown, between each of the first inlet conduit <NUM> and the outlet conduit <NUM>, and between the second inlet conduit <NUM> and the outlet conduit <NUM>. These angles θ define the rotational distance between the respective conduits <NUM>, <NUM>, <NUM>. It may be desirable to include a relatively small angle θ that is less, for example, than <NUM> degrees, in order to reduce the size of the open space <NUM> in the system. Reducing the size of this open space <NUM> and quickly opening and closing the inlets via a small angle θ may help to reduce or eliminate pressure pulses created by the actuation mechanism <NUM>.

<FIG> depicts a schematic cross-sectional view of another actuation mechanism <NUM> for a switching valve, in accordance with one embodiment. The actuation mechanism <NUM> includes a piston <NUM> located within a bored structure <NUM>. A first inlet conduit <NUM> and a second inlet conduit <NUM> provide fluid from the bored structure <NUM> to the piston <NUM>. A combined outlet conduit <NUM> allows fluid to leave the actuation mechanism <NUM>. The piston <NUM> includes a conduit <NUM> that extends therethrough to connect the second inlet conduits <NUM> with the outlet conduit <NUM> when the piston <NUM> is in the relative position to the bored structure <NUM> that is shown. The piston <NUM> can move axially leftward to connect the first inlet conduit <NUM> to the outlet conduit <NUM>. Alternatively, the piston can move axially rightward to close off each of the first and second inlet conduits <NUM>, <NUM>.

Like the previous embodiments, clearances of less than <NUM> microns are contemplated between the piston <NUM> and the bored structure <NUM> in order to retain a fluid tight seal when the piston <NUM> is moved to open or close off the inlet and outlet conduits <NUM>, <NUM> without using any external sealing components or deformable seals. Again, unlike the embodiment shown in <FIG>, movement of the piston <NUM> relative to the bored structure <NUM> is axial rather than rotational to open and close the two inlet conduits <NUM>, <NUM> with the actuation mechanism <NUM>.

<FIG> depicts a schematic view of another gradient proportioning valve 2D, in accordance with one embodiment. The gradient proportioning valve 2D is shown schematically including four separate inlet ports <NUM> which provide fluid via a conduit or channel to a single switching valve 17A. As shown, the switching valve 17A is configured to receive fluid from each of the four separate inlet ports <NUM> and provide a single outlet from the switching valves 17A. Downstream from the single switching valve may be a downstream mix point <NUM> which may be a greater volume region that helps mix fluid after the switching valve 17A but prior to the outlet. Rather than being a separate volumetric chamber, the mix point <NUM> may be incorporated in the actuation mechanism of the switching valve 17A. Downstream from the mix point <NUM> is an outlet <NUM>.

<FIG> shows one example schematic view of the gradient proportioning valve 2D where all four inlet channels are connected to the single switching valve 17A. Further, the schematic shows no accumulator chambers <NUM>. In other embodiments contemplated, accumulator chambers may exist for each inlet port <NUM> prior to providing the fluid to the switching valve 17A. The schematic having four inlet channels for each valve can be used to describe embodiments consistent with the actuation mechanisms shown in <FIG> described hereinbelow.

<FIG> depicts a schematic cross-sectional view of another actuation mechanism <NUM> for a switching valve, in accordance with one embodiment. The actuation mechanism <NUM> includes a piston <NUM> located within a bored structure <NUM>. A first inlet conduit <NUM>, a second inlet conduit <NUM>, a third inlet conduit <NUM>, and a fourth inlet conduit <NUM> each provide fluid to the actuation mechanism <NUM> from different fluid sources. The piston <NUM> includes a conduit <NUM> that extends from exterior of the piston <NUM> into the middle of the piston <NUM>. An outlet conduit <NUM> is drilled axially through the piston <NUM> to allow fluid to flow out of the actuation mechanism <NUM>. Like the previous embodiments, clearances of less than <NUM> microns are contemplated between the piston <NUM> and the bored structure <NUM> in order to retain a fluid tight seal when the piston <NUM> is rotated to close off the inlet and outlet conduits <NUM>, <NUM>, <NUM>, <NUM> without using any external sealing components or deformable seals.

While only a top cross sectional view of the actuation mechanism <NUM> is shown, it should be understood that the actuation mechanism includes an appropriate depth to accommodate the inlet and outlet conduits <NUM>, <NUM>, <NUM>, <NUM> to accommodate the attachment of the piston <NUM> to a motor for effectuating rotational movement, and to accommodate connecting the outlet <NUM> of the piston <NUM> to the rest of a downstream liquid chromatography system.

The actuation mechanism <NUM> may be configured to open and close the respective first, second, third and fourth inlet conduits <NUM>, <NUM>, <NUM>, <NUM> via rotation of the piston <NUM> about the bored structure <NUM>. The position in <FIG> shows the actuation mechanism <NUM> in a state where the second inlet conduit <NUM> is in an open state whereby fluid can flow from the second inlet conduit <NUM> through the conduit <NUM> of the piston <NUM> and out of the axially drilled outlet conduit <NUM> of the piston <NUM>. The actuation mechanism <NUM> may deploy either clockwise or counterclockwise rotation on the piston <NUM> relative to the bored structure <NUM> in order to effectuate opening and closing of the various inlet conduits <NUM>, <NUM>, <NUM>, <NUM>. For example, clockwise rotation may move the piston <NUM> from opening the second inlet conduit <NUM> to opening the third inlet conduit <NUM>. Alternatively, from the position shown, a counterclockwise rotation may open the first inlet conduit <NUM>. In the embodiment shown, the closed state may also occur when the piston <NUM> is rotated so that the outlet of the conduit <NUM> is facing the wall of the bored structure <NUM> that is located either between one of the inlet conduits <NUM>, <NUM>, <NUM>, <NUM> or counterclockwise to the first inlet conduit <NUM> or clockwise to the fourth inlet conduit <NUM>. The present embodiment contemplates the actuation mechanism <NUM> being able to toggle between the four inlet conduits <NUM>, <NUM>, <NUM>, <NUM>, with one inlet open at a given time, and whereby the actuation mechanism always includes the same outlet <NUM>.

Moreover, the angle θ between each of the inlet conduits <NUM>, <NUM>, <NUM>, <NUM> defines the rotational distance between the various inlet conduits <NUM>, <NUM>, <NUM>, <NUM>. It may be desirable to include a relatively small angle θ that is less, for example, than <NUM> degrees, in order to allow for the actuation mechanism <NUM> to toggle between positions more quickly. This may help to reduce or eliminate pressure pulses created by the actuation mechanism <NUM>.

While the embodiments above have been described using either axial or rotational movement, other embodiments contemplated for actuation mechanisms could use the combination of both axial and rotational movement. For example, it may be contemplated that the inlets could actually be positioned axially spaced apart as well as rotationally spaced apart. For example, in the embodiment shown in <FIG>, rather than having all four inlets come to the piston <NUM> at the same depth, two inlets (for example, inlets <NUM>, <NUM>) may be spaced apart axially relative to the other two inlets (for example, inlets <NUM>, <NUM>). Using both axial and rotational spacing may allow for the total space between the various inlets to be reduced. For example, if the inlets <NUM>, <NUM>, <NUM>, <NUM> are located at corners of a diamond or square shape, movement of the piston from any one inlet to another would be close to the same. In contrast, the embodiment where the inlets <NUM>, <NUM>, <NUM>, <NUM> come to the piston <NUM> at a single plane each separated by the angle θ, the movement between the inlet <NUM> and the inlet <NUM> is much greater than the movement between the inlet <NUM> and the inlet <NUM>. Various embodiments of the above described actuation mechanisms having more than one inlet may employ both rotational and axial movement in combination to reduce the space between the various inlets.

Still further, while the embodiments described hereinabove show four inlet ports for each gradient proportioning valve 2D, the actuation mechanism described herein may be incorporated into gradient proportioning valves having any number of inlets for any number of solvent lines. Further, while the embodiments of actuation mechanisms show single inlets, two inlets, or four inlets, the principles of the actuation mechanisms described hereinabove may be applied to other number of inlets, such as three inlets, or more than <NUM> inlets. Whatever the embodiment, the actuation mechanisms contemplated herein may include a single outlet, no matter how many inlets the actuation mechanisms are configured for.

Methods of operating switching valves for a gradient proportioning valve of a liquid chromatography system are further contemplated. For example, methods contemplated herein include providing a gradient proportioning valve, such as one of the valves 17A, 17B, 17C, 17D described herein, including a manifold having a plurality of conduits. Methods include receiving a plurality of fluids in a plurality of inlet ports of the gradient proportioning valve, opening and closing each of a plurality of conduits in a controlled manner with an actuation mechanism, such as one of the actuation mechanism <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, having a piston, such as one of the pistons <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> located within a bored structure, such as one of the bored structures <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, surrounding the piston. Methods include maintaining a fluid tight seal between the piston and the bored structure during the opening and closing, wherein the piston and the bored structure have a tight tolerance configured to create the fluid tight seal. Methods include mixing the plurality of fluids in a controlled manner within the manifold of the gradient proportioning valve, and outputting the fluid composition from a common outlet port of the gradient proportioning valve.

Still further methods include preventing unwanted fluidic pressure pulses in the manifold with the actuation mechanism through the minimization of internal fluid volumes within the piston and the bored structure. Moreover, methods contemplated include opening, with the actuation mechanism, two or more of the plurality of conduits such as with the embodiments shown in <FIG>.

Methods further include rotating the piston about the bored structure to open and close the at least one of the plurality of conduits in the controlled manner, such as in the embodiments shown in <FIG>, <FIG>, <FIG> and <FIG>. Alternatively, methods include moving the piston axially within the bored structure to open and close the at least one of the plurality of conduits in the controlled manner, such as in the embodiments shown in <FIG> and <FIG>. Additionally, methods may include moving the piston both axially and with rotation relative to the bored structure as described hereinabove.

Claim 1:
A gradient proportioning valve (<NUM>) for liquid chromatography comprising:
a plurality of inlet ports (<NUM>) configured to receive a plurality of fluids;
a manifold (<NUM>) connected to each of the plurality of inlet ports (<NUM>) configured to mix the plurality of fluids in a controlled manner to provide a fluid composition, the manifold (<NUM>) including a plurality of conduits (<NUM>) internal to the manifold (<NUM>), the plurality of inlet ports (<NUM>) each configured to provide fluid to a respective one of the plurality of conduits (<NUM>) of the manifold (<NUM>);
an actuation mechanism (<NUM>) having a piston (<NUM>) located within a bored structure (<NUM>) surrounding the piston (<NUM>), the actuation mechanism (<NUM>) configured to open and close at least one of the plurality of conduits (<NUM>) in a controlled manner wherein the piston (<NUM>) and the bored structure (<NUM>) have a tight tolerance configured to create a fluid tight seal when the actuation mechanism (<NUM>) closes the at least one of the plurality of conduits (<NUM>);
a common outlet port configured to receive the fluid composition; and
at least one accumulator chamber (<NUM>) located downstream from at least one of the plurality of inlet ports (<NUM>), the respective one conduit (<NUM>) of the manifold (<NUM>), and upstream from the actuation mechanism (<NUM>) and the common outlet port, the at least one accumulator chamber (<NUM>) having a compliant diaphragm (<NUM>) disposed in a back of the at least one accumulator chamber (<NUM>) opposite the conduit (<NUM>) of the manifold (<NUM>).