Gas Separation Devices

Abstract

A gas separation device for use in conjunction with a liquid chromatography system is provided. The gas separation device includes a housing defining a fluid flow path between an exterior surface and an interior surface. The fluid flow path includes an inlet section, a diffuser section, a recombination section, and an outlet section. Air bubbles contained within the fluid are trapped within the diffuser section when fluid flow is in a forward direction. Fluid flow through the gas separation device is reversible to remove trapped air bubbles from within the gas separation device. In this operating condition, fluid is delivered from the gas separation device to a waste stream, ensuring that air bubbles are excluded from the liquid chromatography system. The gas separation device is configured to separate 0.001 mL of air bubbles during forward fluid flow. -1 ~0.51mL -1 The air capture efficiency (ATER) can be shown.

Description

[Technical field]

[0001] Field The present disclosure relates generally to gas separation devices and methods, and more particularly to gas separation devices and methods for use with liquid chromatography systems. [Background technology]

[0002] background Liquid chromatography methods are commonly used to separate and / or purify molecules of interest, such as proteins, nucleic acids, and polysaccharides, from a fluid mixture. For example, affinity chromatography specifically involves passing a fluid mixture over a matrix to which a ligand (i.e., a specific binding partner) specific for the molecule of interest is attached. Upon contact with the ligand, the molecule of interest is bound to the matrix and is therefore removed from the fluid mixture.

[0003] During delivery of fluids containing molecules of interest and other fluids for use in a chromatography device, air bubbles can be introduced into the system, which is generally detrimental to the functioning of the liquid chromatography device, and it is desirable to reduce these instances. Summary of the Invention

[0004] Abstract In a first example ("Example 1"), a gas separation device includes a housing defining a fluid flow path between an exterior surface and an interior surface, the housing having an inlet in communication with the fluid flow path and an outlet in communication with the fluid flow path, the housing operable to permit fluid flow in a forward direction from the inlet to the outlet and a reverse direction from the outlet to the inlet. The fluid flow path defines a fluid flow path volume and includes an inlet portion disposed to receive fluid from the inlet during forward fluid flow through the housing, where the inlet portion defines an inlet partial volume, a diffuser portion disposed to receive fluid from the inlet portion during forward fluid flow through the housing, where the diffuser portion defines a diffuser partial volume, a recombination portion disposed to receive fluid from the diffuser portion during forward fluid flow through the housing, where the recombination portion defines a recombination partial volume, and an outlet portion disposed to receive fluid from the recombination portion during forward fluid flow through the gas separation device, where the outlet portion defines an outlet partial volume. The gas separation device is configured to separate 0.001 mL of gas during forward fluid flow through the housing. -1 ~0.51mL -1 The air trapping effectiveness ratio (ATER) is configured to be:

[0005] In a second example ("Example 2"), the device of Example 1 includes a gas separation device configured to exhibit a transition volume during forward fluid flow through the housing that is less than or equal to 5 times the value of the fluid flow path volume.

[0006] In a third example ("Example 3"), the device of Example 1 includes that the gas separation device further includes one fluid flow path exiting the outlet.

[0007] In a fourth example ("Example 4"), the device of Example 1 further includes a manifold in fluid communication with the outlet, the manifold including a point that divides fluid exiting the outlet into a plurality of fluid flow paths.

[0008] In a fifth example ("Example 5"), the device of Example 4 includes wherein the plurality of fluid flow paths includes at least two fluid flow paths.

[0009] In a sixth example ("Example 6"), the device of Example 1 includes, wherein the inlet partial volume and the diffuser partial volume together are between 10% and 75% of the fluid flow path volume.

[0010] In a seventh example ("Example 7"), the device of Example 1 includes a first average fluid velocity used to determine ATER defined by the velocity of fluid flowing through the inlet, and a second average fluid velocity used to determine ATER defined by the velocity of fluid flowing through the diffuser portion.

[0011] In an eighth example ("Example 8"), the device of Example 7 further includes a point where ATER is defined by the ratio of the second average fluid velocity to the first average fluid velocity divided by the diffuser partial volume.

[0012] In a ninth example ("Example 9"), the device of Example 1 further includes a point where at least one of the inner and outer surfaces of the diffuser portion defines a generally dome-shaped longitudinal profile.

[0013] In a tenth example ("Example 10"), the device of Example 1 further includes a point where at least one of the inner and outer surfaces of the diffuser portion defines a generally flat longitudinal profile.

[0014] In an eleventh example ("Example 11"), the device of Example 1 further includes a point where at least one of the inner and outer surfaces of the diffuser portion defines a conical or frustoconical profile.

[0015] In a twelfth example ("Example 12"), the device of Example 1 further includes that at least a portion of the housing is translucent or transparent such that the gas volume within the diffuser portion is visible through the housing.

[0016] In a thirteenth example ("Example 13"), the device of Example 1 further includes, wherein the recombination portion is defined by a plurality of individual channels extending between an inner surface and an outer surface of the fluid flow path.

[0017] In a fourteenth example ("Example 14"), the device of Example 1 further includes a point where the recombination portion is defined by an annular channel extending between an inner surface and an outer surface of the fluid flow path.

[0018] In a fifteenth example ("Example 15"), the device of Example 1 further includes a point where the recombination portion is defined by inner and outer surfaces of a fluid flow path having a concentric circular configuration.

[0019] In a sixteenth example ("Example 16"), a fluid system includes a gas separation device having a housing defining a fluid flow path between an exterior surface and an interior surface, the housing having an inlet in communication with the fluid flow path and an outlet in communication with the fluid flow path, the housing operable to enable forward and reverse fluid flow from the inlet to the outlet, the fluid flow path defining a fluid flow path volume. The system further includes a fluid source coupled to the inlet of the gas separation device and at least one chromatography device including an inlet coupled to the outlet of the gas separation device, the fluid source configured to deliver a forward flow through the gas separation device and the chromatography device, the chromatography device operable to enable a reverse flow through the chromatography device, and the gas separation device configured to deliver less than 0.001 mL of fluid during forward flow through the housing. -1 ~0.51mL -1 The air capture efficiency (ATER) is calculated based on the air capture efficiency (ATER) of 1.

[0020] In a seventeenth example ("Example 17"), the system of Example 16 includes a first average fluid velocity used to determine ATER defined by the velocity of fluid flowing through the inlet, a second average fluid velocity used to determine ATER defined by the velocity of fluid flowing through the diffuser portion, and ATER defined by the ratio of the second average fluid velocity to the first average fluid velocity divided by the volume of the diffuser portion.

[0021] In an eighteenth example ("Example 18"), the system of Example 16 further includes, wherein the chromatography device has a total volume defined by the volume between a fluid inlet of the chromatography device and a fluid outlet of the chromatography device, and a fluid flow volume of the gas separation device is less than or equal to 50% of the total volume of the chromatography device.

[0022] In a nineteenth example ("Example 19"), the system of Example 16 includes that the gas separation device is configured to exhibit a transition volume less than or equal to five times the value of the fluid flow path volume of the gas separation device during forward flow through the housing.

[0023] In a twentieth example ("Example 20"), the system of Example 16, wherein the gas separation device further includes a manifold in fluid communication with at least one outlet, the manifold including a point for dividing fluid exiting the outlet into a plurality of fluid flow paths.

[0024] In a twenty-first example ("Example 21"), the system of Example 16 includes where the fluid flow path includes an inlet portion arranged to receive fluid from the inlet during forward flow through the housing, a diffuser portion arranged to receive fluid from the inlet portion during forward flow through the housing, where the diffuser portion defines a diffuser portion volume, a recombination portion arranged to receive fluid from the diffuser portion during forward flow through the housing, and an outlet portion arranged to receive fluid from the recombination portion during forward flow through the gas separation device.

[0025] In a twenty-second example ("Example 22"), the system of Example 21 includes that at least a portion of one or both of the inner and outer surfaces of the fluid flow path defining the diffuser portion is translucent or transparent, such that air bubbles can be observed within the diffuser portion.

[0026] In a twenty-third example ("Example 23"), a method of trapping and releasing a volume of gas bubbles in a gas separation device, the gas separation device having a housing defining a fluid flow path having an exterior surface and an interior surface, the housing having an inlet in fluid communication with the fluid flow path and an outlet in fluid communication with the fluid flow path, the method including delivering a fluid in a forward direction through the flow path such that the fluid flows through the gas separation device from the inlet to the outlet. The method further includes further trapping the volume of gas in the gas separation device, where at least a portion of at least one of the interior and exterior surfaces of the housing is translucent to allow observation of the volume of gas, and ceasing delivery of fluid through the fluid flow path. The method further includes delivering a fluid in a reverse direction through the fluid flow path such that the fluid flows from the outlet to the inlet to remove at least a portion of the volume of gas bubbles from the gas separation device.

[0027] In a twenty-fourth example ("Example 24"), the method of Example 23 further includes, wherein the fluid flow path includes an inlet portion arranged to receive fluid from the inlet during forward fluid flow through the housing, a diffuser portion arranged to receive fluid from the inlet portion during forward flow through the housing, where the diffuser portion defines a diffuser portion volume, a recombination portion arranged to receive fluid from the diffuser portion during forward flow through the housing, and an outlet portion arranged to receive fluid from the recombination portion during forward flow through the gas separation device.

[0028] In a twenty-fifth example ("Example 25"), the method of Example 24 further includes trapping the volume of gas bubbles includes trapping the volume of gas bubbles within a diffuser portion of the gas separation device.

[0029] In a twenty-sixth example ("Example 26"), the method of Example 23 further includes reversing the flow when the bubble volume approaches a maximum bubble volume defined by about 95% of the diffuser partial volume.

[0030] In a twenty-seventh example ("Example 27"), the method of Example 23 further includes delivering fluid through the fluid flow path in a forward direction from the inlet to the outlet of the housing after a portion of the volume of bubbles has exited the gas separation device.

[0031] In a twenty-eighth example ("Example 28"), the method of Example 23 further comprises: -1 ~0.51mL -1 The figures further include points showing the air capture effectiveness ratio (ATER).

[0032] In a twenty-ninth example ("Example 29"), the method of Example 23 further includes, during forward flow through the housing, the gas separation device exhibits a transition volume that is less than or equal to 5 times the value of the fluid flow path volume.

[0033] In a thirty-first example ("Example 30"), the method of Example 24 further includes, wherein the volume of bubbles is between 1% and 100% of the fluid flow channel volume.

[0034] In a thirty-first example ("Example 31"), the method of Example 23 further includes that the outlet of the gas separation device is fluidly connected to an inlet of a chromatography device, thereby disposing the gas separation device and the chromatography device in series, and the method further includes delivering a fluid through the outlet of the gas separation device to the inlet of the chromatography device.

[0035] In a thirty-second example ("Example 32"), a gas separation device includes an outer housing, an inlet coupled to the outer housing, an inner component disposed within the outer housing and defining a diffuser surface and a core, where the diffuser surface has a generally dome-shaped longitudinal profile, a collector disposed below the inner component, and a plurality of outlets fluidly coupled to the collector. The gas separation device includes a fluid flow path defined by the inlet, a space between the inner component and the outer housing, the collector, and a plurality of outlets, and a portion of the outer housing laterally aligned with the diffuser surface and disposed vertically above the diffuser surface is translucent or transparent.

[0036] In a thirty-third example ("Example 33"), the device of Example 32 further includes at least a portion of the core having a circular cross-section.

[0037] In a thirty-fourth example ("Example 34"), the device of Example 32 further includes at least a portion of the core having a rectangular cross-section. [Brief description of the drawings]

[0038] BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings are included to provide a further understanding of the disclosure, and are incorporated in and constitute a part of this specification, illustrate embodiments and, together with the description, serve to explain the principles of the disclosure.

[0039] [Figure 1] FIG. 1 is a flow diagram of a chromatography system according to some embodiments.

[0040] [Diagram 2] FIG. 2 illustrates a chromatography column for use with a gas separation device according to some embodiments.

[0041] [Diagram 3]FIG. 3 is a side view of multiple chromatography columns for use with a gas separation device according to some embodiments.

[0042] [Figure 3B] FIG. 3B is a side view of chromatography columns used with gas separation devices according to some embodiments.

[0043] [Figure 4] FIG. 4 is an expanded view of the gas separation device of FIG. 2, according to some embodiments.

[0044] [Diagram 5] FIG. 5 is an exploded view of the gas separation device of FIG. 4 according to some embodiments.

[0045] [Figure 6] FIG. 6 is a cross-sectional view of the gas separation device of FIG. 4 according to some embodiments.

[0046] [Figure 7] FIG. 7 shows a cross-sectional view of a flow profile of the gas separation device of FIG. 4 according to some embodiments.

[0047] [Figure 8] 8A-8F show schematic diagrams of a gas separation device according to some embodiments as gas bubbles are delivered therethrough.

[0048] [Figure 9] 9A-9F show schematic diagrams of a gas separation device according to some embodiments as gas bubbles are delivered therethrough.

[0049] [Figure 10] 10A-10F show cross-sectional views of flow profiles of gas separation devices according to some embodiments.

[0050] [Figure 11] FIG. 11 shows expected transition curves for various designs of the gas separation device described with reference to Example 1, according to some embodiments.

[0051] [Figure 12] FIG. 12 shows a step function representing the introduction of a salt solution into a gas separation device according to some embodiments.

[0052] [Figure 13] FIG. 13 shows the expected transition curve at the outlet of a gas separation device after introducing the salt solution shown in FIG. 12 according to some embodiments.

[0053] [Figure 14A] FIG. 14A shows a cross-sectional view of the design of gas separation device 23 described with reference to Example 1, according to some embodiments. [Figure 14B] FIG. 14B shows a cross-sectional view of the design of gas separation device 23 described with reference to Example 1, according to some embodiments. [Figure 14C] FIG. 14C shows a cross-sectional view of the design of gas separation device 23 described with reference to Example 1, according to some embodiments. [Figure 14D] FIG. 14D shows a cross-sectional view of the design of gas separation device 23 described with reference to Example 1, according to some embodiments. [Figure 14E] FIG. 14E shows a cross-sectional view of the design of gas separation device 23 described with reference to Example 1, according to some embodiments. [Figure 14F] FIG. 14F shows a cross-sectional view of the design of gas separation device 23 described with reference to Example 1, according to some embodiments. [Figure 14G] FIG. 14G shows a cross-sectional view of the design of gas separation device 23 described with reference to Example 1, according to some embodiments. [Figure 14H] FIG. 14H shows a cross-sectional view of the design of gas separation device 23 described with reference to Example 1, according to some embodiments. [Figure 14I]FIG. 14I shows a cross-sectional view of the design of gas separation device 23 described with reference to Example 1, according to some embodiments. [Figure 14J] FIG. 14J shows a cross-sectional view of the design of gas separation device 23 described with reference to Example 1, according to some embodiments. [Figure 14K] FIG. 14K shows a cross-sectional view of the design of gas separation device 23 described with reference to Example 1, according to some embodiments. [Figure 14L] FIG. 14L shows a cross-sectional view of the design of gas separation device 23 described with reference to Example 1, according to some embodiments. [Figure 14M] FIG. 14M shows a cross-sectional view of the design of gas separation device 23 described with reference to Example 1, according to some embodiments. [Figure 14N] FIG. 14N shows a cross-sectional view of the design of gas separation device 23 described with reference to Example 1, according to some embodiments. [Figure 14O] FIG. 14O shows a cross-sectional view of the design of gas separation device 23 described with reference to Example 1, according to some embodiments. [Figure 14P] FIG. 14P shows a cross-sectional view of the design of gas separation device 23 described with reference to Example 1, according to some embodiments. [Figure 14Q] FIG. 14Q shows a cross-sectional view of the design of gas separation device 23 described with reference to Example 1, according to some embodiments. [Figure 14R] FIG. 14R shows a cross-sectional view of the design of gas separation device 23 described with reference to Example 1, according to some embodiments. [Figure 14S] FIG. 14S shows a cross-sectional view of the design of gas separation device 23 described with reference to Example 1, according to some embodiments. [Figure 14T] FIG. 14T shows a cross-sectional view of the design of gas separation device 23 described with reference to Example 1, according to some embodiments. [Figure 14U] FIG. 14U shows a cross-sectional view of the design of gas separation device 23 described with reference to Example 1, according to some embodiments. [Figure 14V]FIG. 14V shows a cross-sectional view of the design of gas separation device 23 described with reference to Example 1, according to some embodiments. [Figure 14W] FIG. 14W shows a cross-sectional view of the design of gas separation device 23 described with reference to Example 1, according to some embodiments. [Fig. 14X] FIG. 14X shows a cross-sectional view of the design of gas separation device 23 described with reference to Example 1, according to some embodiments.

[0054] [Figure 15] 15A-15C show schematic diagrams of a gas separation device after the introduction of gas bubbles as described with reference to Example 2, according to some embodiments.

[0055] [Figure 16] FIG. 16 shows transition chromatograms related to the data in Table 2 of Example 2, according to some embodiments. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0056] Detailed Description Those skilled in the art will readily appreciate that the various aspects of the present disclosure may be implemented by any number of methods and devices configured to perform the intended functions. It should also be noted that the accompanying figures referenced herein are not necessarily drawn to scale and may be exaggerated to illustrate various aspects of the present disclosure, and in that respect, the figures should not be construed as limiting. The term "on" as used herein is understood to mean that an element, such as a polymeric film, is directly on top of another element, or that there may be intervening elements.

[0057] FIG. 1 shows a flow diagram of a liquid chromatography system 8 according to some embodiments. The liquid chromatography system 8 may be an affinity chromatography system for separating molecules from a liquid. However, the gas removal concepts described herein may utilize various other types of chromatography and related systems, including, but not limited to, column chromatography, ion exchange chromatography, diligand chromatography, adsorption columns, and gas chromatography. As shown, the liquid chromatography system 8 includes a fluid source 10, a first injector 12a and a second injector 12b, at least one pump 14, at least one detector 16, a collector 18, a waste stream 20, a data acquisition device 22, a gas separation device 24, and at least one chromatography device 26.

[0058] As shown, the fluid source 10 is configured to deliver the fluid mixture to the first injector 12a, which in turn delivers the fluid mixture to the pump 14. In some embodiments, the first injector 12a is configured to inject analytes and / or other molecules into the liquid delivered from the fluid source 10. The first injector 12a can inject these analytes and / or other molecules into the liquid before the liquid passes from the fluid source 10 to the pump 14. Additionally, in some embodiments, the second injector 12b is configured to inject analytes and / or other molecules into the fluid mixture after the fluid mixture is discharged from the pump 14. In some embodiments, the liquid chromatography system 8 includes both the first injector 12a and the second injector 12b, while in other embodiments, the liquid chromatography system 8 can include only one of the first injector 12a and the second injector 12b.

[0059] Additionally, the pump 14 is configured to pressurize the liquid chromatography system 8 and aid in delivering the fluid mixture from the fluid source 10 through the liquid chromatography system 8 in a desired direction through the liquid chromatography system 8 (e.g., either forward or reverse flow through the liquid chromatography system 8). In some embodiments, the liquid chromatography system 8 can include one pump 14, while in other embodiments, the liquid chromatography system 8 includes two or more pumps. As shown, the gas separation device 24 is fluidly coupled to the second injector 12b and the chromatography device 26. During operation of the liquid chromatography system 8, the fluid mixture is delivered through the gas separation device 24 to the chromatography device 26 or to the waste stream 20. As described further below, the gas separation device 24 assists in removing unwanted gases from the fluid mixture stream passing through the liquid chromatography system 8. The chromatography device 26 separates target analytes or molecules from the fluid mixture.

[0060] After passing through the chromatography device 26, the fluid mixture is delivered to a detector 16 configured to analyze the separated target analytes and / or other molecules of the fluid mixture, and the fluid mixture can be collected using a single collection vessel 18 or multiple collection vessels (not shown) while by-products or fluids of the solution that are not the target molecules can be delivered from the detector 16 to a waste stream 20. In the embodiment shown in FIG. 1, the liquid chromatography system 8 includes one detector 16, but in some embodiments, the liquid chromatography system 8 can include at least one detector 16. After passing through the detector 16, in some embodiments, information obtained from the detector 16 based on the characteristics of the fluid mixture can be sent to a data acquisition device 22. The data acquisition device 22 can be used to store and analyze the characteristics of the mixture passing through the chromatography device 26.

[0061] FIG. 2 shows an example of a chromatography apparatus 27 that can be used in combination with a chromatography device 26 of a liquid chromatography system 8. As shown, a housing 28 encloses a chromatography device 26 (not shown) having an inlet portion 30 and an outlet portion 32 extending from the housing 28. The inlet portion 30 is disposed opposite the outlet portion 32. A chromatography device, e.g., chromatography device 26, can define or confine a total volume. The total volume is defined by the volume between the inlet portion 30 and the outlet tube 34 (also referred to as the internal volume or fluid volume) of the chromatography device, e.g., chromatography device 26 (not shown). More specifically, this volume includes both the functional bed volume of the chromatography device, defined as the volume capable of containing or maintaining fluid during a separation process, and the volume of channels, tubes, or other connectors associated with the chromatography device.

[0062] While the chromatography device 26 and its features discussed herein are provided as examples, in some embodiments, the chromatography device 26 of the liquid chromatography system 8 can have a variety of other configurations based on the desired function and target process to be used. In some embodiments, the chromatography device 26 is similar to the chromatography device described in PCT / US21 / 049969, entitled "Affinity Chromatography Devices Comprising Fibrillated Polymer Membranes and Manifolds Comprising Same" by Clinger et al. In any case, the chromatography device 26 can include an inlet tube at the inlet portion 30. An outlet tube 34 can extend from and be fluidly connected to the outlet portion 32. Although the liquid chromatography system 8 and FIG. 2 are shown as including only one chromatography device 26, in some embodiments, multiple chromatography devices, such as the chromatography device 26, can be incorporated. For example, two or more chromatography devices, each having a similar or different configuration, can be incorporated as desired. The chromatography devices, including the chromatography device 26, can be coupled to each other at the inlet by a distributor or manifold, which can then be coupled to the gas separation device 24. In other words, gas separation device 24 can service one or more chromatography devices. Thus, although referred to herein as a single chromatography device, such as chromatography device 26, in some embodiments this can refer to multiple chromatography devices, such as chromatography device 26, coupled together at their inlets.

[0063] FIG. 3A illustrates such a variation of a chromatography device 26, which includes at least four chromatography devices within a housing 28 and is fluidly coupled to a gas separation device 24. More specifically, as illustrated, the chromatography device 26 includes a first manifold 6a connected to a first chromatography device 26a and a second chromatography device 26b, and a second manifold 6b connected to a third chromatography device 26c and a fourth chromatography device 26d. The manifolds 6 may be arranged in parallel in this manner. The ability to use at least two manifolds in parallel has the advantage of allowing for increased volumetric capacity while using the chromatography devices described herein. In other words, a configuration having multiple chromatography devices 26a-d eliminates the need to move to a chromatography device with a larger volume. Additionally, by arranging the manifolds in parallel as shown in FIG. 3A, concerns about overpressurizing the chromatography device 26 are alleviated. In further embodiments, the liquid chromatography system 8 may incorporate four or more chromatography devices.

[0064] Furthermore, in some embodiments, the liquid chromatography system 8 can incorporate more than one chromatographic device 26 in combination with more than one gas separation device 24. For example, FIG. 3B shows a further embodiment of a portion of the liquid chromatography system 8 (FIG. 1) in which the chromatographic device 26 includes a first chromatographic device 26a and a second chromatographic device 26b arranged in parallel. Each of the first and second chromatographic devices 26a, 26b is coupled to a gas separation device. Illustratively, the first chromatographic device 26a is fluidly coupled to the first gas separation device 24a, and the second chromatographic device 26b is fluidly coupled to the second gas separation device 24b. Additionally, the inlet tube 40a of the first gas separation device 24a and the inlet tube 40b of the second gas separation device 24b are each coupled to a first manifold 6a, such that fluid is delivered from the fluid source 10 (FIG. 1) through the manifold 6a and delivered in parallel to the gas separation devices 24a, 24b and the chromatography devices 26a, 26b. Similarly, the outlet portion 32a of the first chromatography device 26a and the outlet portion 32b of the second chromatography device 26b are fluidly coupled to a second manifold 6b, such that fluid is delivered through the chromatography devices 26a, 26b and then merged into a single fluid flow path. Although two gas separation devices are shown, any number of gas separation devices can be incorporated. For example, the liquid chromatography system 8 can include three or more gas separation devices and three or more chromatography devices for attachment to the gas separation devices.

[0065] FIG. 4 shows an expanded view of the gas separation device 24 coupled to an inlet portion 30 of a chromatography device (not shown) in a chromatography apparatus 27. The gas separation device 24 includes an inlet tube 40 coupled to an outer housing 50. As will be further described with reference to FIGS. 4-6, the inlet tube 40 and the outer housing 50 are configured to receive a fluid extending through the outer housing 50 and through at least one outlet 44 (FIG. 4). After passing through the at least one outlet 44, the fluid can be delivered to the chromatography device 26. More specifically, the at least one outlet 44 is coupled to the inlet portion 30 of the chromatography device 26, such that the gas separation device 24 and the chromatography device 26 are coupled in series with each other. More specifically, the at least one outlet 44 can be fluidly coupled to a channel and / or tube that is fluidly coupled to an inlet tube (not shown) of the chromatography device 26. In some embodiments, the at least one outlet 44 can be fluidly coupled to a channel that is fluidly coupled to a manifold, such as manifold 6A (FIG. 3A), to distribute the fluid to multiple chromatography devices 26. Additionally, in other embodiments, at least one outlet 44 may be directly coupled to a fitting and an inlet tubing of the chromatography device 26. The passage of fluid through the gas separation device 24 is further described herein with reference to Figures 5 and 6.

[0066] FIG. 5 illustrates an exploded view of the gas separation device 24. As illustrated, the gas separation device 24 includes an inlet tube 40 coupled to a top portion 42, an outer housing 50, an inner component 60 housed within the outer housing 50, a number of seals 66, and a connector ring 68 for use in assembling the gas separation device 24. The inlet tube 40 includes an opening 36 extending to a central portion 38. The central portion 38 couples to a top portion 42 that may define a portion of the outer housing 50 of the gas separation device 24. The inlet tube 40 may be defined as generally cylindrical such that the inlet tube 40 has a circular cross-section. However, various other configurations may be implemented, all of which are considered to be within the scope of the present disclosure. Additionally, the top portion 42 may be defined as circular or disk-shaped, as shown in the exemplary embodiment of FIG. 5, although various other configurations may be implemented. For example, in some embodiments, the inlet tube 40 and / or the top portion 42 may have a rectangular, triangular, or other applicable configuration. Additionally, the inlet tube 40 and the top portion 42 may be constructed from a transparent or translucent material. For example, the inlet tube 40 and / or the top portion 42 may be constructed from a transparent or translucent polymer, such as a cyclic olefin copolymer (COC) or an acrylic polymer. However, various other applicable transparent or translucent materials may be used to form the inlet tube 40 and / or the top portion 42. Transparent may be defined herein as allowing light to pass directly through the material. Translucent may be defined herein as allowing only a portion of light directed at the material to pass through the material. In some embodiments, the inlet tube 40 may not be transparent or translucent, while the top portion 42 is either transparent or translucent. In other embodiments, only a portion of the top portion 42 is transparent or translucent. Whether transparent or translucent, as described further herein, the material of the inlet tube 40 and / or the top portion 42 may be selected such that gas bubbles located vertically below the top portion 42 can be visually observed from outside the gas separation device 24 (e.g., with the naked eye under natural or artificial light).

[0067] With continued reference to FIG. 5, the inner component 60 will be further described. The inner component 60 includes an upper surface 62, also referred to herein as a diffuser surface, and a core 64 extending below the upper surface 62. As best shown in the cross-sectional view of FIG. 6, the upper surface 62 can include a longitudinal profile having a generally dome-shaped profile extending along a longitudinal axis L. A generally dome-shaped profile can be defined herein as the upper surface 62 having a dome-shaped or curved shape, with a maximum vertical height of the upper surface 62 generally located within the longitudinal center of the upper surface 62, and the vertical height of the upper surface 62 decreasing as the upper surface 62 extends outward from the longitudinal center. In other embodiments, the upper surface 62 can have a generally flat / planar longitudinal profile, as shown, for example, in the modified gas separation device 924 of FIG. 14H. In other words, the upper surface 62 can have a generally constant vertical height across the width and longitudinal extent of the upper surface 62. Additionally, various other longitudinal profiles may be incorporated, for example, frustoconical and / or conical longitudinal profiles may be implemented. However, regardless of the profile of the top surface 62, as shown in FIGS. 5 and 6, the top surface 62 of the inner component 60 extends to a vertical height that is lower than the lowest vertical height of the central portion 38 of the inlet tube 40. This is beneficial in that when fluids may be delivered in the reverse direction through the gas separation device 24, the fluids will exit the inlet tube 40 rather than being confined above the top surface 62 and near the inlet tube 40. Additionally, the core 64 may define a generally annular cross-sectional shape. However, various other configurations may be implemented. For example, the core 64 may be defined by a rectangular, triangular, elliptical, polygonal, or irregular shape. The above examples are not intended to be limiting, and any applicable shape of the core 64 may be incorporated into the gas separation device. Additionally, in some embodiments, a portion of the core 64 may have a first cross-sectional shape and another portion of the core 64 may have a second cross-sectional shape that is different from the first cross-sectional shape. In further embodiments, the core 64 may include more than two cross-sectional shapes.

[0068] Still referring to FIG. 5, the outer housing 50 of the gas separation device 24 will be further described. The outer housing 50 includes a base 52, a cavity 54 extending into the base 52 and abutting an outer wall 56, and at least one outlet 44 extending from a bottom of the base 52. Illustratively, the outer wall 56 includes a plurality of grooves 59 extending circumferentially into the outer wall 56 of the base 52 to accommodate a plurality of seals 66 and a connector ring 68. The outer housing 50 may be constructed of a polymeric material, such as polypropylene, polyetheretherketone (PEEK), cyclic olefin copolymer, polycarbonate, or any other suitable polymeric material. In other embodiments, the outer housing 50 may be constructed of a metallic material, or a variety of other applicable materials. The base 52 has a generally circular cross-section, although the base 52 may implement a variety of other shapes. Additionally, as illustrated, the plurality of seals 66 includes a first seal 66a and a second seal 66b housed in the groove 59 of the outer wall 56. In some embodiments, the plurality of seals 66 are O-ring seals, although various other types of seals could be implemented. Additionally, although the connector ring 68 is shown as having a generally C-shape, various other configurations and / or shapes of the connector ring 68 could be incorporated and are considered within the scope of the present disclosure.

[0069] The assembled gas separation device 24 is further described herein with reference to the cross-sectional view of FIG. 6. As shown, the inlet tube 40 is shown with the top portion 42 coupled to the base 52 of the outer housing 50. More specifically, the top portion 42 is coupled within a groove 59 in the wall 56 of the outer housing 50. As shown, the generally dome-shaped profile of the top portion 42 may match the generally dome-shaped profile of the top surface 62 of the inner component 60 to form an extended space between the top portion 42 and the top surface 62. A connector ring 68 engages the base 52 and is disposed above the top portion 42 to securely seat the top portion 42 within the base 52. A number of seals 66, illustratively O-ring seals, are used during assembly of the gas separation device 24 to ensure a fluid-tight seal within the gas separation device 24. Specifically, the seals 66 may contribute to a fluid-tight seal between the inner component 60, the top surface 62, and the base 52. Further, the inner component 60 is disposed within the cavity 54 such that the central axis C of the inner component 60 is aligned with the central axis D of the inlet tube 40. This allows the inner component 60 to be positioned away from the outer wall 56 of the base 52, forming a concentric space between the inner component 60 and the outer wall 56 of the base 52. In this manner, the core 64 of the inner component 60 can be defined with an annular shape. In other words, the inner component 60 is centrally disposed within the outer housing 50. However, in other embodiments, the central axis C of the inner component 60 can be laterally offset from the central axis D of the inlet tube 40. In this manner, fluid can flow through the space between the inner component and the inner surface of the outer housing 50.

[0070] Beneath the inner component 60, the base 52 includes a collector 58 defined as an area for joining the space extending between the inner component 60 and the outer wall 56 of the base 52. Additionally, extending from the collector 58 are at least one outlet 44, illustratively a first outlet and a second outlet 44a, 44b, which extend outwardly and can be coupled to an inlet portion of the chromatography device 26 (FIG. 3A). Although shown as two outlets 44a, 44b, the at least one outlet 44 can include one, two, three, four or more outlets. As will be further described with reference to FIGS. 6 and 7, the space between the upper surface 62 and the upper portion 42 in the inlet tube 40 and the space extending between the inner component 60 and the base 52 define a fluid flow path that allows fluid to pass through the gas separation device 24.

[0071] More specifically, with reference to the cross-sectional views of the fluid flow profile of device 24 in Figures 6 and 7, a fluid flow passage 70 is formed extending through gas separation device 24. Fluid flow passage 70 includes an inlet portion 72, a diffuser portion 74, a recombination portion 76, and an outlet portion 78. As shown, fluid flow passage 70 extends from opening 36 of inlet tube 40, down through central portion 38 of inlet tube 40, and into the space between upper surface 62 and upper portion 42. In this manner, inlet tube 40 defines inlet portion 72 of fluid flow passage 70 extending through inlet tube 40. As fluid flows through inlet portion 72 of fluid flow passage 70, the fluid defines a first average velocity μ1.

[0072] After extending through the inlet portion 72, the fluid flow passages 70 extend into the space between the top surface 62 and the outer housing 50. More specifically, the fluid extends vertically downward through the inlet portion 72, contacts the top surface 62 of the inner component 60, and diffuses laterally outward along the top surface 62. The fluid flow passages 70 thus define a diffuser portion 74 that extends vertically between the top surface 62 and the upper portion 42 and extends laterally within the outer housing 50. Within the diffuser portion 74, the velocity of the fluid passing through the fluid flow passages 70 decreases as the fluid flow impacts the top surface 62 and changes direction, and is defined by a second average velocity μ2.

[0073] Additionally, as shown, the fluid flow passage 70 can extend downwardly through the interval between the core 64 of the inner component 60 and the outer wall 56 of the base 52 of the outer housing 50. In this manner, fluid delivered through the fluid flow passage 70 is dispersed into multiple fluid flow passages and extends downwardly to the collector 58. In this manner, the fluid flow passage 70 can define a recombination portion 76 that extends from the top surface 62 of the inner component 60 to the bottom of the collector 58. In some embodiments, the recombination portion 76 is defined by an annular continuous interval that extends around the inner component 60. In other embodiments, the recombination portion 76 can be defined by a plurality of individual channels that extend around the core 64 of the inner component 60.

[0074] Due to the concentric configuration of the inner component 60 and the base 52 of the outer housing 50, any fluid flow paths through which fluid may pass around the periphery of the inner component 60 have the same distance from the top surface 62 and the collector 58. This allows the fluid flow to maintain plug flow through the fluid flow paths 70, ensuring that fluid molecules that were pre-grouped before contacting the top surface 62 recombine at the collector 58. In other words, the configuration of the inner component 60 allows for fluid flow that reduces the amount of mixing within and / or between the fluids.

[0075] As shown, once the fluid has passed through the collector 58, the fluid can extend to at least one outlet 44 to exit the gas separation device 24. Thus, the fluid flow path 70 defines an outlet portion 78 that extends vertically between the bottom of the collector 58 and the exterior of the gas separation device 24.

[0076] Each of the above-mentioned portions of the fluid flow path 70 is defined by a fluid flow path volume, which is also referred to herein as the hold-up volume of the gas separation device 24. In other words, both the fluid flow path volume and the hold-up volume are measured as the fluid flow volume extending through the gas separation device 24, and the fluid flow volume is the sum of the volumes of the above-mentioned portions of the fluid flow path 70. For example, the inlet portion 72 includes an inlet partial volume defined by the volume of the inlet portion 72 that can hold fluid. Furthermore, the amount of space defined between the upper surface 62 and the upper portion 42 defines a diffuser volume of the diffuser portion 74. Similarly, the volume of the space between the upper surface 62 and the bottom of the collector 58 defines a recombination partial volume. Finally, the volume of at least one outlet 44, illustratively the sum of the volumes of the outlets 44a and 44b, defines an outlet partial volume. As previously mentioned, the fluid flow path volume is defined by the sum of the inlet partial volume, the diffuser partial volume, the recombination partial volume, and the outlet partial volume, respectively. In some embodiments, the inlet partial volume and the diffuser partial volume together are between 10% and 75% of the fluid flow path volume. Further, the inlet partial volume and the diffuser partial volume together can be between 35% and 50% of the fluid flow path volume. However, various other volume ratios between the various portions of the fluid flow path 70 can also be incorporated. For example, the outlet partial volume can be between 5% and 75% of the fluid flow path volume. In further embodiments, the outlet partial volume can be between 10% and 50% of the fluid flow path volume.

[0077] As will be further described with reference to the test methods and examples, the gas separation device 24 is configured such that, if there is a volume of air bubbles contained within the fluid delivered in a forward direction through the fluid flow path 70, as the fluid passes through the diffuser portion 74, the volume of air bubbles will be trapped within the diffuser portion 74 and between the upper surface 62 and the upper portion 42. The forward direction is defined as the direction in which the fluid extends from the inlet portion 72 to the outlet portion 78. As the fluid flows through the fluid flow path 70 in this direction, the volume of air bubbles will remain trapped within the diffuser portion 74. An operator can activate the liquid chromatography system 8 to reverse the fluid flow through the gas separation device 24 and the chromatography device 26. More specifically, an operator can interact with a user interface utilized to send commands to components of the liquid chromatography system 8 (FIG. 1) to activate the liquid chromatography system 8 to stop the forward fluid flow through the gas separation device 24 and then reverse the fluid flow through the gas separation device 24 such that the fluid is delivered through the gas separation device 24 from the outlet portion 78 to the inlet portion 72. The reverse flow through the fluid flow path 70 causes at least a portion of the volume of gas bubbles to exit through the inlet tube 40 of the gas separation device 24. Thus, the fluid reversal causes at least a portion of the volume of gas bubbles trapped within the diffuser portion 74 to exit through the inlet tube 40 along with the fluid. In this operating condition, fluid is delivered from the gas separation device 24 to the waste stream 20, ensuring that gas bubbles exit the liquid chromatography system 8 and are not reintroduced into the gas separation device 24.

[0078] At least the top portion 42 is transparent or translucent so that an operator can visualize the volume of trapped gas bubbles within the diffuser portion 74 and can visualize the removal of the volume of gas bubbles from the diffuser portion 74. In this manner, an operator can monitor the gas separation device 24 and can stop and reverse the flow once a desired volume of trapped gas bubbles is visualized within the gas separation device 24. For example, in some embodiments, an operator can monitor the gas separation device 24 and stop the flow when the volume of gas bubbles reaches a maximum bubble volume, which may be defined as at least 95% of the volume of the diffuser portion 74. Additionally, fluid can be delivered in reverse flow for various amounts of time controlled by the operator. For example, the fluid flow can be reversed until at least 1% to 100% of the volume of trapped gas is removed from the diffuser portion 74. In some embodiments, the fluid flow is operated in the reverse direction until at least 25% of the volume of gas bubbles is removed from the diffuser portion 74.

[0079] The operator can subsequently stop the fluid flow and actuate the fluid to flow in the forward direction again. When this occurs, the inlet tube 40 is reconnected to the fluid source, such as fluid source 10 (FIG. 1), and the outlet 44 is coupled to an inlet portion (not shown) of the chromatography device 26, delivering the fluid through the gas separation device 24 to the chromatography device 26.

[0080] As discussed above, the gas separation device 24 provides the advantage of efficiently trapping air bubbles within the gas separation device 24 and easily reversing the fluid flow to remove trapped air bubbles from within the gas separation device 24. As further described with reference to the test methods and examples, the air bubble trapping capability of the gas separation device 24 can be quantified by the Air Trap Effectiveness Ratio (ATER). The ATER is calculated by dividing the ratio of the second average velocity μ2 to the first average velocity μ1 by the diffuser fractional volume. The gas separation device 24 is configured such that the ATER is approximately 0.001 mL while fluid is flowing forward through the gas separation device 24. -1 ~about 0.51mL -1When the ATER is maintained within the above range, the gas separation device 24 can capture air bubbles from fluid passing through the fluid flow passage 70, trap the air bubbles within the diffuser portion 74, and release the air bubbles upon backflow of fluid through the fluid flow passage 70.

[0081] A further advantage of the gas separation device 24 is that the transition volume of the fluids delivered through the gas separation device 24 and / or the chromatography device 26 is reduced. More specifically, when a first fluid is inserted through the gas separation device 24 and then a second fluid is delivered to the gas separation device 24, the transition volume is the volume through which the two fluids flow until the first fluid is no longer detected. As further described with reference to the test methods and examples, the gas separation device 24 can exhibit a transition volume of about 5 times or less the value of the fluid flow path volume of the gas separation device 24. In some embodiments, the transition volume can be 5 times or less the value of the fluid flow path volume. Furthermore, when calculated based on the transition volume of the flow through both the gas separation device 24 and the chromatography device 26, the transition volume can be 5 times or less the combined volume of the gas separation device 24 and the chromatography device 26. A further advantage of the gas separation device 24 is that the device 24 is configured such that the fluid flow volume of the gas separation device 24 is 50% or less of the combined volume of the chromatography device 26. For example, in some embodiments, the fluid flow volume of gas separation device 24 can be about 1% to 50% of the total volume of chromatography device 26. However, various other ratios of fluid flow volume of gas separation device 24 to chromatography device 26 may be implemented.

[0082] Those skilled in the art will readily appreciate that the various aspects of the present disclosure may be implemented by any number of methods and devices configured to perform the intended functions. It should also be noted that the accompanying figures referenced herein are not necessarily drawn to scale and may be exaggerated to illustrate various aspects of the present disclosure, and in that regard, the figures should not be construed as limiting.

[0083] Test Method How to simulate liquid flow through a device A computational fluid dynamics (CFD) model was developed with a commercially available solver. The fluid flow solver is based on the finite volume method, where the flow domain is divided into small volumes, also called cells, and the governing equations are solved at the centroid of each cell. The governing equations are further explained and discussed herein. By solving the governing equations, the three directional fluid velocities, fluid pressures, salt concentrations, and turbulence variables are calculated at each cell. As mentioned above, FIG. 6 shows a cross-sectional view of a gas separation device 24 including fluid flow paths modeled with computational fluid dynamics (CFD), while FIG. 7 shows a cross-sectional view of a gas separation device 24 including schematic fluid domains of the gas separation device 24. Since the testing method herein is described with reference to the gas separation device 24, other embodiments of the gas separation device 24 are simulated using computational fluid dynamics.

[0084] The fluid flow field was calculated by solving the Reynolds-averaged Navier-Stokes equations, including the conservation of mass and momentum. A shear stress transport k-omega model was used to predict the turbulent flow of fluid through the fluid flow passage.

[0085] The mass conservation and momentum equations are written as follows:

number

number

[0086] A constant mass flow rate was defined at the inlet portion 72 of the gas separation device 24 (Figures 6-7). The outlet was fixed at zero gauge pressure. Incompressible assumptions were assumed for the liquid and ideal gas for the air. The properties used for the method include those of water and air in the liquid and gas phases, respectively. The density of the liquid is 997.561 kg / m 3 , and the viscosity was set to 8.8871 Pa·s. Interfacial forces are modeled as volume forces using the continuum surface force (CSF) approach of Brackbill et al. (Brackbill, JU, Kothe, DB and Zemach, C. 1992. Continuum methods for modeling surface tension. J. Comp. Physics, 100, pp. 335-354). The surface tension constant between liquid and gas was fixed at 0.072 N / m. However, a variety of other surface tension and density values ​​can be used to model the required fluid and material properties.

[0087] Method for simulating the behavior of air bubbles passing through a device and determining air entrapment effectiveness parameters in the simulation A volume of fluid (VOF) multiphase model is used to predict the air and liquid interfaces within the gas separation device 24. The distribution of the phases (air and liquid) and the location of the interfaces are described by fields of phase volume fractions αi, which are given by: where Vi is the volume of phase i in the cell and V is the volume of the cell.

number

[0088] The volume fractions of all phases within a cell must sum to 1, as shown in the following equation, where N is the total number of phases.

number

[0089] Fluids present in cells containing the same interface are treated as a mixture with volume-averaged properties.

[0090] The results of simulating the liquid flow through the device are used as the initial conditions for the bubble simulation. Initially, there is only water passing through the gas separation device 24 at a fixed flow rate. Then, a fixed volume of gas bubbles is injected at the inlet portion 72 of the gas separation device 24.

[0091] Gas bubbles are trapped by volume expansion within the simulated gas separation device 24. Such expansion affects fluid flow properties such as velocity, pressure drop, residence time, mixing, drag and surface tension.

[0092] To predict the performance of the design, the following parameters are introduced:

number

[0093] where u2 is the average fluid velocity in the diffuser section 74, u1 is the average fluid velocity in the inlet section 72, and V is the volume of the diffuser section 74.

[0094] The bubble trapping performance decreases with increasing air trapping effectiveness ratio (ATER). When the ATER is higher than a critical value, the bubbles pass through the gas separation device 24. The ATER can be decreased by increasing the volume of the diffuser section 74. However, decreasing the ATER below the critical value does not affect the bubble trapping performance.

[0095] For example, Figures 8A-8F show that ATER is approximately 0.938 mL over the simulated time conditions. -18A-8F, a fluid flows through the fluid flow passages 70 of the gas separation device 24 and a gas bubble 80 is delivered into the system, but the gas bubble 80 travels throughout the gas separation device 24 and is not trapped within the diffuser portion 74 of the gas separation device 24. Specifically, FIG. 8A shows a simulation at a time point about 0.1 seconds after the gas bubble 80 is delivered into the inlet portion 72. FIG. 8B shows a simulation of the gas separation device 24 at a time point about 0.2 seconds after the gas bubble 80 is delivered into the inlet portion 72. As shown in FIGS. 8A-8F, the gas bubble 80 is disposed within the diffuser portion 74. Additionally, FIG. 8C shows a simulation at a time point about 0.3 seconds after the gas bubble 80 is delivered. As shown, the gas bubble has passed through the diffuser portion 74 and traveled to the recombination portion 76. Figures 8D and 8E show an air bubble 80 disposed within the diffuser portion 74, recombination portion 76, and outlet portion 78 of gas separation device 24. Figure 8F shows the system at approximately 0.1 seconds after air bubble 80 is delivered to inlet portion 72, at which point air bubble 80 has passed throughout gas separation device 24. Thus, Figures 8A-8F show air bubble 80 passing throughout gas separation device 24, rather than being trapped within diffuser portion 74.

[0096] 9A to 9F show a method for simulating the gas separation device 24, in which the ATER is about 0.116 mL -19F. As shown, gas bubbles 80 are delivered with the fluid into gas separation device 24 and are trapped within diffuser portion 74. Specifically, in FIG. 9B, the fluid and gas bubbles 80 are shown extending into diffuser portion 74. As fluid continues to pass through gas separation device 24, in FIGS. 9C-9F, the gas bubbles 80 are shown remaining trapped within diffuser portion 74 and not extending downward into gas separation device 24. This is desirable for proper functioning of gas separation device 24 so that gas bubbles 80 are not delivered into chromatography device 26 (FIG. 2).

[0097] How to simulate flow transitions of salt solutions through a device Salt was introduced into the flow field as a tracer, and the movement of the salt within the gas separation device 24 was tracked by solving the convection-diffusion equation.

number

[0098] In the above formula, c, u and D ij are the salt concentration in the fluid, the fluid velocity and the salt diffusivity, respectively. In the above model formulation, it is assumed that the fluid properties are not modified by the salt. The salt was introduced as a step function at the inlet boundary.

[0099] 10A-10F show a CFD model of the gas separation device 24 as salt solution is modeled being inserted through the fluid flow paths 70. Specifically, FIG. 10A shows the gas separation device 24 before the salt solution is inserted. FIG. 10B shows the CFD model of the gas separation device 24 as salt solution is inserted into the inlet portion 72 of the gas separation device 24. Additionally, FIGS. 10C-10D show further salt solution being inserted through the fluid flow paths 70 of the gas separation device 24, also showing mixing of the fluids. As the insertion of salt solution continues over time, as shown in FIGS. 10E and 10F, mixing decreases and the fluid flow paths 70 are completely consumed with salt solution.

[0100] This method can be applied to several different designs of devices by varying the parameters built into the model. Furthermore, the model allows the determination of the transition curve, as shown in FIG.

[0101] Specifically, FIG. 11 shows the expected transition curves for three different designs of gas separation device 24. More specifically, design 1 corresponds to gas separation device 24 as shown in FIG. 14A and has transition curve D, design 9 corresponds to modified gas separation device 1024 as shown in FIG. 14I showing transition curve E, and design 14 corresponds to modified gas separation device 1524 in FIG. 14N corresponding to transition curve F. The transition curves show the relationship between the conductivity of the solution versus the volume of the solution flowing, showing the transition volume for each design. As shown, the simulated gas separation devices of designs 1 and 14 achieve steady-state conductivity in a volume less than that required for design 9. The steady-state conductivity can be a set conductivity selected based on the conductivity of the second fluid that is simulated to be delivered through gas separation device 24. This corresponds to the smaller transition volume of the simulated gas separation device of designs 1 and 14 compared to the transition volume of the simulated gas separation device of design 9.

[0102] How to determine the volume to complete a simulated salt solution flow transition through a device Increasing the fluid flow channel volume of the gas separation device can decrease the ATER, but it increases the transition volume of the gas separation device. A high transition volume is undesirable for chromatography applications. Increasing the transition volume of the device can increase the solution consumption and reduce the efficiency of the process. To actually measure the transition volume of a gas separation device, a transition test is usually performed. A transition experiment involves pushing one fluid out of the gas separation device by introducing a new fluid. Thus, a transition simulation was performed using a step function by introducing a salt solution at the inlet boundary, as shown in Figure 12. Figure 13 shows the expected transition curve at the outlet of the simulated gas separation device. The conductivities of the salt solution and water were set to 21.5 and 0.01 mS / cm, respectively. The transition volume was measured when the outlet conductivity reached 21 mS / cm, which was determined as the steady-state conductivity.

[0103] Experimental verification of air capture effectiveness Gas separation device 24 was physically constructed from Design 1 in Table 1 and is referred to herein as Gas Separation Device A. Gas separation device A, mounted on top of a spiral wound manifold affinity chromatography device as described in PCT Application No. PCT / US21 / 049969 to Clinger et al., was placed in an AKTA Pilot liquid chromatography system (Cytiva, Marlborough, Massachusetts) and phosphate buffered saline (PBS) was pumped through gas separation device A and the spiral wound manifold affinity chromatography device at a flow rate of 696 mL / min. Air bubbles were introduced into gas separation device A by removing the feed tube from the PBS buffer, and approximately 1 second after the tube was removed, the feed tube was returned to the PBS buffer. A few seconds after the air bubbles were trapped in gas separation device A, the pump of the liquid chromatography system was reversed, expelling the air bubbles into the waste stream along with a small amount of PBS.

[0104] Experimental method for determining the transition volume An affinity chromatography device 26, described in PCT Application No. PCT / US21 / 049969 to Clinger et al., was placed in an AKTA Pilot liquid chromatography system (Cytiva, Marlborough, Massachusetts) with or without a gas separation device A attached to the inlet of the affinity chromatography device. Phosphate buffered saline (PBS) was pumped through the device at a flow rate of 152 mL / min, followed by deionized water at a flow rate of 152 mL / min. The transition volume was reported as the amount of volume (normalized to column volume) required to flow through the affinity chromatography device with or without a gas separation device A attached to the inlet of the affinity chromatography device until a conductivity of 0.15 mS / cm was reached at the outlet of the device. This conductivity indicates a complete volume transition from PBS to water. The column volume is defined as the total volume of the chromatography device 26 (FIG. 2). EXAMPLES

[0105] example Example 1: Computational Fluid Dynamics (CFD) simulation results A total of 24 unique modified designs of gas separation device 24 (FIG. 3) were generated and the flow performance was simulated using the test methodology described above. FIGS. 14A-14X show cross-sectional views of simulated designs 1-24, respectively. Specifically, FIG. 14A shows a cross-sectional view of gas separation device 24. FIG. 14B shows a modified gas separation device 324 having a fluid flow path 370 with a straight-shaped recombination portion 376 and no indents in the recombination portion 376. FIG. 14C shows a modified gas separation device 424 defining a fluid flow path 470 with a uniform diffuser portion 474 and a straight recombination portion 476. Additionally, FIG. 14D shows a modified gas separation device 524 having a modified fluid flow path 570 with a thinner diffuser portion 574 such that the volume of diffuser portion 574 is smaller than the volume of diffuser portion 74 (FIG. 14A). 14E shows a modified gas separation device 624 having a modified fluid flow path 670 that extends linearly downward and has a recombination portion 674 followed by a laterally extending portion. Additionally, FIG. 14F shows a modified gas separation device 724 with a modified fluid flow path 770 that has a recombination portion 776 that extends linearly and laterally from a corner where it joins with a diffuser portion 774 of the gas separation device 724.

[0106] Referring to FIG. 14G, a modified gas separation device 824 is shown having a similar design to that shown in FIG. 14E. FIG. 14H shows an additional modified gas separation device 924 with modified fluid flow paths 970, with a top surface similar to top surface 62 (FIG. 1) having a straight, flat profile, and a bottom diffuser portion 974 having a flat profile. Additionally, the volume of the diffuser portion 974 is shown to be larger than the volume of the diffuser portion 74 of the gas separation device. Additionally, referring to FIG. 14I, a modified gas separation device 1024 is shown having modified fluid flow paths 1070. The modified fluid flow paths 1070 are similar to the fluid flow paths 470 of the gas separation device 424, but the diffuser portion 1074 has a larger volume. Referring to FIG. 14J, a modified gas separation device 1124 is shown having a modified flow profile 1170, with the diffuser portion 1174 having a diameter that is approximately 90% of the diameter of the diffuser portion 74 of the gas separation device 24. Additionally, Figure 14K illustrates a modified gas separation device 1224 in which the diameter of diffuser portion 1274 is about 80% of the diameter of diffuser portion 74, Figure 14L illustrates a modified gas separation device 1324 in which the diameter of diffuser portion 1374 is about 70% of the diameter of diffuser portion 74, and Figure 14M illustrates a modified gas separation device 1424 in which the diameter of diffuser portion 1474 is about 60% of the diameter of diffuser portion 74. Additionally, Figure 14N illustrates a gas separation device 1524 in which the diameter of diffuser portion 1574 is about 50% of the diameter of diffuser portion 74.

[0107] FIG 14O shows a modified gas separation device 1624 having a diffuser portion 1674 with a diameter that is 50% of the diameter of diffuser portion 74 and an increased thickness. FIG 14P shows a modified gas separation device 1724 similar to diffuser portion 1674 (FIG 14O), but with a diffuser portion 1774 that is thicker than the thickness of diffuser portion 1674. Similarly, FIG 14Q and FIG 14R show modified gas separation devices 1824, 1924 with increased thicknesses of diffuser portions 1874, 1974, respectively. Additionally, FIG 14S and FIG 14T show modified gas separation devices 2024, 2124 with diffuser portions 2074, 2174 with different thicknesses and diameters, respectively. Similarly, Figures 14U, 14V and 14W show additional modified gas separation devices 2224, 2324 and 2424 having diffuser sections 2274, 2374 and 2474, respectively, with different thicknesses and diameters.

[0108] FIG. 14X shows a modified gas separation device 2524 with a similar design to FIGS. 14F and 14G, but with an overall diameter approximately twice as large as that of FIGS. 14F and 14G, a curved recombination section 2576, and a larger diffuser section 2574.

[0109] A simulated delivery of air bubbles through each of the above models was performed. The simulation results are shown in Table 1. The result was an air trapping effectiveness ratio (ATER) of 0.51 mL. -1 It was indicated that the gas bubbles had passed through the respective gas separation device when the pressure exceeded 100 MPa. [Table 1]

[0110] Example 2: Experimental verification of air entrapment effectiveness and transition volume A series of time lapse diagrams taken from still photographs shown in Figures 15A-15C demonstrated that air bubbles introduced into gas separation device A can be visualized and removed using the appropriate test methodology described above. As shown in Figure 15A, prior to the insertion of the air bubbles, fluid flows through gas separation device A and no air bubbles are shown trapped in diffuser portion 74. However, during the insertion of air bubbles 80, air bubbles 80 are shown within diffuser portion 74 (see Figure 15B) and can be observed from the exterior of gas separation device A. Furthermore, after the fluid flow through gas separation device A is reversed, the air bubbles are no longer visible within diffuser portion 74 and have been expelled from gas separation device A, as shown in Figure 15C.

[0111] The transition volumes with and without gas separation device A in the flow path of the chromatography device are shown in Table 2 and are determined using the test method described above. The difference in transition volume is small, indicating that the impact of gas separation device A on the transition volume is negligible. As shown in Table 2, the transition volume of the system with and without gas separation device A remains less than 5 times the column volume. The transition chromatograms associated with the data in Table 2 are shown in Figure 16. [Table 2]

[0112] Those skilled in the art will readily appreciate that various aspects of the disclosure may be implemented by any number of methods and devices configured to perform the intended functions, and it should be noted that the examples and methods herein should not be construed as limiting.

Claims

1. 1. A gas separation device comprising: a housing defining a fluid flow path between an exterior surface and an interior surface, the housing having an inlet in communication with the fluid flow path and an outlet in communication with the fluid flow path, the housing operable to permit fluid flow in a forward direction from the inlet to the outlet and a reverse direction from the outlet to the inlet, the fluid flow path defining a fluid flow path volume; an inlet portion positioned to receive fluid from the inlet during forward fluid flow through the housing; a diffuser portion positioned to receive fluid from the inlet portion during forward fluid flow through the housing; a recombination portion positioned to receive fluid from the diffuser portion during forward fluid flow through the housing; an outlet portion positioned to receive fluid from the recombination portion during forward fluid flow through the gas separation device, wherein the outlet portion defines an outlet portion volume; Including, the inlet portion defines an inlet subvolume; the diffuser portion defines a diffuser portion volume; the recombination portion defines a recombination portion volume; The gas separation device is configured to separate 0.001 mL of gas from the gas during forward fluid flow through the housing. －１ ~0.51mL －１ The gas separation device is configured to exhibit an Air Capture Effectiveness Ratio (ATER) where ATER is:

2. The gas separation device of claim 1 , configured to exhibit a transition volume during forward fluid flow through the housing that is no greater than 5 times the value of the fluid flow path volume.

3. The gas separation device of claim 1 further comprising a fluid flow path exiting said outlet.

4. The gas separation device of claim 1 , further comprising a manifold in fluid communication with the outlet, the manifold dividing fluid exiting the outlet into a plurality of fluid flow paths.

5. The gas separation device of claim 4 , wherein the plurality of fluid flow paths includes at least two fluid flow paths.

6. The gas separation device of claim 1 , wherein the inlet partial volume and the diffuser partial volume together are between 10% and 75% of the fluid flow path volume.

7. 2. The gas separation device of claim 1, wherein a first average fluid velocity used to determine ATER is defined by a velocity of fluid flowing through the inlet and a second average fluid velocity used to determine ATER is defined by a velocity of fluid flowing through the diffuser section.

8. 8. The gas separation device of claim 7, wherein ATER is defined by the ratio of said second average fluid velocity to said first average fluid velocity divided by said diffuser partial volume.

9. The gas separation device of claim 1 , wherein at least one of the inner and outer surfaces of the diffuser portion defines a generally dome-shaped longitudinal profile.

10. The gas separation device of claim 1 , wherein at least one of the inner and outer surfaces of the diffuser portion defines a generally flat longitudinal profile.

11. The gas separation device of claim 1 , wherein at least one of the inner and outer surfaces of the diffuser portion defines a conical or frustoconical profile.

12. The gas separation device of claim 1 , wherein at least a portion of the housing is translucent or transparent, whereby the gas volume within the diffuser portion is visible through the housing.

13. The gas separation device of claim 1 , wherein the recombination portion is defined by a plurality of individual channels extending between an inner surface and an outer surface of the fluid flow path.

14. The gas separation device of claim 1 , wherein the recombination portion is defined by an annular channel extending between an inner surface and an outer surface of the fluid flow path.

15. The gas separation device of claim 1 , wherein the recombination portion is defined by inner and outer surfaces of fluid flow channels having a concentric circular configuration.

16. A gas separation device having a housing defining a fluid flow path between an exterior surface and an interior surface, the housing having an inlet in communication with the fluid flow path and an outlet in communication with the fluid flow path, the housing operable to permit forward and reverse fluid flow from the inlet to the outlet. a fluid source coupled to the inlet of the gas separation device; and at least one chromatography device comprising an inlet coupled to said outlet of said gas separation device; Including, the fluid flow path defines a fluid flow path volume; the fluid source is configured to deliver a forward flow through the gas separation device and the chromatography device, the chromatography device being operable to allow a reverse flow through the chromatography device; The gas separation device is adapted to separate gases from one another by up to 0.001 mL during forward flow through the housing. －１ ~0.51mL －１ The fluid system is configured to exhibit an Air Capture Effectiveness Ratio (ATER) of:

17. 17. The system of claim 16, wherein a first average fluid velocity used to determine ATER is defined by a velocity of fluid flowing through the inlet, a second average fluid velocity used to determine ATER is defined by a velocity of fluid flowing through the diffuser portion, and ATER is defined by a ratio of the second average fluid velocity to the first average fluid velocity divided by a volume of the diffuser portion.

18. 17. The system of claim 16, wherein the chromatography device has a total volume defined by the volume between a fluid inlet of the chromatography device and a fluid outlet of the chromatography device, and the fluid flow volume of the gas separation device is less than or equal to 50% of the total volume of the chromatography device.

19. 17. The system of claim 16, wherein the gas separation device is configured to exhibit a transition volume during forward flow through the housing that is no greater than 5 times the value of a fluid flow path volume of the gas separation device.

20. 17. The system of claim 16, wherein the gas separation device further comprises a manifold in fluid communication with at least one outlet, the manifold dividing fluid exiting the outlet into a plurality of fluid flow paths.

21. 17. The system of claim 16, wherein the fluid flow path includes an inlet portion disposed to receive fluid from the inlet during forward flow through the housing, a diffuser portion disposed to receive fluid from the inlet portion during forward flow through the housing, a recombination portion disposed to receive fluid from the diffuser portion during forward flow through the housing, and an outlet portion disposed to receive fluid from the recombination portion during forward flow through the gas separation device, the diffuser portion defining a diffuser portion volume.

22. 22. The system of claim 21, wherein at least a portion of one or both of an inner and outer surface of the fluid flow passage defining the diffuser portion is translucent or transparent such that air bubbles can be observed within the diffuser portion.

23. 1. A method of trapping and releasing a volume of gas bubbles in a gas separation device, the gas separation device having a housing defining a fluid flow path having an exterior surface and an interior surface, the housing having an inlet in fluid communication with the fluid flow path and an outlet in fluid communication with the fluid flow path, the method comprising: delivering fluid in a forward direction through the flow path such that fluid flows through the gas separation device from the inlet to the outlet; trapping said volume of gas within said gas separation device; ceasing delivery of fluid through the fluid flow path; and delivering fluid in a reverse direction through the fluid flow path such that fluid flows from the outlet to the inlet to remove at least a portion of the volume of gas bubbles from the gas separation device; Including, At least a portion of at least one of the interior and exterior surfaces of the housing is translucent to allow observation of the volume of gas.

24. 24. The method of claim 23, wherein the fluid flow path includes an inlet portion disposed to receive fluid from the inlet during forward fluid flow through the housing, a diffuser portion disposed to receive fluid from the inlet portion during forward flow through the housing, a recombination portion disposed to receive fluid from the diffuser portion during forward flow through the housing, and an outlet portion disposed to receive fluid from the recombination portion during forward flow through the gas separation device, the diffuser portion defining a diffuser portion volume.

25. 25. The method of claim 24, wherein trapping the volume of gas bubbles comprises trapping the volume of gas bubbles within the diffuser portion of the gas separation device.

26. 24. The method of claim 23, further comprising the step of reversing the flow when the bubble volume approaches a maximum bubble volume defined by about 95% of the diffuser subvolume.

27. 24. The method of claim 23, further comprising delivering fluid through the fluid flow path in a forward direction from the inlet to the outlet of the housing after a portion of the volume of bubbles has exited the gas separation device.

28. The gas separation device is adapted to separate gases from one another by up to 0.001 mL during forward flow through the housing. －１ ~0.51mL －１ 24. The method of claim 23, wherein the air capture effectiveness ratio (ATER) is:

29. 24. The method of claim 23, wherein the gas separation device exhibits a transition volume during forward flow through the housing that is less than or equal to 5 times the value of the fluid flow path volume.

30. The method of claim 24, wherein the volume of bubbles is between 1% and 100% of the fluid flow path volume.

31. 24. The method of claim 23, wherein the outlet of the gas separation device is fluidly connected to an inlet of a chromatography device, whereby the gas separation device and the chromatography device are arranged in series, and the method further comprises delivering fluid through the outlet of the gas separation device to the inlet of the chromatography device.

32. Outer housing, an inlet coupled to the outer housing; an inner component disposed within the outer housing and defining a diffuser surface and a core; a collector disposed below the inner component; and a plurality of outlets fluidly coupled to the collector; a fluid flow path defined by the inlet, a spacing between the inner component and the outer housing, the collector, and the plurality of outlets; A gas separation device comprising: the diffuser surface has a generally dome-shaped longitudinal profile; A gas separation device, wherein a portion of the outer housing laterally aligned with and vertically above the diffuser surface is translucent or transparent.

33. 33. The gas separation device of claim 32, wherein at least a portion of the core has an annular cross-section.

34. 33. The gas separation device of claim 32, wherein at least a portion of the core has a rectangular cross-section.

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