Gas separation device

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 This disclosure generally relates to gas separation devices and methods, and more specifically to gas separation devices and methods for use with liquid chromatography systems. [Background technology]

[0002] background Liquid chromatography is generally used to separate and / or purify target molecules, 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 to the target molecule is bound. Upon contact with the ligand, the target molecule binds to the matrix and is therefore removed from the fluid mixture.

[0003] Bubbles can be introduced into the system during the delivery of fluids containing target molecules, as well as other fluids used in chromatography devices. The introduction of bubbles generally negatively impacts the function of liquid chromatography devices, and it is desirable to minimize these occurrences. [Overview of the project]

[0004] Abstract In the first example ("Example 1"), the gas separation device includes a housing that defines a fluid passage between an outer surface and an inner surface, the housing having an inlet communicating with the fluid passage and an outlet communicating with the fluid passage, and the housing is operable to allow fluid flow in the forward direction from the inlet to the outlet and in the reverse direction from the outlet to the inlet. The fluid passage includes an inlet portion that defines the fluid passage volume and is arranged to receive fluid from the inlet during a forward fluid flow through the housing, wherein the inlet portion defines the inlet portion volume; a diffuser portion that defines the diffuser portion volume and is arranged to receive fluid from the inlet portion during a forward fluid flow through the housing, wherein the diffuser portion defines the diffuser portion volume; a recombination portion that defines the recombination portion volume and is arranged to receive fluid from the recombination portion during a forward fluid flow through the housing; and an outlet portion that defines the outlet portion volume and is arranged to receive fluid from the recombination portion during a forward fluid flow through the gas separation device. The gas separation device allows 0.001 mL of fluid to flow through the housing in the forward direction. -1 ~0.51mL -1 It is configured to exhibit an effective air capture ratio (ATER).

[0005] In the second example ("Example 2"), the device of Example 1 is configured such that the gas separation device exhibits a transition volume of no more than five times the value of the fluid flow path volume during the forward fluid flow through the housing.

[0006] In the third example ("Example 3"), the device of Example 1 further includes a fluid channel through which the gas separation device exits the outlet.

[0007] In the fourth example ("Example 4"), the device of Example 1 further includes a manifold in which the gas separation device is in fluid communication with the outlet, the manifold includes dividing the fluid exiting the outlet into a plurality of fluid passages.

[0008] In the fifth example ("Example 5"), the device of Example 4 is further characterized in that the plurality of fluid channels include at least two fluid channels.

[0009] In the sixth example ("Example 6"), the device of Example 1 is characterized in that the inlet portion volume and the diffuser portion volume together constitute 10% to 75% of the fluid flow path volume.

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

[0011] In the eighth example ("Example 8"), the device of Example 7 further includes the fact that the ATER is defined by the ratio of the second mean fluid velocity to the first mean fluid velocity divided by the diffuser portion volume.

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

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

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

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

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

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

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

[0019] In the sixteenth example ("Example 16"), the fluid system includes a gas separation device having a housing that defines a fluid passage between an outer surface and an inner surface, the housing having an inlet communicating with the fluid passage and an outlet communicating with the fluid passage, the housing being operable to allow forward and reverse fluid flow from the inlet to the outlet, and the fluid passage defining the fluid passage volume. The system further includes a fluid source coupled to the inlet of the gas separation device and at least one chromatography device having an inlet coupled to the outlet of the gas separation device, the fluid source being 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, and the gas separation device being configured to deliver 0.001 mL of fluid during the forward flow through the housing. -1 ~0.51mL -1 It is configured to show the effective air capture ratio (ATER).

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

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

[0022] In the nineteenth example (Example 19), in the system of Example 16, the gas separation device is configured to exhibit a transition volume of 5 times or less the value of the fluid flow path volume of the gas separation device during the forward flow through the housing.

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

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

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

[0026] In the twenty-third example ("Example 23"), a method for capturing and releasing a certain volume of bubbles within a gas separation device is provided, wherein the gas separation device has a housing that defines a fluid channel having an outer and inner surface, the housing having an inlet and an outlet that are in fluid communication with the fluid channel, and the method includes delivering a fluid in the forward direction through the channel so that the fluid flows from the inlet to the outlet through the gas separation device. The method further includes capturing the volume of gas within the gas separation device, wherein at least a portion of at least one of the inner and outer surfaces of the housing is translucent so that the volume of gas can be observed, and stopping the delivery of the fluid through the fluid channel. The method further includes removing at least a portion of the volume of bubbles from the gas separation device by delivering the fluid in the reverse direction through the fluid channel so that the fluid flows from the outlet to the inlet.

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

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

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

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

[0031] In Example 28, the method of Example 23 is such that the gas separation device has a forward flow through the housing of 0.001 mL -1 ~0.51mL -1 This further includes points indicating the effective air capture ratio (ATER).

[0032] In the twenty-ninth example ("Example 29"), the method of Example 23 further includes the point that the gas separation device exhibits a transition volume of no more than five times the value of the fluid flow path volume during the forward flow through the housing.

[0033] In the 30th example ("Example 30"), the method of Example 24 further includes the fact that the volume of bubbles is between 1% and 100% of the fluid channel volume.

[0034] In the 31st example ("Example 31"), the method of Example 23 further includes the fact that the outlet of the gas separation device is fluid-coupled to the inlet of a chromatography device, thereby arranging 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 the 32nd example ("Example 32"), the gas separation device includes an outer housing, an inlet coupled to the outer housing, an inner component located within the outer housing and defining a diffuser surface and a core, wherein the diffuser surface includes a collector located below the inner component, having a generally dome-shaped longitudinal profile, and a plurality of outlets fluid-coupled to the collector. The gas separation device includes a fluid flow path defined by the inlet, the space between the inner component and the outer housing, the collector, and the plurality of outlets, and a portion of the outer housing, aligned laterally with the diffuser surface and located vertically above the diffuser surface, is translucent or transparent.

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

[0037] In the 34th example ("Example 34"), the device of Example 32 further includes the point that at least a portion of the core has a rectangular cross-section. [Brief explanation of the drawing]

[0038] Brief explanation of the drawing The accompanying drawings are included to provide a further understanding of this disclosure, are incorporated herein, constitute part thereof, illustrate embodiments, and help illustrate the principles of this disclosure together with the description.

[0039] [Figure 1] Figure 1 is a flowchart of a chromatography system according to several embodiments.

[0040] [Figure 2] Figure 2 shows chromatography columns used with gas separation devices according to several embodiments.

[0041] [Figure 3]Figure 3 shows side views of multiple chromatography columns used with gas separation devices according to several embodiments.

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

[0043] [Figure 4] Figure 4 is an enlarged view of the gas separation device shown in Figure 2, according to several embodiments.

[0044] [Figure 5] Figure 5 is an exploded view of the gas separation device shown in Figure 4, according to several embodiments.

[0045] [Figure 6] Figure 6 is a cross-sectional view of the gas separation device shown in Figure 4, according to several embodiments.

[0046] [Figure 7] Figure 7 shows cross-sectional views of the flow profiles of the gas separation device shown in Figure 4, according to several embodiments.

[0047] [Figure 8] Figures 8A to 8F show schematic diagrams of gas separation devices in which bubbles are delivered through the gas separation device according to several embodiments.

[0048] [Figure 9] Figures 9A to 9F show schematic diagrams of gas separation devices in which bubbles are delivered through the gas separation device according to several embodiments.

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

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

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

[0052] [Figure 13] Figure 13 shows the expected transition curves at the outlet of the gas separation device after introducing the salt solution shown in Figure 12, according to several embodiments.

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

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

[0055] [Figure 16] Figure 16 shows transition chromatograms related to the data in Table 2 of Example 2, according to several embodiments. [Modes for carrying out the invention]

[0056] Detailed explanation Those skilled in the art will readily understand that various aspects of this disclosure can be realized by any number of methods and apparatus 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 this disclosure; in this respect, the figures should not be construed as limiting. The term “above” as used herein is understood to mean that an element, such as a polymer film, is directly above another element, or that intervening elements may exist.

[0057] Figure 1 shows a flow diagram of a liquid chromatography system 8 according to several embodiments. The liquid chromatography system 8 may be an affinity chromatography system for separating molecules from a liquid. However, the gas removal concept described herein can utilize a variety of other types of chromatography and related systems, including, but is not limited to, column chromatography, ion exchange chromatography, diligand chromatography, adsorption column chromatography, and gas chromatography. As shown in the figure, 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 collection unit 18, a waste flow 20, a data acquisition device 22, a gas separation device 24, and at least one chromatography device 26.

[0058] As shown in the figure, the fluid source 10 is configured to deliver a fluid mixture to a first injector 12a and subsequently to a 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. Furthermore, in some embodiments, a second injector 12b is configured to inject analytes and / or other molecules into the fluid mixture after the fluid mixture has been 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 may include only one of the first injector 12a and the second injector 12b.

[0059] Furthermore, the pump 14 is configured to pressurize the liquid chromatography system 8 and help deliver 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 may include one pump 14, while in other embodiments, the liquid chromatography system 8 includes two or more pumps. As shown in the figure, the gas separation device 24 is fluidically coupled with the second injector 12b and the chromatography device 26. During the operation of the liquid chromatography system 8, the fluid mixture is delivered through the gas separation device 24 to the chromatography device 26 or the waste flow 20. As will be further described below, the gas separation device 24 helps remove unwanted gases from the fluid mixture flow passing through the liquid chromatography system 8. The chromatography device 26 separates the target analyte or molecules from the fluid mixture.

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

[0061] Figure 2 shows an example of a chromatography apparatus 27 that can be used in combination with the chromatography device 26 of the liquid chromatography system 8. As shown, the housing 28 encloses the chromatography device 26 (not shown), which has an inlet portion 30 and an outlet portion 32 extending from the housing 28. The inlet portion 30 is located on the opposite side of the outlet portion 32. The chromatography device, for example, the chromatography device 26, can define or contain a total volume. The total volume is defined by the volume between the inlet portion 30 and the outlet tube 34 of the chromatography device, for example, the chromatography device 26 (not shown) (also called the internal volume or fluid volume). More specifically, this volume includes both the functional bed volume of the chromatography device, which is defined as the volume that can contain or maintain fluid during the 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 take on various other configurations based on the desired function and target process used. In some embodiments, the chromatography device 26 is similar to the chromatography device described by Clinger et al. in PCT / US21 / 049969, titled "Affinity chromatography device including a fibrillated polymer membrane and manifold including the same." In any case, the chromatography device 26 may include an inlet tube in the inlet portion 30. An outlet tube 34 may extend from the outlet portion 32 and be fluid-connected thereto. Although the liquid chromatography system 8 and Figure 2 are shown as including only one chromatography device 26, in some embodiments, multiple chromatography devices, e.g., chromatography devices 26, can be incorporated. For example, two or more chromatography devices, each having similar or different configurations, can be incorporated as needed. The chromatography devices, including the chromatography device 26, are coupled to each other at the inlet by a distributor or manifold, which can then be coupled to a gas separation device 24. In other words, the gas separation device 24 can serve one or more chromatography devices. Therefore, although we refer to it here as a single chromatography device such as chromatography device 26, in some embodiments this can refer to multiple chromatography devices such as chromatography devices 26 coupled to each other at the inlet.

[0063] Figure 3A shows such a variation of the chromatography device 26, which includes at least four chromatography devices within a housing 28 and is fluidly coupled to the 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 can thus be arranged in parallel. The ability to use at least two manifolds in parallel has the advantage of increasing the volumetric capacity while using the chromatography devices described herein. In other words, the configuration having multiple chromatography devices 26a-d eliminates the need to move to larger volume chromatography devices. Furthermore, arranging the manifolds in parallel as shown in Figure 3A reduces concerns about overpressurizing the chromatography device 26. In further embodiments, the liquid chromatography system 8 can incorporate four or more chromatography devices.

[0064] Furthermore, in some embodiments, the liquid chromatography system 8 can incorporate one or more chromatography devices 26 in combination with one or more gas separation devices 24. For example, Figure 3B shows a further embodiment of some of the liquid chromatography systems 8 (Figure 1), in which the chromatography devices 26 include a first chromatography device 26a and a second chronography device 26b arranged in parallel. Each of the first chromatography device and the second chromatography devices 26a, 26b is coupled to a gas separation device. Exemplarily, the first chromatography device 26a is fluid-coupled to a first gas separation device 24a, and the second chromatography device 26b is fluid-coupled to a second gas separation device 24b. Furthermore, 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 connected to the first manifold 6a, thereby delivering fluid from the fluid source 10 (Figure 1) through the manifold 6a to the gas separation devices 24a, 24b and the chromatography devices 26a, 26b in parallel. Similarly, the outlet portion 32a of the first chromatography device 26a and the outlet portion 32b of the second chromatography device 26b are fluidically connected to the second manifold 6b, thereby converging the fluid after being delivered through the chromatography devices 26a, 26b into a single fluid flow path. Although two gas separation devices are illustrated, any number of gas separation devices can be incorporated. For example, the liquid chromatography system 8 may include three or more gas separation devices and three or more chromatography devices for attachment to the gas separation devices.

[0065] Figure 4 shows an enlarged view of a gas separation device 24 coupled to the inlet portion 30 of a chromatography device (not shown) within 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 Figures 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 (Figure 4). After passing through at least one outlet 44, the fluid can be delivered to a chromatography device 26. More specifically, at least one outlet 44 is coupled to the inlet portion 30 of the chromatography device 26, thereby coupling the gas separation device 24 and the chromatography device 26 in series with each other. More specifically, at least one outlet 44 may be fluid-coupled to a channel and / or tube that fluid-couples to the inlet tube (not shown) of the chromatography device 26. In some embodiments, at least one outlet 44 may be fluid-coupled to a channel that fluid-couples to a manifold, such as a manifold 6A (Figure 3A), to distribute the fluid to multiple chromatography devices 26. Furthermore, in other embodiments, at least one outlet 44 may be directly coupled to the fitting and the inlet tube of the chromatography device 26. The passage of fluid through the gas separation device 24 will be further described herein with reference to Figures 5 and 6.

[0066] Figure 5 shows an exploded view of the gas separation device 24. As shown, the gas separation device 24 includes an inlet tube 40 coupled to an upper 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 used when assembling the gas separation device 24. The inlet tube 40 includes an opening 36 extending to a central portion 38. The central portion 38 is coupled to the upper portion 42, which can 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, a variety of other configurations can be implemented, and they are all considered to be within the scope of this disclosure. Furthermore, the upper portion 42 may be defined as circular or disk-shaped, as shown in the exemplary embodiment of Figure 5, but a variety of other configurations may be implemented. For example, in some embodiments, the inlet tube 40 and / or the upper portion 42 may have rectangular, triangular, or other applicable configurations. Furthermore, the inlet tube 40 and the upper portion 42 may be made of a transparent or translucent material. For example, the inlet tube 40 and / or the upper portion 42 may be made of a transparent or translucent polymer such as a cyclic olefin copolymer (COC) or an acrylic polymer. However, a variety of other applicable transparent or translucent materials may be used to form the inlet tube 40 and / or the upper portion 42. Transparent may be defined herein as a material through which light can pass directly. Translucent may be defined herein as a material through which only a portion of the light directed at it can pass. In some embodiments, the inlet tube 40 may not be transparent or translucent, while the upper portion 42 is either transparent or translucent. In other embodiments, only a portion of the upper portion 42 is transparent or translucent. Whether transparent or translucent, as further described herein, the material of the inlet tube 40 and / or the upper portion 42 may be selected so that bubbles located vertically below the upper 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] The internal component 60 will be further described with reference to Figure 5. The internal component 60 includes a top surface 62, also referred to herein as the diffuser surface, and a core 64 extending below the top surface 62. As best shown in the cross-sectional view of Figure 6, the top surface 62 may include a longitudinal profile having a generally domed profile that extends along the longitudinal axis L. A generally domed profile can be defined herein as the top surface 62 having a domed or curved shape, with the maximum vertical height of the top surface 62 generally located within the longitudinal center of the top surface 62, and the vertical height of the top surface 62 decreasing as the top surface 62 extends outward from the longitudinal center. In other embodiments, the top surface 62 may have a generally flat / planar longitudinal profile, for example, as shown in the modified gas separation device 924 in Figure 14H. In other words, the top surface 62 may have a substantially constant vertical height across its width and longitudinal range. Furthermore, various other longitudinal profiles can be incorporated, for example, frustoconical and / or conical longitudinal profiles can be implemented. However, regardless of the profile of the top surface 62, as shown in Figures 5 and 6, the top surface 62 of the inner component 60 extends to a vertical height lower than the lowest vertical height of the central portion 38 of the inlet tube 40. This is beneficial in that when the fluid can be delivered in the reverse direction through the gas separation device 24, the fluid will not be confined above the top surface 62 and near the inlet tube 40, but will instead flow out of the inlet tube 40. Furthermore, the core 64 can generally define an annular cross-sectional shape. However, various other configurations can be implemented. For example, the core 64 can 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 can be incorporated into the gas separation device. Furthermore, 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 different from the first cross-sectional shape. In a further embodiment, the core 64 may include three or more cross-sectional shapes.

[0068] The outer housing 50 of the gas separation device 24 will be further described with reference to Figure 5. The outer housing 50 includes a base 52, a cavity 54 extending within the base 52 and in contact with the outer wall 56, and at least one outlet 44 extending from the bottom of the base 52. Exemplarily, the outer wall 56 includes a plurality of grooves 59 extending circumferentially within 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 made of a polymer material such as polypropylene, polyetheretherketone (PEEK), cyclic olefin copolymer, polycarbonate, or any other suitable polymer material. In other embodiments, the outer housing 50 may be made of a metallic material or any other applicable material. The base 52 generally has a circular cross-section, but the base 52 can be fitted with a variety of other shapes. Furthermore, as shown, the plurality of seals 66 include a first seal 66a and a second seal 66b housed in the grooves 59 of the outer wall 56. In some embodiments, the multiple seals 66 are O-ring seals, but various other types of seals can be implemented. Furthermore, although the connector ring 68 is generally shown as having a C-shape, various other configurations and / or shapes of the connector ring 68 can be incorporated, and these are considered to be within the scope of this disclosure.

[0069] The assembled gas separation device 24 will be further described herein with reference to the cross-sectional view in Figure 6. As shown, the inlet tube 40 is shown with its upper portion 42 coupled to the base 52 of the outer housing 50. More specifically, the upper portion 42 is coupled to a groove 59 in the wall 56 of the outer housing 50. As shown, the generally dome-shaped profile of the upper portion 42 matches the generally dome-shaped profile of the upper surface 62 of the inner component 60, forming a widened gap between the upper portion 42 and the upper surface 62. A connector ring 68 engages with the base 52 and is positioned above the upper portion 42, ensuring that the upper portion 42 is securely positioned within the base 52. Multiple seals 66, exemplary O-ring seals, are used during the assembly of the gas separation device 24 to ensure fluid sealing within the gas separation device 24. Specifically, the seals 66 can contribute to fluid sealing between the inner component 60, the upper surface 62, and the base 52. Furthermore, the inner component 60 is positioned within the cavity 54 such that its central axis C aligns 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, creating a concentric gap between the inner component 60 and the outer wall 56 of the base 52. Thus, the core 64 of the inner component 60 can be defined in an annular shape. In other words, the inner component 60 is centrally positioned within the outer housing 50. However, in other embodiments, the central axis C of the inner component 60 may be laterally offset from the central axis D of the inlet tube 40. In this way, fluid can flow through the gap between the inner component and the inner surface of the outer housing 50.

[0070] Below the inner component 60, the base 52 includes a collector 58 defined as a region for joining the gap extending between the inner component 60 and the outer wall 56 of the base 52. Furthermore, at least one outlet 44, exemplary first and second outlets 44a, 44b, extend from the collector 58, which extend outward and can be coupled to the inlet portion of the chromatography device 26 (Figure 3A). Although shown as two outlets 44a, 44b, at least one outlet 44 may include one, two, three, four or more outlets. As further described with reference to Figures 6 and 7, the gap between the top surface 62 and the upper portion 42 within the inlet tube 40 and the gap 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, referring to the cross-sectional views of the fluid flow profile of the device 24 in Figures 6 and 7, the fluid channel 70 is formed to extend through the gas separation device 24. The fluid channel 70 includes an inlet portion 72, a diffuser portion 74, a recombination portion 76, and an outlet portion 78. As shown, the fluid channel 70 extends downward from the opening 36 of the inlet tube 40 through the central portion 38 of the inlet tube 40, and into the space between the top surface 62 and the upper portion 42. Thus, the inlet tube 40 defines the inlet portion 72 of the fluid channel 70 that extends through the inlet tube 40. As the fluid flows through the inlet portion 72 of the fluid channel 70, the fluid defines a first average velocity μ1.

[0072] The fluid channel 70 extends through the inlet portion 72 and then extends within 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. In this way, the fluid channel 70 defines a diffuser portion 74 that extends vertically between the top surface 62 and the upper portion 42 and laterally within the outer housing 50. Within the diffuser portion 74, the velocity of the fluid passing through the fluid channel 70 decreases as the fluid flow collides with the top surface 62 and changes direction, and is defined by a second mean velocity μ2.

[0073] Furthermore, as illustrated, the fluid channel 70 can extend downward through the gap 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 way, the fluid delivered through the fluid channel 70 is distributed into multiple fluid channels and extends downward to the collector 58. Thus, the fluid channel 70 can define a recombination portion 76 extending 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 gap extending around the inner component 60. In other embodiments, the recombination portion 76 can be defined by a plurality of separate channels extending around the core 64 of the inner component 60.

[0074] The concentric configuration of the inner component 60 and the base 52 of the outer housing 50 ensures that any fluid passages through which fluid may pass around the inner component 60 are at the same distance from the top surface 62 and the collector 58. This ensures that the fluid flow maintains a plug flow through the fluid passage 70 and that fluid molecules that were pre-grouped before contacting the top surface 62 are recombined at the collector 58. In other words, the configuration of the inner component 60 allows for a fluid flow that reduces the amount of mixing within and / or between fluids.

[0075] As shown in the figure, once the fluid passes through the collector 58, it can extend to at least one outlet 44 and exit the gas separation device 24. Thus, the fluid passage 70 defines an outlet portion 78 that extends perpendicularly between the bottom of the collector 58 and the outside of the gas separation device 24.

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

[0077] As will be further described with reference to the Test Method and Examples, the gas separation device 24 is configured such that, if there is a volume of bubbles contained in the fluid delivered in the forward direction through the fluid channel 70, the volume of bubbles is trapped within the diffuser section 74 and between the top surface 62 and the upper section 42 as the fluid passes through the diffuser section 74. The forward direction is defined as the direction in which the fluid extends from the inlet section 72 to the outlet section 78. As the fluid flows through the fluid channel 70 in this direction, the volume of bubbles continues to be trapped within the diffuser section 74. The 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, the operator can interact with a user interface used to send commands to components of the liquid chromatography system 8 (Figure 1) and 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 so that the fluid is delivered through the gas separation device 24 from the outlet section 78 to the inlet section 72. The reverse flow through the fluid channel 70 causes at least a portion of the bubble volume to exit through the inlet tube 40 of the gas separation device 24. In this way, the reverse flow of the fluid causes at least a portion of the volume of bubbles trapped in the diffuser section 74 to exit through the inlet tube 40 along with the fluid. In this operating state, the fluid is delivered from the gas separation device 24 to the waste flow 20, ensuring that the bubbles exit the liquid chromatography system 8 and are not reintroduced into the gas separation device 24.

[0078] Since at least the upper portion 42 is transparent or translucent, the operator can visualize the volume of bubbles trapped in the diffuser portion 74 and visualize the removal of bubble volume from the diffuser portion 74. In this way, the operator can monitor the gas separation device 24 and stop the flow and reverse it once a desired volume of bubbles trapped in the gas separation device 24 is visualized. For example, in some embodiments, the operator can monitor the gas separation device 24 and stop the flow when the bubble volume reaches the maximum bubble volume (which may be defined as at least 95% of the volume of the diffuser portion 74). Furthermore, the fluid can be delivered in reverse for various amounts of time controlled by the operator. For example, the fluid flow may 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 bubbles is removed from the diffuser portion 74.

[0079] The operator can then stop the fluid flow and then operate the system to allow the fluid to flow again in the forward direction. When this happens, the inlet tube 40 is reconnected to a fluid source, for example, fluid source 10 (Figure 1), and the outlet 44 is connected to the 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 described above, the gas separation device 24 offers the advantage of efficiently capturing bubbles within the gas separation device 24 and easily reversing the fluid flow to remove the captured bubbles from within the gas separation device 24. As will be further described with reference to the test methods and examples, the bubble capture capability of the gas separation device 24 can be quantified by the effective air capture ratio (ATER). The ATER is calculated by dividing the ratio of the second mean velocity μ2 to the first mean velocity μ1 by the diffuser portion volume. The gas separation device 24 is characterized by an ATER of approximately 0.001 mL while the fluid flows forward through the gas separation device 24. -1 ~about 0.51mL -1The device is configured to be within the specified range. When the ATER is maintained within the above range, the gas separation device 24 can capture bubbles from the fluid passing through the fluid channel 70, trap the bubbles in the diffuser section 74, and release the bubbles when the fluid flows back through the fluid channel 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 introduced 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 will be further described with reference to the test methods and examples, the gas separation device 24 can exhibit a transition volume of about five 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 five times or less the value of the fluid flow path volume. Furthermore, when calculated based on the transition volume of the flow passing through both the gas separation device 24 and the chromatography device 26, the transition volume can be five 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 the gas separation device 24 can be about 1% to 50% of the total volume of the chromatography device 26. However, various other ratios of the fluid flow volume of the gas separation device 24 to the chromatography device 26 may be implemented.

[0082] Those skilled in the art will readily understand that various aspects of this disclosure can be realized by any number of methods and apparatus 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 this disclosure; in this respect, the figures should not be interpreted as limiting.

[0083] Test method How to simulate liquid flow through a device A computational fluid dynamics (CFD) model was developed using 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 described and discussed here. By solving the governing equations, the fluid velocity in three directions, fluid pressure, salt concentration, and turbulence parameters are calculated for each cell. As previously mentioned, Figure 6 shows a cross-sectional view of the gas separation device 24 including the fluid flow path modeled by computational fluid dynamics (CFD), while Figure 7 shows a cross-sectional view of the gas separation device 24 including the schematic fluid domain of the gas separation device 24. Since the test method described 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-meaned Navier-Stokes equations, which include the conservation of mass and momentum. Turbulence in the fluid flow through the fluid channel was predicted using the shear stress transport k-omega model.

[0085] The equations for conservation of mass and momentum are given as follows:

number

number

[0086] A constant mass flow rate was defined at the inlet portion 72 of the gas separation device 24 (Figs. 6 - 7). The outlet was fixed at zero gauge pressure. For the liquid, an incompressible assumption was made, and for air, an ideal gas was assumed. The properties used in this method include the properties of water and air in the liquid phase and gas phase, respectively. The density of the liquid was 997.561 kg / m 3 , and the viscosity was set to be 8.8871 Pa·s. The interfacial surface force was modeled as a body force using the continuum surface force (CSF) approach of Brackbill et al. (Brackbill, J. U., Kothe, D. B., and Zemach, C. 1992. A continuum method for modeling surface tension, J. Comp. Physics, 100, pp. 335 - 354). The surface tension constant between the liquid and gas was fixed at 0.072 N / m. However, various other surface tension and density values can be used to model the required fluid and material properties.

[0087] A method for simulating the behavior of bubbles passing through the device and determining the air capture effectiveness parameter in the simulation The volume of fluid (VOF) multiphase model is used to predict the interface between air and liquid in the gas separation device 24. The distribution of the phases (air and liquid) and the position of the interface are described by the field of the phase volume fraction αi, and the fraction is shown below. Vi is the volume of phase i in the cell, and V is the volume of the cell. [Number]

[0088] The sum of the volume fractions of all phases in the cell must be equal to 1, as shown by the following equation. Here, N is the total number of phases. [Number]

[0089] Fluids present within a cell 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 initial conditions for the bubble simulation. Initially, there is only water passing through the gas separation device 24 at a fixed flow rate. Next, a fixed volume of bubbles is injected at the inlet portion 72 of the gas separation device 24.

[0091] The bubbles are trapped by volumetric expansion within the simulated gas separation device 24. Such expansion affects the fluid flow properties, including 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] In the above equation, u2 is the average fluid velocity in the diffuser portion 74, u1 is the average fluid velocity in the inlet portion 72, and V is the volume of the diffuser portion 74.

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

[0095] For example, Figures 8A to 8F show that ATER is approximately 0.938 mL over the simulated time state. -1Figures 8A to 8F show a simulated gas separation device 24 or a slight variation thereof. As shown in Figures 8A to 8F, the fluid flows through the fluid channel 70 of the gas separation device 24, and the bubble 80 is delivered into the system, but the bubble 80 moves throughout the gas separation device 24 and is not trapped in the diffuser portion 74 of the gas separation device 24. Specifically, Figure 8A shows the simulation at a simulation time point of approximately 0.1 seconds after the bubble 80 is delivered into the inlet portion 72. Figure 8B shows the simulation inside the gas separation device 24 at a time point of approximately 0.2 seconds after the bubble 80 is delivered into the inlet portion 72. As shown in Figures 8A to 8F, the bubble 80 is located within the diffuser portion 74. Furthermore, Figure 8C shows the simulation at a time point of approximately 0.3 seconds after the bubble 80 is delivered. As shown, the bubble has passed through the diffuser portion 74 and moved to the recombination portion 76. Figures 8D and 8E show the bubbles 80 placed within the diffuser section 74, recombination section 76, and outlet section 78 of the gas separation device 24. Figure 8F shows the system approximately 0.1 seconds after the bubbles 80 are delivered to the inlet section 72, at which point the bubbles 80 have passed through the entire gas separation device 24. Thus, Figures 8A to 8F show how the bubbles 80 pass through the entire gas separation device 24 rather than being trapped within the diffuser section 74.

[0096] Figures 9A-9F show the simulation method for the gas separation device 24, where ATER is approximately 0.116 mL. -1This has been simulated. As shown in the figure, the bubbles 80 are delivered to the gas separation device 24 along with the fluid and are trapped within the diffuser section 74. Specifically, Figure 9B shows the fluid and bubbles 80 extending within the diffuser section 74. As the fluid continuously passes through the gas separation device 24, Figures 9C to 9F show that the bubbles 80 remain trapped within the diffuser section 74 and do not extend downward within the gas separation device 24. This is desirable for the gas separation device 24 to function properly so that the bubbles 80 are not delivered into the chromatography device 26 (Figure 2).

[0097] How to simulate the flow transition of a salt solution through a device. Salt was introduced into the flow field as a tracer, and its movement 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 These are the salt concentration in the fluid, the fluid velocity, and the diffusivity of the salt, respectively. In the above model formulation, it is assumed that the fluid properties do not change due to the salt. The salt is introduced as a step function at the inlet boundary.

[0099] Figures 10A–10F show CFD models of the gas separation device 24 as the salt solution is being inserted through the fluid channel 70. Specifically, Figure 10A shows the gas separation device 24 before the salt solution is inserted. Figure 10B shows the CFD model of the gas separation device 24 when the salt solution is inserted into the inlet portion 72 of the gas separation device 24. Furthermore, Figures 10C–10D show the salt solution being further inserted through the fluid channel 70 of the gas separation device 24, and also show the mixing of the fluids. As shown in Figures 10E and 10F, as the insertion of the salt solution continues over time, the mixing decreases and the fluid channel 70 is completely consumed by the salt solution.

[0100] This method can be applied to several different device designs by changing the parameters incorporated into the model. Furthermore, the model allows for the determination of transition curves, as shown in Figure 11.

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

[0102] A method for determining the volume required to complete a simulated salt solution flow transition through a device. While increasing the fluid flow volume of a gas separation device can reduce the ATER, it also increases the transition volume of the gas separation device. A high transition volume is undesirable for chromatography applications. Increasing the transition volume of a device can increase solution consumption and reduce process efficiency. To actually measure the transition volume of a gas separation device, a transition test is typically performed. A transition experiment involves pushing a fluid out of a gas separation device by introducing a new fluid. Therefore, 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 conductivity of the salt solution and water were set to 21.5 and 0.01 mS / cm, respectively. The transition volume was measured when the conductivity at the outlet reached 21 mS / cm, and this was determined to be the steady-state conductivity.

[0103] Experimental method for confirming air trapping effectiveness Gas separation device 24 was physically constructed from design 1 in Table 1 and is referred to here as gas separation device A. Gas separation device A, mounted on top of a helical manifold affinity chromatography device as described in PCT application number PCT / US21 / 049969 by Clinger et al., was installed on an AKTA Pilot liquid chromatography system (Cytiva, Marlborough, Massachusetts), and phosphate-buffered saline (PBS) was pumped to gas separation device A and the helical manifold affinity chromatography device at a flow rate of 696 mL / min. Bubbles were introduced into gas separation device A by removing the feed tube from the PBS buffer, and the feed tube was returned to the PBS buffer approximately 1 second after removal. A few seconds after the bubbles were trapped in gas separation device A, the pump of the liquid chromatography system was reversed to discharge the bubbles, along with a small amount of PBS, into the waste stream.

[0104] Experimental methods for confirming transition volume The affinity chromatography device 26 described by Clinger et al., PCT application number PCT / US21 / 049969, was installed in an AKTA Pilot liquid chromatography system (Cytiva, Marlborough, Massachusetts) with or without gas separation device A attached to the inlet of the affinity chromatography device. Phosphate-buffered saline (PBS) was introduced into 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 until a conductivity of 0.15 mS / cm was reached at the outlet of the device, with or without gas separation device A attached to the inlet of the affinity chromatography device. This conductivity represents a complete volume transition from PBS to water. The column volume is defined as the total volume of chromatography device 26 (Figure 2). [Examples]

[0105] example Example 1: Results of a simulation using computational fluid dynamics (CFD) A total of 24 unique modified designs were generated for the gas separation device 24 (Figure 3), and their flow performance was simulated using the aforementioned test method. Figures 14A to 14X show cross-sectional views of the simulated designs 1 to 24, respectively. Specifically, Figure 14A shows a cross-sectional view of gas separation device 24. Figure 14B shows a modified gas separation device 324 having a fluid channel 370 with a linear recombination section 376, and no indentation within the recombination section 376. Figure 14C shows a modified gas separation device 424 defining a fluid channel 470 with a uniform diffuser section 474 and a linear recombination section 476. Furthermore, Figure 14D shows a modified gas separation device 524 having a modified fluid channel 570 with a thinner diffuser section 574 such that the volume of the diffuser section 574 is smaller than the volume of the diffuser section 74 (Figure 14A). Furthermore, Figure 14E shows a modified gas separation device 624 having a modified fluid channel 670 that extends linearly downward and has a reconnecting portion 674 that follows a laterally extending portion. Furthermore, Figure 14F shows a modified gas separation device 724 having a modified fluid channel 770 that has a reconnecting portion 776 that extends linearly and laterally from a corner that connects with the diffuser portion 774 of the gas separation device 724.

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

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

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

[0109] Air bubble delivery was simulated using each of the above models. The simulation results are shown in Table 1. The result showed an effective air capture ratio (ATER) of 0.51 mL. -1 When the value exceeded a certain threshold, it indicated that the bubbles had passed through the respective gas separation device. [Table 1]

[0110] Example 2: Experimental confirmation of air trapping effectiveness and transition volume The series of time-lapse diagrams taken from still photographs shown in Figures 15A-15C demonstrate that the bubbles introduced into the gas separation device A are visualized and removed using the appropriate test method described above. As shown in Figure 15A, before the insertion of the bubbles, the fluid flows through the gas separation device A, and no bubbles are shown being trapped in the diffuser section 74. However, during the insertion of bubbles 80, bubbles 80 are shown within the diffuser section 74 (see Figure 15B) and can be observed from outside the gas separation device A. Furthermore, after the fluid flow through the gas separation device A reverses, as shown in Figure 15C, the bubbles are no longer seen within the diffuser section 74 and are discharged from the gas separation device A.

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

[0112] Those skilled in the art will readily understand that various aspects of this disclosure can be realized by any number of methods and apparatus configured to perform the intended functions. It should also be noted that the examples and methods herein should not be construed as limiting. (Aspect) (Aspect 1) A gas separation device comprising a housing that defines a fluid passage between an outer surface and an inner surface, wherein the housing has an inlet communicating with the fluid passage and an outlet communicating with the fluid passage, the housing is operable to allow fluid flow in the forward direction from the inlet to the outlet and in the reverse direction from the outlet to the inlet, and the fluid passage defines the fluid passage volume. An inlet portion is positioned to receive fluid from the inlet during the forward fluid flow through the housing, A diffuser portion is positioned to receive fluid from the inlet portion during the forward fluid flow through the housing. A recombination section is positioned to receive fluid from the diffuser section during the forward fluid flow through the housing. An outlet portion is positioned to receive fluid from the recombination portion during the forward fluid flow through the gas separation device, wherein the outlet portion defines the outlet portion volume. Includes, The aforementioned inlet portion defines the volume of the inlet portion, The aforementioned diffuser portion defines the volume of the diffuser portion, The aforementioned recombination portion defines the volume of the recombination portion, The gas separation device allows 0.001 mL of fluid to flow through the housing in the forward direction. -1 ~0.51mL -1 A gas separation device configured to exhibit an effective air capture ratio (ATER). (Aspect 2) The gas separation device according to embodiment 1, configured to exhibit a transition volume of five times or less the value of the fluid flow channel volume during the forward fluid flow through the housing. (Aspect 3) The gas separation device according to embodiment 1, further comprising a fluid channel exiting from the outlet. (Aspect 4) The gas separation device according to embodiment 1, further comprising a manifold that is in fluid communication with the outlet, the manifold dividing the fluid coming out of the outlet into a plurality of fluid passages. (Aspect 5) The gas separation device according to embodiment 4, wherein the plurality of fluid channels include at least two fluid channels. (Aspect 6) The gas separation device according to embodiment 1, wherein the volume of the inlet portion and the volume of the diffuser portion together are 10% to 75% of the fluid flow path volume. (Aspect 7) A gas separation device according to embodiment 1, wherein a first mean fluid velocity used to determine the ATER is determined by the velocity of the fluid flowing through the inlet, and a second mean fluid velocity used to determine the ATER is determined by the velocity of the fluid flowing through the diffuser portion. (Pattern 8) The gas separation device according to embodiment 7, wherein ATER is defined by the ratio of the second mean fluid velocity to the first mean fluid velocity divided by the diffuser portion volume. (Aspect 9) The gas separation device according to embodiment 1, wherein at least one of the inner and outer surfaces of the diffuser portion defines a generally dome-shaped longitudinal profile. (Aspect 10) The gas separation device according to embodiment 1, wherein at least one of the inner and outer surfaces of the diffuser portion defines a generally flat longitudinal profile. (Aspect 11) The gas separation device according to embodiment 1, wherein at least one of the inner and outer surfaces of the diffuser portion defines a conical or frustoconical profile. (Aspect 12) The gas separation device according to embodiment 1, wherein at least a portion of the housing is translucent or transparent, so that the gas volume in the diffuser portion can be seen through the housing. (Aspect 13) The gas separation device according to embodiment 1, wherein the recombination portion is defined by a plurality of individual channels extending between the inner and outer surfaces of the fluid flow path. (Aspect 14) The gas separation device according to embodiment 1, wherein the recombination portion is defined by an annular channel extending between the inner and outer surfaces of the fluid flow path. (Aspect 15) The gas separation device according to embodiment 1, wherein the recombination portion is defined by the inner and outer surfaces of a fluid channel having a concentric configuration. (Aspect 16) A gas separation device having a housing that defines a fluid passage between its outer surface and inner surface, wherein the housing has an inlet communicating with the fluid passage and an outlet communicating with the fluid passage, and the housing is operable to allow 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 including an inlet coupled to the outlet of the gas separation device, Includes, The aforementioned fluid channel defines the fluid channel volume, The fluid source is configured to deliver a forward flow through the gas separation device and the chromatography device, and the chromatography device is operable to allow a reverse flow through the chromatography device. The gas separation device, during the forward flow through the housing, contains 0.001 mL -1 ~0.51mL -1 A fluid system configured to exhibit an effective air trapping ratio (ATER). (Aspect 17) The system according to embodiment 16, wherein a first mean fluid velocity used to determine the ATER is defined by the velocity of the fluid flowing through the inlet, a second mean fluid velocity used to determine the ATER is defined by the velocity of the fluid flowing through the diffuser portion, and the ATER is defined by the ratio of the second mean fluid velocity to the first mean fluid velocity divided by the volume of the diffuser portion. (Aspect 18) The system according to embodiment 16, wherein the chromatography device has a total volume defined by the volume between the fluid inlet and the fluid outlet of the chromatography device, and the fluid flow volume of the gas separation device is 50% or less of the total volume of the chromatography device. (Aspect 19) The system according to embodiment 16, wherein the gas separation device is configured to exhibit a transition volume of five times or less the value of the fluid flow channel volume of the gas separation device during forward flow through the housing. (Aspect 20) The system according to embodiment 16, wherein the gas separation device further includes a manifold in fluid communication with at least one outlet, the manifold divides the fluid exiting the outlet into a plurality of fluid passages. (Aspect 21) The system according to embodiment 16, wherein 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, 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, the diffuser portion defining the diffuser portion volume. (Aspect 22) The system according to embodiment 21, wherein at least a portion of one or both of the inner and outer surfaces of the fluid channel defining the diffuser portion is translucent or transparent, so that bubbles can be observed within the diffuser portion. (Aspect 23) A method for capturing and releasing a certain volume of bubbles within a gas separation device, wherein the gas separation device has a housing that defines a fluid passage having an outer surface and an inner surface, and the housing has an inlet that communicates with the fluid passage and an outlet that communicates with the fluid passage, and this method is Delivering the fluid in the forward direction through the flow path such that the fluid flows from the inlet to the outlet through the gas separation device. To capture the aforementioned volume of gas within the aforementioned gas separation device, To stop the delivery of fluid through the aforementioned fluid passage, and To remove at least a portion of the volume of bubbles from the gas separation device by delivering the fluid in the reverse direction through the fluid channel so that the fluid flows from the outlet to the inlet, Includes, A method wherein at least a portion of at least one of the inner and outer surfaces of the housing is translucent so that the volume of gas can be observed. (Aspect 24) The method according to embodiment 23, wherein the fluid flow path includes an inlet portion disposed to receive fluid from the inlet during a forward fluid flow through the housing, a diffuser portion disposed to receive fluid from the inlet portion during a forward flow through the housing, a recombination portion disposed to receive fluid from the diffuser portion during a forward flow through the housing, and an outlet portion disposed to receive fluid from the recombination portion during a forward flow through the gas separation device, the diffuser portion defining the diffuser portion volume. (Aspect 25) The method according to embodiment 24, wherein capturing the aforementioned volume of bubbles includes capturing the aforementioned volume of bubbles within the diffuser portion of the gas separation device. (Aspect 26) The method according to embodiment 23, wherein when the volume of the bubbles approaches the maximum bubble volume defined by approximately 95% of the diffuser portion volume, the flow is reversed. (Aspect 27) The method according to embodiment 23, further comprising delivering fluid through the fluid channel in the forward direction from the inlet to the outlet of the housing after a portion of the aforementioned volume of bubbles has exited the gas separation device. (Aspect 28) The gas separation device, during the forward flow through the housing, contains 0.001 mL -1 ~0.51mL -1 The method according to embodiment 23, which shows the effective air capture ratio (ATER). (Aspect 29) The method according to embodiment 23, wherein the gas separation device exhibits a transition volume of five times or less the value of the fluid flow path volume during the forward flow through the housing. (Aspect 30) The method according to embodiment 24, wherein the volume of bubbles is 1% to 100% of the fluid channel volume. (Aspect 31) The method according to embodiment 23, wherein the outlet of the gas separation device is fluid-coupled to the inlet of a chromatography device, thereby arranging the gas separation device and the chromatography device in series, and the method further comprises delivering a fluid through the outlet of the gas separation device to the inlet of the chromatography device. (Aspect 32) Outer housing, The inlet connected to the outer housing, An inner component disposed within the outer housing that defines the diffuser surface and core, A collector and, located below the aforementioned internal component. Multiple outlets fluidly coupled to the collector, The fluid flow path defined by the inlet, the distance between the inner component and the outer housing, the collector and the plurality of outlets, A gas separation device including, The diffuser surface generally has a dome-shaped longitudinal profile. A gas separation device in which a portion of the outer housing, which is aligned laterally with the diffuser surface and positioned vertically above the diffuser surface, is translucent or transparent. (Aspect 33) The gas separation device according to embodiment 32, wherein at least a portion of the core has an annular cross-section. (Aspect 34) The gas separation device according to embodiment 32, wherein at least a portion of the core has a rectangular cross-section.

Claims

1. A gas separation device comprising a housing defining a fluid passage between an outer surface and an inner surface, wherein the housing has an inlet and an outlet extending from a first end and a second end, respectively, the first end being opposite to the second end, the inlet and the outlet being in fluid communication with the fluid passage, thereby enabling the gas separation device to be operated by a pump located outside the gas separation device to allow fluid flow in the forward direction from the inlet to the outlet and in the reverse direction from the outlet to the inlet, the fluid passage defining the fluid passage volume, An inlet portion is positioned to receive fluid from the inlet during the forward fluid flow through the housing, A diffuser portion is positioned to receive fluid from the inlet portion during the forward fluid flow through the housing. A recombination section is positioned to receive fluid from the diffuser section during the forward fluid flow through the housing. An outlet portion is positioned to receive fluid from the recombination portion during the forward fluid flow through the gas separation device, wherein the outlet portion defines the outlet portion volume. Includes, The aforementioned inlet portion defines the volume of the inlet portion, The aforementioned diffuser portion defines the volume of the diffuser portion, The aforementioned recombination portion defines the volume of the recombination portion, The gas separation device allows 0.001 mL of fluid to flow through the housing in the forward direction. －１ ~0.51 mL －１ It is configured to exhibit an effective air capture ratio (ATER), The ATER is a gas separation device calculated by dividing the ratio of the second mean fluid velocity μ2 to the first mean fluid velocity μ1 by the diffuser portion volume.

2. The gas separation device according to claim 1, wherein the device is configured to exhibit a transition volume of five times or less the value of the fluid flow path volume during the forward fluid flow through the housing.

3. The gas separation device according to claim 1, further comprising a fluid channel exiting from the outlet.

4. The gas separation device according to claim 1, further comprising a manifold in fluid communication with the outlet, wherein the manifold divides the fluid exiting the outlet into a plurality of fluid passages.

5. The gas separation device according to claim 4, wherein the plurality of fluid channels include at least two fluid channels.

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

7. The gas separation device according to claim 1, wherein the first mean fluid velocity μ1 used to determine ATER is defined by the velocity of the fluid flowing through the inlet, and the second mean fluid velocity μ2 used to determine ATER is defined by the velocity of the fluid flowing through the diffuser portion.

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

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

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

11. The gas separation device according to claim 1, wherein at least a portion of the housing is translucent or transparent, so that the gas volume in the diffuser portion can be seen through the housing.

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

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

14. The gas separation device according to claim 1, wherein the recombination portion is defined by the inner and outer surfaces of a fluid channel having a concentric configuration.

15. Pump, A gas separation device having a housing that defines a fluid passage between an outer surface and an inner surface, wherein the housing has an inlet and an outlet extending from a first end and a second end, respectively, the first end being opposite to the second end, the inlet and the outlet being in fluid communication with the fluid passage, and thereby the gas separation device is operable by the pump to allow 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 including an inlet coupled to the outlet of the gas separation device, Includes, The aforementioned fluid channel defines the fluid channel volume, The fluid source is configured to deliver a forward flow through the gas separation device and the chromatography device, and the chromatography device is operable to allow a reverse flow through the chromatography device. The gas separation device has a forward flow of 0.001 mL through the housing. －１ ~0.51 mL －１ It is configured to show the effective air capture ratio (ATER), The ATER is a fluid system in which the ratio of the second mean fluid velocity μ2 to the first mean fluid velocity μ1 is divided by the diffuser portion volume.

16. The system according to claim 15, wherein the first mean fluid velocity μ1 used to determine the ATER is defined by the velocity of the fluid flowing through the inlet, and the second mean fluid velocity μ2 used to determine the ATER is defined by the velocity of the fluid flowing through the diffuser portion.

17. The system according to claim 15, wherein the chromatography device has a total volume defined by the volume between the fluid inlet and the fluid outlet of the chromatography device, and the fluid flow volume of the gas separation device is 50% or less of the total volume of the chromatography device.

18. The system according to claim 15, wherein the gas separation device is configured to exhibit a transition volume of five times or less the value of the fluid flow path volume of the gas separation device during the forward flow through the housing.

19. The system according to claim 15, wherein the gas separation device further includes a manifold that is in fluid communication with at least one outlet, the manifold divides the fluid exiting the outlet into a plurality of fluid passages.

20. The system according to claim 15, 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 the diffuser portion volume.

21. The system according to claim 20, wherein at least a portion of one or both of the inner and outer surfaces of the fluid channel defining the diffuser portion is translucent or transparent, so that bubbles can be observed within the diffuser portion.

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