Gas separation device

Abstract

A gas separation device for use in conjunction with a liquid chromatography system is presented. The gas separation device includes a housing defining a fluid flow path between an outer surface and an inner surface. The fluid flow path includes an inlet portion, a diffuser portion, a recombination portion, and an outlet portion. Any bubbles contained in the fluid are trapped within the diffuser portion as the fluid flows in the forward direction. Fluid flow through the gas separation device is reversible to remove trapped gas bubbles from within the gas separation device. In the operating state, fluid is delivered from the gas separation device into the waste stream to ensure that bubbles exit the liquid chromatography system. The gas separation device may exhibit an air capture efficiency ratio (ATER) of between 0.001 mL <-1 > and 0.51 mL <-1 > during the flow of the fluid in the forward direction.

Description

Technical Field

[0001] The present disclosure relates generally to gas separation apparatus and methods, and more particularly to gas separation apparatus and methods for liquid chromatography systems. Background Art

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

[0003] When delivering fluids containing molecules of interest and other fluids used in a chromatographic device, air bubbles may be introduced into the system. When air bubbles are introduced into the system it is generally detrimental to the function of the liquid chromatography device and it is desirable to reduce these situations. Summary of the invention

[0004] In a first example ("Example 1"), a gas separation device includes a shell defining a fluid flow path between an outer surface and an inner surface, the shell having an inlet connected to the fluid flow path and an outlet connected to the fluid flow path, the shell being operable to allow fluid to flow from the inlet to the outlet in a forward direction and from the outlet to the inlet in a reverse direction. The fluid flow path defines a fluid path volume and includes an inlet portion, the inlet portion being configured to receive fluid from the inlet during fluid flow through the shell in a forward direction, the inlet portion defining an inlet portion volume; a diffuser portion, the diffuser portion being configured to receive fluid from the inlet portion during fluid flow through the shell in a forward direction, the diffuser portion defining a diffuser portion volume; a recombination portion, the recombination portion being configured to receive fluid from the diffuser portion during fluid flow through the shell in a forward direction, the recombination portion defining a recombination portion volume; and an outlet portion, the outlet portion being configured to receive fluid from the recombination portion during fluid flow through the gas separation device in a forward direction, the outlet portion defining an outlet portion volume. During fluid flow through the shell in a forward direction, the gas separation device is configured to exhibit a flow rate of 0.001 mL / min at 0.001 mL / min. -1 To 0.51mL -1 Air capture efficiency ratio (ATER) between .

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

[0006] In a third example ("Example 3"), the apparatus of Example 1 includes wherein the gas separation apparatus further includes a fluid flow path leading away from the outlet.

[0007] In a fourth example ("Example 4"), the apparatus of Example 1 further includes the gas separation apparatus further including a manifold in fluid communication with the outlet, the manifold dividing the fluid exiting the outlet into a plurality of fluid flow paths.

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

[0009] In a sixth example ("Example 6"), the apparatus of Example 1 includes wherein the inlet portion volume and the diffuser portion volume combined account for between 10% and 75% of the fluid path volume.

[0010] In a seventh example ("Example 7"), the apparatus of Example 1 includes wherein a first average fluid velocity for determining the ATER is defined by a velocity of the fluid flowing through the inlet, and a second average fluid velocity for determining the ATER is defined by a velocity of the fluid flowing through the diffuser portion.

[0011] In an eighth example ("Example 8"), the apparatus of Example 7 also includes wherein ATER is defined by a ratio of the second average fluid velocity to the first average fluid velocity divided by the diffuser portion volume.

[0012] In a ninth example (“Example 9”), the apparatus of Example 1 also includes wherein at least one of the inner surface and the outer surface of the diffuser portion defines a generally dome-shaped longitudinal profile.

[0013] In a tenth example (“Example 10”), the apparatus of Example 1 also includes wherein at least one of the inner surface and the outer surface of the diffuser portion defines a substantially flat longitudinal profile.

[0014] In an eleventh example (“Example 11”), the apparatus of Example 1 also includes wherein at least one of the inner surface and the outer surface of the diffuser portion defines a conical profile or a frusto-conical profile.

[0015] In a twelfth example ("Example 12"), the apparatus of Example 1 also includes wherein at least a portion of the housing is translucent or transparent such that the volume of gas in the diffuser portion can be observed through the housing.

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

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

[0018] In a fifteenth example ("Example 15"), the device of Example 1 also includes wherein the reorganization portion is defined by an inner surface and an outer surface of the fluid flow path having a concentric configuration.

[0019] In a sixteenth example ("Example 16"), a fluid system includes a gas separation device having a housing defining a fluid flow path between an outer surface and an inner surface, the housing having an inlet connected to the fluid flow path and an outlet connected to the fluid flow path, the housing being operable to allow fluid to flow from the inlet to the outlet in a forward direction and to flow in a reverse direction, and the fluid flow path defining a fluid path volume. The system also includes a fluid source coupled to the inlet of the gas separation device and at least one chromatographic device including 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 chromatographic device, and the chromatographic device being operable to allow a reverse flow through the chromatographic device, and wherein the gas separation device is configured to exhibit a flow rate of 0.001 mL during forward flow through the housing. -1 To 0.51mL -1 Air capture efficiency ratio (ATER) between .

[0020] In a seventeenth example (“Example 17”), the system of Example 16 also includes a first average fluid velocity for determining the ATER defined by a velocity of the fluid flowing through the inlet, and a second average fluid velocity for determining the ATER defined by a velocity of the fluid flowing through the diffuser portion, and wherein the ATER is defined by a ratio of the second average fluid velocity to the first average fluid velocity divided by a volume of the diffuser portion.

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

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

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

[0024] In a twenty-first example ("Example 21"), the system of Example 16 includes wherein the fluid flow path includes: an inlet portion, the inlet portion being configured to receive fluid from the inlet during forward flow through the shell; a diffuser portion, the diffuser portion being configured to receive fluid from the inlet portion during forward flow through the shell, the diffuser portion defining a diffuser portion volume; a recombination portion, the recombination portion being configured to receive fluid from the diffuser portion during forward flow through the shell; and an outlet portion, the outlet portion being configured to receive fluid from the recombination portion during forward flow through the gas separation device.

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

[0026] In a twenty-third example ("Example 23"), a method for capturing and releasing the volume of bubbles within a gas separation device is provided, the gas separation device having a shell, the shell defining a fluid flow path having an outer surface and an inner surface, the shell having an inlet in fluid communication with the fluid flow path and an outlet in fluid communication with the fluid flow path, the method comprising: delivering a fluid through the flow path in a forward direction so that the fluid flows from the inlet through the gas separation device to the outlet. The method also 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 shell is translucent so that the volume of the gas can be observed; and stopping the delivery of the fluid through the fluid flow path. The method also includes delivering a fluid through the fluid flow path in a reverse direction so that the fluid flows from the outlet to the inlet to remove at least a portion of the volume of bubbles from the gas separation device.

[0027] In a twenty-fourth example ("Example 24"), the method of Example 23 also includes wherein the fluid flow path includes: an inlet portion, the inlet portion is configured to receive fluid from the inlet during the fluid flowing through the shell in a forward direction; a diffuser portion, the diffuser portion is configured to receive fluid from the inlet portion during the fluid flowing forward through the shell, the diffuser portion defining a diffuser portion volume; a recombination portion, the recombination portion is configured to receive fluid from the diffuser portion during the fluid flowing forward through the shell; and an outlet portion, the outlet portion is configured to receive fluid from the recombination portion during the fluid flowing forward through the gas separation device.

[0028] In a twenty-fifth example (“Example 25”), the method of Example 24 also includes where capturing the volume of gas bubbles includes capturing the volume of gas bubbles within a diffuser portion of the gas separation device.

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

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

[0031] In a twenty-eighth example ("Example 28"), the method of Example 23 also includes wherein during the forward flow of the fluid through the housing, the gas separation device exhibits a flow rate of 0.001 mL -1 and 0.51mL -1 Air capture efficiency ratio (ATER) between .

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

[0033] In a thirtieth example (“Example 30”), the method of Example 24 also includes wherein a volume of the gas bubbles is between 1% and 100% of the volume of the fluid flow path.

[0034] In a thirty-first example ("Example 31"), the method of Example 23 also includes wherein the outlet fluid of the gas separation device is connected to the inlet of the chromatography device, so that the gas separation device and the chromatography device are arranged in series, and wherein the method also includes delivering the fluid through the outlet of the gas separation device and into the inlet of the chromatography device.

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

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

[0037] In a thirty-fourth example (“Example 34”), the apparatus of Example 32 also includes wherein at least a portion of the core has a rectangular cross-section. BRIEF DESCRIPTION OF THE DRAWINGS

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

[0039] Figure 1 is a flow chart of a chromatography system according to some embodiments;

[0040] Figure 2 shows a chromatography column for use with a gas separation device according to some embodiments;

[0041] Figure 3 A shows a side view of a plurality of chromatography columns for use with a gas separation device according to some embodiments;

[0042] Figure 3B shows a side view of a plurality of chromatography columns for use with a plurality of gas separation devices according to some embodiments;

[0043] Figure 4 According to some embodiments Figure 2 An enlarged view of a gas separation device;

[0044] Figure 5 According to some embodiments Figure 4 An exploded view of a gas separation device;

[0045] Figure 6 According to some embodiments Figure 4 A cross-sectional view of a gas separation device;

[0046] Figure 7 According to some embodiments Figure 4 A cross-sectional view of a flow profile of a gas separation device;

[0047] Figures 8A-8F A schematic diagram showing a gas separation device as gas bubbles are delivered through the gas separation device according to some embodiments;

[0048] Figures 9A-9F A schematic diagram showing a gas separation device as gas bubbles are delivered through the gas separation device according to some embodiments;

[0049] Figures 10A-10FA cross-sectional view showing a flow profile of a gas separation device according to some embodiments;

[0050] Fig.11 shows expected transition curves for different designs of the gas separation device described in Reference Example 1 according to some embodiments;

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

[0052] Fig.13 According to some embodiments, Fig.12 The expected transition curve at the outlet of the gas separation device after the introduction of the salt solution is shown;

[0053] Figures 14A-14W shows cross-sectional views of 23 designs of a gas separation device as described in Reference Example 1 according to some embodiments;

[0054] Figures 15A-15C A schematic diagram showing a gas separation device after the introduction of bubbles as described in Reference Example 2 according to some embodiments; and

[0055] Fig.16 A transition chromatogram associated with the data in Table 2 of Example 2 is shown according to some embodiments. DETAILED DESCRIPTION

[0056] Those skilled in the art will readily appreciate that aspects of the present disclosure may be implemented by any number of methods and devices configured to perform the intended functions. It should also be noted that the drawings referenced herein are not necessarily drawn to scale, but may be enlarged to illustrate various aspects of the present disclosure, and the drawings should not be construed as limiting in this regard. It will be understood that, as used herein, the term "on" means that an element such as a polymer film is directly on another element, or there may be intermediate elements.

[0057] Figure 1 8 is a flow chart of a liquid chromatography system 8 according to some embodiments. The liquid chromatography system 8 can be an affinity chromatography system for separating molecules from a liquid. However, various other types of chromatography and related systems can be used together with the gas removal concept described herein, including but not limited to column chromatography, ion exchange chromatography, dye ligand (affinity) chromatography, adsorption column 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 collecting section 18, a waste stream 20, a data acquisition device 22, a gas separation device 24 and at least one chromatographic device 26.

[0058] As shown, the fluid source 10 is configured to deliver the fluid mixture into the first syringe 12a, which is then delivered into (one or more) pumps 14. In some embodiments, the first syringe 12a is configured to inject analytes and / or other molecules into the liquid delivered from the fluid source 10. The first syringe 12a can inject these analytes and / or other molecules into the liquid before the liquid passes into (one or more) pumps 14 from the fluid source 10. Further, in some embodiments, the second syringe 12b is configured to inject analytes and / or other molecules into the fluid mixture after the fluid mixture has left (one or more) pumps 14. In some embodiments, the liquid chromatography system 8 includes both the first syringe 12a and the second syringe 12b, while in other embodiments, the liquid chromatography system 8 may include only one of the first syringe 12a and the second syringe 12b.

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

[0060] After passing through the chromatographic device 26, the fluid mixture is delivered to the detector 16, which is configured to analyze the separated target analytes and / or other molecules of the fluid mixture, and the fluid mixture can be collected into a single collection container 18 or multiple collection containers (not shown) using a single collection container 18 or multiple collection containers (not shown), and the byproducts or fluids of the solution that are not target molecules can be delivered from the detector 16 to a waste stream (waste stream) 20. Figure 1 In the illustrated embodiment, the liquid chromatography system 8 includes one detector 16, however, in some embodiments, the liquid chromatography system 8 may include at least one detector 16. After passing through the detector(s) 16, in some embodiments, information acquired from the detector(s) 16 based on the characteristics 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 characteristics of the mixture passing through the chromatography device 26.

[0061] Figure 2 An example of a chromatographic device 27 is shown, which can be used in combination with a chromatographic device 26 in a liquid chromatography system 8. As shown, a housing 28 surrounds a chromatographic device 26 (not shown), and the chromatographic device has an inlet portion 30 and an outlet portion 32 extending from the housing 28. The inlet portion 30 is positioned on a side opposite to the outlet portion 32. A chromatographic device, such as (one or more) chromatographic devices 26, defines or can contain a total volume. The total volume is defined by the volume (also referred to as the internal volume or fluid volume) between the inlet portion 30 and the outlet tube 34 of the chromatographic device, such as the chromatographic device 26 (not shown). More specifically, the volume includes the functional bed volume of the chromatographic device and the volume of any channels, pipes or other connectors associated with the chromatographic device, and the functional bed volume is defined as the volume that can accommodate or maintain the fluid during the separation process.

[0062] Although the chromatographic device 26 and its features discussed herein are provided by way of example, in some embodiments, the chromatographic device 26 of the liquid chromatography system 8 may adopt various other configurations based on the desired functionality and the target process being used. In some embodiments, the chromatographic device 26 is similar to the chromatographic device described in PCT / US21 / 049969 by Clinger et al., entitled “AFFINITY CHROMATOGRAPHY DEVICES CONTAINING A FIBRILLATED POLYMER MEMBRANE AND MANIFOLDS CONTAINING THE SAME”. In any case, the chromatographic device 26 may include an inlet tube at the inlet portion 30. The outlet tube 34 may extend from the outlet portion 32 and be fluidically connected to the outlet portion 32. Although the liquid chromatography system 8 and Figure 2 Depicted as including only one chromatographic device 26, but in some embodiments, multiple chromatographic devices, such as chromatographic device 26, can be combined. For example, two or more chromatographic devices can be combined, each chromatographic device having a similar or different configuration as desired. The chromatographic device including (one or more) chromatographic devices 26 can be connected together at its inlet through a distributor or manifold, that is, connected to the gas separation device 24 in turn. In other words, the gas separation device 24 can provide services for one or more chromatographic devices. Therefore, although it is referred to as a single chromatographic device, such as chromatographic device 26, in some embodiments, this can refer to multiple chromatographic devices, such as multiple chromatographic devices 26, connected together at its inlet.

[0063] Figure 3A shows this variation of the chromatographic device 26, wherein the chromatographic device 26 includes at least four chromatographic devices located within a housing 28 and fluidically connected to the gas separation device 24. More specifically, as shown, the chromatographic device 26 includes a first manifold 6a connected to a first chromatographic device 26a and a second chromatographic device 26b, and a second manifold 6b connected to a third chromatographic device 26c and a fourth chromatographic device 26d. Thus, a plurality of manifolds 6 can be arranged in parallel. The ability to utilize at least two parallel manifolds advantageously allows for increased volume capacity while using the chromatographic device described herein. In other words, a configuration having a plurality of chromatographic devices 26a-d eliminates the need to move to a chromatographic device with a larger volume. In addition, as Figure 3 As depicted in Figure 2A, placing the manifolds in parallel reduces concerns about over-pressurizing the chromatography device 26. In further embodiments, the liquid chromatography system 8 may incorporate four or more chromatography devices.

[0064] Further, in some embodiments, the liquid chromatography system 8 may incorporate more than one chromatography device 26 in combination with more than one gas separation device 24. For example, Figure 3B A liquid chromatography system 8 ( Figure 1 ), wherein the chromatographic device 26 includes a first chromatographic device 26a and a second chromatographic device 26b arranged in parallel. Each of the first chromatographic device 26a and the second chromatographic device 26b is connected to a gas separation device. Exemplarily, the first chromatographic device 26a is fluidically connected to the first gas separation device 24a, and the second chromatographic device 26b is fluidically connected to the second gas separation device 24b. Further, the inlet pipe 40a of the first gas separation device 24a and the inlet pipe 40b of the second gas separation device 24b are each connected to the first manifold 6a, so that the fluid can be taken from the fluid source 10( Figure 1 ) is delivered by manifold 6a and delivered in parallel to gas separation devices 24a, 24b and chromatographic devices 26a, 26b. Similarly, the outlet portion 32a of the first chromatographic device 26a and the outlet portion 32b of the second chromatographic device 26b can be connected with the second manifold 6b fluid so that the fluid is merged into a single fluid path after it is delivered through the chromatographic devices 26a, 26b. Although two gas separation devices are shown, any number of gas separation devices can be combined. For example, liquid chromatography system 8 can include three or more gas separation devices and three or more chromatographic devices for being attached to the gas separation devices.

[0065] Figure 4 An enlarged view of a gas separation device 24 coupled to an inlet portion 30 of a chromatographic device (not shown) within a chromatographic apparatus 27 is shown. The gas separation device 24 includes an inlet tube 40 coupled to an outer housing 50. As will be seen in reference Figure 4-6As further described, the inlet tube 40 and the outer shell 50 are configured to receive a fluid which then extends through the outer shell 50 and passes through at least one outlet 44 ( Figure 4 ). After passing through the at least one outlet 44, the fluid may be delivered to the chromatographic device 26. More specifically, the at least one outlet 44 is coupled to the inlet portion 30 of the chromatographic device 26, such that the gas separation device 24 and the chromatographic device 26 are coupled in series with each other. More specifically, the at least one outlet 44 may be fluidly coupled to a channel and / or conduit that is fluidly coupled to an inlet tube (not shown) of the chromatographic device 26. In some embodiments, the at least one outlet 44 may be fluidly coupled to a manifold, such as the manifold 6A ( Figure 3 A) is connected to the channel fluid of the gas separation device 24 to distribute the fluid to multiple chromatographic devices 26. Further, in other embodiments, at least one outlet 44 can be directly connected to the accessories and inlet tubes of the chromatographic device 26. The channel of the fluid through the gas separation device 24 will be referred to herein as Figure 5 and 6 Further description.

[0066] Figure 5 An exploded view of the gas separation device 24 is shown. As shown, the gas separation device 24 includes an inlet pipe 40 coupled to a top portion 42, an outer shell 50, an internal component 60 for being received within the outer shell 50, a plurality of seals 66, and a connector ring 68 for assembling the gas separation device 24. The inlet pipe 40 includes an opening 36 extending into a center portion 38. The center portion 38 is connected to the top portion 42, which can define a portion of the outer shell 50 of the gas separation device 24. The inlet pipe 40 can be defined as being generally cylindrical, such that the inlet pipe 40 includes a circular cross-section. However, various other configurations can be implemented, and all configurations are considered to be within the scope of the present disclosure. Further, the top portion 42 can be defined by a circular or disc-shaped shape, such as Figure 5As shown in the illustrative embodiment of , however, various other configurations may be implemented. For example, in some embodiments, the inlet tube 40 and / or the top portion 42 may have a rectangular shape, a triangular shape, or any other applicable configuration. Further, the inlet tube 40 and the top portion 42 may be composed of a transparent or translucent material. For example, the inlet tube 40 and / or the top portion 42 may be composed of a transparent or translucent polymer, such as a cyclic olefin copolymer (COC) or an acrylic polymer. However, various other applicable transparent or translucent materials may be used to form the inlet tube 40 and / or the top portion 42. In this article, "transparent" may be defined as allowing light to pass directly through the material. In this article, "translucent" may be defined as allowing only a portion of the light irradiated on the material to pass through the material. In some embodiments, the inlet tube 40 may not be transparent or translucent, while the top portion 42 is transparent or translucent. In other embodiments, only a portion of the top portion 42 is transparent or translucent. Whether transparent or translucent, as will be further described herein, the material of inlet tube 40 and / or top portion 42 is selected so that bubbles positioned vertically below top portion 42 can be visually observed from outside gas separation device 24 (e.g., with the naked eye under natural or artificial lighting).

[0067] Continue to refer Figure 5 , the inner component 60 will be further described. The inner component 60 includes a top surface 62 and a core 64 extending below the top surface 62, and the "top surface" is also referred to as the "diffuser surface" in this document. Figure 6 As best shown in the cross-sectional view of FIG. 1 , the top surface 62 may include a longitudinal profile extending along the longitudinal axis L having a generally dome-shaped profile. A “generally dome-shaped profile” may be defined herein as a top surface 62 having a dome-shaped or curved shape, wherein the top surface 62 has a maximum vertical height disposed generally within the longitudinal center of the top surface 62, and wherein the vertical height of the top surface 62 decreases as the top surface 62 extends outward from the longitudinal center. In other embodiments, such as Fig.14H As shown in the modified gas separation device 924 of FIG. 1 , the top surface 62 can have a substantially flat / flat longitudinal profile. In other words, the top surface 62 can have a vertical height that is substantially constant over the width and longitudinal extent of the top surface 62. Further, various other longitudinal profiles can be combined, for example, a truncated cone and / or a tapered longitudinal profile can be implemented. However, regardless of the profile of the top surface 62, as shown in FIG. Figure 5 and 6As shown, the top surface 62 of the internal component 60 extends to a vertical height less than the lowest vertical height of the central portion 38 of the inlet pipe 40. This is beneficial so that when the fluid may be delivered through the gas separation device 24 in the opposite direction, the fluid will leave the inlet pipe 40, rather than being captured above the top surface 62 and near the inlet pipe 40. Further, the core 64 may define a substantially annular cross-sectional shape. However, various other configurations may be implemented. For example, the core 64 may be defined by a rectangular, triangular, elliptical, polygonal or irregular shape. The above examples are not intended to be limiting, and any shape of the core 64 applicable may be incorporated into the gas separation device. Further, 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 other embodiments, the core 64 may include three or more cross-sectional shapes.

[0068] Still refer to Figure 5 , the outer shell 50 of the gas separation device 24 will be further described. The outer shell 50 includes a base 52, a cavity 54 extending in the base 52 and defined by an outer wall 56, and at least one outlet 44 extending from the bottom portion of the base 52. Exemplarily, the outer wall 56 includes a plurality of grooves 59 extending circumferentially in the outer wall 56 of the base 52 for receiving a plurality of seals 66 and a connector ring 68. The outer shell 50 can be composed of a polymer material, such as polypropylene, polyetheretherketone (PEEK), cyclic olefin copolymer, polycarbonate, or any other suitable polymer material. In other embodiments, the outer shell 50 can be composed of a metal material or various other applicable materials. The base 52 has a substantially circular cross-section, but the base 52 can implement various other shapes. Further, as shown, a plurality of seals 66 include a first seal 66a and a second seal 66b for receiving in the groove 59 of the outer wall 56. In some embodiments, the plurality of seals 66 are O-ring seals, but various other types of seals can be implemented. Additionally, the connector ring 68 is shown as having a generally C-shape, however various other configurations and / or shapes of the connector ring 68 may be incorporated and are considered to be within the scope of the present disclosure.

[0069] refer to Figure 6, the assembled gas separation device 24 will be further described herein. As shown, the top portion 42 of the inlet tube 40 is shown as being coupled to the base 52 of the outer shell 50. More specifically, the top portion 42 is coupled within a groove 59 of a wall 56 of the outer shell 50. As shown, the generally dome-shaped profile of the top portion 42 can match the generally dome-shaped profile of the top surface 62 of the inner component 60 to form a spacer extending between the top portion 42 and the top surface 62. A connector ring 68 engages with the base 52 and is positioned above the top portion 42 to secure the positioning of the top portion 42 within the base 52. During assembly of the gas separation device 24, a plurality of seals 66, exemplarily O-ring seals, can be used to ensure fluid sealing within the gas separation device 24. Specifically, the seal 66 can contribute to the fluid sealing between the inner component 60, the top surface 62 and the base 52. Further, the inner component 60 is positioned within the cavity 54 so that the central axis C of the inner component 60 is aligned with the central axis D of the inlet tube 40. This allows the inner component 60 to be spaced apart from the outer wall 56 of the base 52 and form a concentric spacer between the inner component 60 and the outer wall 56 of the base 52. Therefore, the core 64 of the inner component 60 can be defined by an annular shape. In other words, the inner component 60 is centrally located within the outer shell 50. However, in other embodiments, the central axis C of the inner component 60 can be laterally offset from the central axis D of the inlet tube 40. In this way, the fluid can flow through the spacer between the inner component and the inner surface of the outer shell 50.

[0070] Below the inner member 60, the base 52 includes a collector 58, which is defined as an area for connecting the spacer extending between the inner member 60 and the outer wall 56 of the base 52. Further extending from the collector 58 is at least one outlet 44, illustratively a first outlet 44a and a second outlet 44b, which extend outwardly and can be connected to the inlet portion of the chromatography device 26 ( Figure 3 A). Although shown as two outlets 44a, 44b, the at least one outlet 44 may include one, two, three, four or more outlets. Figure 6 and Figure 7 As further described, the spacing within the inlet tube 40 , the spacing between the top surface 62 and the top portion 42 , and the spacing between the inner member 60 and the base 52 define a fluid flow path that allows fluid to pass through the gas separation device 24 .

[0071] More specifically, and with reference to Figure 6 and Figure 724, a cross-sectional view of the fluid flow profile of the device 24 is shown, and a fluid flow path 70 is formed to extend through the gas separation device 24. The fluid flow path 70 includes an inlet portion 72, a diffuser portion 74, a reorganization portion 76, and an outlet portion 78. As shown, the fluid flow path 70 extends from the opening 36 of the inlet tube 40, downwardly through the central portion 38 of the inlet tube 40 and into the space between the top surface 62 and the top portion 42. In this manner, the inlet tube 40 defines an inlet portion 72 of the fluid flow path 70 extending through the inlet tube 40. When the fluid flows through the inlet portion 72 of the fluid flow path 70, the fluid defines a first average velocity μ1.

[0072] After extending through the inlet portion 72, the fluid flow path 70 extends into the space between the top surface 62 and the outer shell 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 manner, the fluid flow path 70 defines a diffuser portion 74 that extends vertically between the top surface 62 and the top portion 42 and extends laterally within the outer shell 50. Within the diffuser portion 74, the velocity of the fluid traveling through the fluid flow path 70 is reduced and defined by the second average velocity μ2 as the fluid flow collides with the top surface 62 and changes the flow direction.

[0073] Further, as shown, the fluid flow path 70 can extend downward through the spacer between the core 64 of the inner component 60 and the outer wall 56 of the base 52 of the outer shell 50. In this manner, the fluid delivered through the fluid flow path 70 is dispersed into a plurality of fluid paths and extends downward to the collector 58. Thus, the fluid flow path 70 can define a recombination portion 76 extending between the top surface 62 of the inner component 60 and the bottom portion of the collector 58. In some embodiments, the recombination portion 76 is defined by an annular continuous spacer extending around the inner component 60. In other embodiments, the recombination portion 76 can be defined by a plurality of discrete channels extending around the core 64 of the inner component 60.

[0074] Due to the concentric configuration of the inner component 60 and the base 52 of the outer shell 50, any fluid path through which the fluid may travel around the inner component 60 is the same distance from the top surface 62 and the collector 58. This allows the fluid flow to maintain plug flow through the fluid flow path 70 and ensures that fluid molecules that come together before contacting the top surface 62 recombine at the collector 58. In other words, the configuration of the inner component 60 allows for fluid flow that reduces the amount of mixing within and / or between fluids.

[0075] As shown, once the fluid passes through collector 58, the fluid may extend into at least one outlet 44 to exit gas separation device 24. Thus, fluid flow path 70 defines an outlet portion 78 extending vertically between the bottom of collector 58 and exiting gas separation device 24.

[0076] The above-mentioned parts of the fluid flow path 70 are defined by the fluid path volume, which may also be referred to herein as the hold-up volume of the gas separation device 24. In other words, both the fluid flow path volume and the hold-up volume are measured as the fluid flow volume that can extend through the gas separation device 24, which is the sum of the volumes of the above-mentioned parts of the fluid flow path 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. Further, the amount of space defined between the top surface 62 and the top portion 42 defines the diffuser volume of the diffuser portion 74. Similarly, the volume of the spacer between the top surface 62 and the bottom of the collection portion 58 defines the reorganization portion volume. Finally, the volume of at least one outlet 44, illustratively the sum of the volumes of the outlet 44a and the outlet 44b, defines the outlet portion volume. As previously described, the fluid flow path volume is defined by the sum of each of the inlet portion volume, the diffuser portion volume, the reorganization portion volume, and the outlet portion volume. In some embodiments, the inlet portion volume and the diffuser portion volume together account for between 10% and 75% of the fluid path volume. Further, the inlet portion volume and the diffuser portion volume combined may account for between 35% and 50% of the volume of the fluid path. However, various other volume ratios between the various portions of the fluid flow path 70 may be combined (included). For example, the outlet portion volume may be between 5% and 75% of the volume of the fluid path. In other embodiments, the outlet portion volume may be between 10% and 75% of the volume of the fluid path.

[0077] As will be further described with reference to the test method (test method) and examples, the gas separation device 24 is configured such that: if a certain volume of bubbles is contained in the fluid delivered forward through the fluid flow path 70, then when the fluid passes through the diffuser portion 74, the volume of bubbles will be captured within the diffuser portion 74 and between the top surface 62 and the top portion 42. The forward direction is defined as the fluid extending from the inlet portion 72 to the outlet portion 78. As the fluid flows through the fluid flow path 70 in this direction, any volume of bubbles will continue to be captured within the diffuser portion 74. The operator can actuate 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 that is used to provide the liquid chromatography system 8 with instructions. Figure 1) to actuate the liquid chromatography system 8 to stop the flow of fluid through the gas separation device 24 in the forward direction and then reverse the flow of fluid through the gas separation device 24 so that the fluid is delivered from the outlet portion 78 through the gas separation device 24 to the inlet portion 72. The reverse flow through the fluid flow path 70 causes at least a portion of the volume of the bubbles to exit through the inlet tube 40 of the gas separation device 24. Thus, the reversal of the flow causes at least a portion of the volume of the bubbles trapped within the diffuser portion 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 stream 20 to ensure that the bubbles leave the liquid chromatography system 8 and are not reintroduced into the gas separation device 24.

[0078] Because at least the top portion 42 is transparent or translucent, the operator can see the volume of bubbles trapped in the diffuser portion 74 and can see the volume of bubbles removed from the diffuser portion 74. In this way, the operator can monitor the gas separation device 24 to stop and reverse the flow when the desired volume of bubbles is seen to be trapped in the gas separation device 24. For example, in some embodiments, the operator can monitor the gas separation device 24 and stop the flow once the volume of the bubbles reaches the maximum volume of the bubbles, which can be defined as at least 95% of the volume of the diffuser portion 74. In addition, the fluid can be delivered in reverse flow for a varying amount of time, which is controlled by the operator. For example, the fluid flow can be reversed until the volume of the trapped gas between at least 1% and 100% is removed from the diffuser portion 74. In some embodiments, the fluid flow reverses until at least 25% of the volume of the bubbles is removed from the diffuser portion 74.

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

[0080] As described above, the gas separation device 24 provides the advantage of being able to efficiently capture bubbles within the gas separation device 24 and easily reverse the fluid flow to remove the captured bubbles from the gas separation device 24. As will be further described with reference to the test methods and examples, the ability of the gas separation device 24 to capture bubbles can be quantified by the air capture efficiency ratio (ATER). The ATER is calculated by dividing the ratio of the second average velocity μ2 to the first average velocity μ1 by the volume of the diffuser portion. The gas separation device 24 is configured such that when the fluid flows through the gas separation device 24 in a forward direction, the ATER ranges from about 0.001 mL to about 0.1 mL. -1To about 0.51mL -1 When the ATER is maintained within the above range, the gas separation device 24 can capture bubbles from the fluid passing through the fluid flow path 70, trap the bubbles in the diffuser portion 74, and release the bubbles when the fluid flows through the fluid flow path 70 in the reverse direction.

[0081] Another advantage of the gas separation device 24 is that the transition volume of the fluid delivered through the gas separation device 24 and / or the chromatographic device 26 is reduced. More specifically, when a first fluid is inserted through the gas separation device 24 and a second fluid is subsequently 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, which is approximately equal to or less than five times the value of the fluid path volume of the gas separation device 24. In some embodiments, the transition volume can be less than or equal to five times the value of the fluid path volume. Further, when calculated with reference to the transition volume flowing through both the gas separation device 24 and the chromatographic device 26, the transition volume can be equal to or less than five times the total volume of the gas separation device 24 and the chromatographic device 26. Another advantage of the gas separation device 24 is that the device 24 is configured so that the fluid flow volume of the gas separation device 24 is less than or equal to 50% of the total volume of the chromatographic device 26. For example, in some embodiments, the fluid flow volume of gas separation device 24 may be between approximately 1% and 50% of the total volume of chromatography device 26. However, various other ratios of fluid flow volumes of gas separation device 24 to chromatography device 26 may be implemented.

[0082] Those skilled in the art will readily appreciate that aspects of the present disclosure may be implemented by any number of methods and devices configured to perform the intended functions. It should also be noted that the drawings referenced herein are not necessarily drawn to scale, but may be enlarged to illustrate various aspects of the present disclosure, and in this regard the drawings should not be interpreted as limiting. Test methods Method for simulating the flow of a liquid through a device

[0083] Computational fluid dynamics (CFD) models are developed in commercial solvers. Fluid flow solvers are based on the finite volume method, where the flow domain is divided into smaller volumes, also called cells, and the governing equations are solved at the centroid of each cell. The governing equations are further introduced and discussed in this article. By solving the governing equations, the fluid velocity in three directions, fluid pressure, salt concentration, and turbulence variables at each cell are calculated. As mentioned earlier, Figure 6 A cross-sectional view of a gas separation device 24 including a fluid path modeled using computational fluid dynamics (CFD) is shown, and Figure 7A cross-sectional view of a gas separation device 24 is shown, showing a schematic fluid domain of the gas separation device 24. As experimental methods herein may be 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 is calculated by solving the Reynolds-averaged Navier Stokes equations including conservation of mass and momentum. The shear stress transport k-omega model is used to predict the fluid turbulence through the fluid flow path.

[0085] The conservation equations for mass and momentum are given below: Mass Conservation Equation Momentum equation where ρ is the density, v is the mean velocity, p is the mean pressure, I is the identity tensor, T is the mean viscous stress tensor, and f b is the resultant force of the body forces (such as gravity), T RANS is the stress tensor.

[0086] At the inlet portion 72 ( Figure 6-7 ) defines a constant mass flow rate. The outlet is fixed at zero gauge pressure. The assumption of incompressibility is considered for the liquid and an ideal gas is considered for the air. The properties used for these methods include the properties of water and air in the liquid and gas phases, respectively. The density of the liquid is set to 997.561 kg / m 3 (kg / m3), viscosity is set to 8.8871Pa-s (Pascal seconds). The interfacial surface forces are modeled as volume forces using the continuous surface force (CSF) method of Brackbill et al. (Brackbil, JU, Kothe, DB and Zemach, C, 1992 "A Continuum method for modeling surface tension", Journal of Computational Physics (J. Comp. Physics), 100, pp. 335-354). The surface tension constant between liquid and gas is fixed to 0.072N / m (Newton / meter). However, various other surface tension and density values ​​can also be used to simulate desired fluid and material properties. Method for simulating the performance of air bubbles passing through a device and determining air capture efficiency parameters in the simulation

[0087] The volume of fluid (VOF) multiphase model is used to predict the air and liquid interfaces within the gas separation device 24. The distribution of the phases (air and liquid) and the location of the interface are given by the phase volume fractions α i The field description of V is shown below. i is the volume of the ith phase in the cell, and V is the volume of the cell.

[0088] The volume fractions of all phases in a cell must add up to 1, as determined by the following formula, where N is the total number of phases.

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

[0090] The results of the simulated liquid flow through the device are used as the initial conditions for the bubble simulation. Initially, there is only water at a fixed flow rate through the gas separation device 24. 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 volume expansion in the simulated gas separation device 24. This expansion will affect fluid flow characteristics such as velocity, pressure drop, residence time, mixing, drag, and surface tension.

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

[0093] Here, u2 is the average fluid velocity inside 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 due to increasing air capture efficiency ratio (ATER). If ATER is above a critical value, bubbles will pass through the gas separation device 24. ATER can be reduced by increasing the volume of the diffuser section 74. However, reducing ATER below a critical value does not affect the bubble capture performance.

[0095] For example, Figures 8A-8F The gas separation device 24 or a slight variation thereof is shown to have approximately 0.938 mL -1 ATER and simulate it in the simulated time state. Figures 8A-8F As shown, when fluid flows through the fluid flow path 70 of the gas separation device 24 and gas bubbles 80 are delivered into the system, the gas bubbles 80 travel through the entire gas separation device 24 and are not trapped within the diffuser portion 74 of the gas separation device 24. Specifically, Fig. 8AThe simulation is shown at a simulation time point approximately 0.1 seconds after the bubble 80 is delivered to the inlet portion 72 . Figure 8B 8 shows a simulation within the gas separation device 24 at a simulation time point of approximately 0.2 seconds after the gas bubble 80 is delivered to the inlet portion 72. Figures 8A-8F Illustratively, the air bubble 80 is positioned within the diffuser portion 74. Further, Figure 8C The simulation is shown at a time point approximately 0.3 seconds after delivery of the bubble 80. As shown, the bubble has passed through the diffuser portion 74 and moved to the reorganization portion 76. Fig.8D and Fig. 8E Gas bubbles 80 are shown positioned within the diffuser section 74 , the reforming section 76 , and the outlet section 78 of the gas separation device 24 . Figure 8F The system is shown at a point in time of approximately 0.1 seconds after the gas bubble 80 is delivered to the inlet portion 72, at which point the gas bubble 80 has passed through the entire gas separation device 24. Figures 8A-8F It is shown that the gas bubbles 80 are not captured only in the diffuser portion 74 , but pass through the entire gas separation device 24 .

[0096] Figures 9A-9F A simulation method is shown, in which the gas separation device 24 is simulated to have approximately 0.116 mL -1 As shown, gas bubbles 80 are delivered to the gas separation device 24 along with the fluid and are captured within the diffuser section 74. Specifically, Fig. 9B , fluid and gas bubbles 80 are shown extending into the diffuser portion 74. Although the fluid continues to flow through the gas separation device 24, Figures 9C-9F , the gas bubbles 80 are shown as remaining trapped in the diffuser portion 74 and not extending below the gas separation device 24. This is desirable for the proper function of the gas separation device 24 so that the gas bubbles 80 are not delivered to the chromatographic device 26 ( Figure 2 )middle. Method for simulating the flow transition of salt solutions through a device

[0097] Salt is introduced into the flow field as a tracer and its movement inside the gas separation device 24 is tracked by solving the convection-diffusion equation:

[0098] In the above equation, c, u and D ij are the salt concentration, fluid velocity, and the diffusivity of salt in the fluid. The above model formulation assumes that the fluid properties are not changed by the salt. Salt is introduced at the inlet boundary as a step function.

[0099] Figures 10A-10F2 shows a CFD model of the gas separation device 24 when a saline solution is inserted through the fluid flow path 70. Specifically, Fig. 10A The gas separation device 24 is shown prior to the insertion of the saline solution. Fig. 10B 2 shows a CFD model of the gas separation device 24 when a salt solution is inserted into the inlet portion 72 of the gas separation device 24. Further, Figures 10C-10D The salt solution is shown inserted further through the fluid flow path 70 of the gas separation device 24, which also shows the mixing of the fluids. Fig.10E and 10F As shown, over time and continued insertion of saline solution, mixing decreases and the fluid flow path 70 is completely consumed by saline solution.

[0100] By varying the parameters incorporated into the model, this approach can be used for a variety of different device designs. Further, the model allows the determination of transition curves, such as Fig.11 shown.

[0101] Specifically, Fig.11 Expected transition curves for three different designs of gas separation device 24 are shown. More specifically, Design 1 corresponds to Fig.14A The gas separation device 24 shown has a transition curve D, and the design 9 corresponds to Fig.14I The modified gas separation device 1024 shown in FIG. 1 shows a transition curve E, while the design 14 corresponds to Fig.14N A modified gas separation device 1524 corresponding to transition curve F. The transition curve shows the conductivity of the solution as a function of the volume of solution flowing through to illustrate the transition volume of each design. As shown, the simulated gas separation devices of designs 1 and 14 achieve steady-state conductivity based on a smaller volume than that required for design 9. The steady-state conductivity can be a set conductivity selected based on the conductivity of the second fluid simulated to be delivered through the gas separation device 24. This corresponds to a smaller transition volume for the simulated gas separation devices of designs 1 and 14 compared to the transition volume for the simulated gas separation device of design 9. Method for determining the volume to complete the transition of saline solution flow through a device

[0102] The ATER can be reduced by increasing the fluid path volume of the gas separation device, but this will result in an increase in the transition volume of the gas separation device. For chromatographic applications, a high transition volume is undesirable. Increasing the transition volume of the device may result in higher solution consumption and lower process efficiency. In order to measure the transition volume of a gas separation device in practice, a transition experiment is usually performed. A transition experiment involves pushing one fluid out of the gas separation device by introducing a new fluid. Therefore, by introducing a salt solution at the inlet boundary and using a Fig.12 The step function shown is used to perform the transition simulation. Fig.13 The expected transition curve at the outlet of the simulated gas separation device is shown. The conductivity of the salt solution and water was set to 21.5 and 0.01 mS / cm (milliSiemens / cm), respectively. The transition volume was measured when the conductivity at the outlet reached 21 mS / cm, which was determined as the steady-state conductivity. Method for experimental confirmation of air capture effectiveness

[0103] Gas separation device 24 is physically constructed according to Design 1 in Table 1 and is referred to herein as "Gas Separation Device A". Gas Separation Device A is mounted on a spiral wound manifold affinity chromatography device, as described in PCT Application No. PCT / US21 / 049969 by Clinger et al., placed in an AKTA Pilot liquid chromatography system (Cytiva, Marlborough, MA), and phosphate buffered saline (PBS) is pumped through Gas Separation Device A and the spiral wound manifold affinity chromatography device at a flow rate of 696 mL / min (milliliters per minute). Bubbles are introduced into Gas Separation Device A by removing the feed tube from the PBS buffer, and then placing the feed tube back into the PBS buffer about one second after the removal of the feed tube. After the bubbles are trapped in Gas Separation Device A for a few seconds, the liquid chromatography system pump is reversed, and the bubbles are discharged to the waste stream (waste stream) along with a small amount of PBS. Methods for experimental confirmation of transition volumes

[0104] The affinity chromatography device 26 described in PCT Application No. PCT / US21 / 049969 of Clinger et al. was placed in an AKTA Pilot liquid chromatography system (Stovan, Marlborough, MA) with or without a gas separation device A installed at the inlet of the affinity chromatography device (affinity chromatography device). Phosphate buffered saline (PBS) was pumped through the device at a flow rate of 152 mL / min, and deionized water was then pumped through the device at a flow rate of 152 mL / min. The transition volume is reported as the amount of volume (normalized to column volume) required to flow through the affinity chromatography device, with or without a gas separation device A installed at the inlet of the affinity chromatography device, to achieve a conductivity of 0.15 mS / cm at the outlet of the device, indicating a complete volume transition from PBS to water. The column volume is defined as the total volume of the chromatography device 26 ( Figure 2 ). Example Example 1: Results from computational fluid dynamics (CFD) simulation

[0105] Using the experimental method described above, a gas separation device 24 ( Figure 3 ) for a total of 24 unique, modified designs and simulated flow performance. Figures 14A-14X The cross-sectional views of the simulation designs 1-24 are shown respectively. Specifically, Fig.14A A cross-sectional view of the gas separation device 24 is shown. Fig. 14B A modified gas separation device 324 is shown having a fluid flow path 370 with a linearly shaped reorganization section 376 such that there are no indentations within the reorganization section 376 . Fig. 14C A modified gas separation device 424 is shown defining a fluid flow path 470 having a uniform diffuser portion 474 and a linear recombining portion 476. Further, Fig.14D A modified gas separation device 524 is shown having a modified fluid flow path 570 having a thinner diffuser portion 574 such that the volume of diffuser portion 574 may be smaller than diffuser portion 74 ( Fig.14A ) volume. In addition, Fig.14E A modified gas separation device 624 is shown having a modified fluid flow path 670 having a reorganization portion 674 extending linearly downward and continuing into a laterally extending portion. Fig.14F A modified gas separation device 724 is shown having a modified fluid flow path 770 having a reorganization section 776 extending linearly and laterally from a corner joining a diffuser section 774 of the gas separation device 724 .

[0106] refer to Figure 14G , showing that Fig.14E A modified gas separation device 824 of similar design is shown in FIG. Fig.14H An additional modified gas separation device 924 is shown having a modified fluid flow path 970 in which the top surface (upper surface) is adjacent to the top surface 62 ( Figure 1 ) is similar to the diffuser portion 974, having a linear and flat profile, so that the bottom of the diffuser portion 974 is shown as having a flat profile. Further, the volume of the diffuser portion 974 is shown as being larger than the volume of the diffuser portion 74 of the gas separation device. Further, referring to Fig.14I , shows a modified gas separation device 1024 having a modified fluid flow path 1070. The modified fluid flow path 1070 is similar to the fluid flow path 470 of the gas separation device 424, but the diffuser portion 1074 has a larger volume. Fig.14J , shows a modified gas separation device 1124 having a modified flow profile 1170, wherein the diameter of the diffuser portion 1174 is approximately 90% of the diameter of the diffuser portion 74 of the gas separation device 24. In addition, Figure 14KA modified gas separation device 1224 is shown in which the diameter of diffuser portion 1274 is approximately 80% of the diameter of diffuser portion 74. Figure 14L A modified gas separation device 1324 is shown having a diffuser portion 1374 having a diameter that is approximately 70% of the diameter of diffuser portion 74. Figure 14M A modified gas separation device 1424 is shown having a diffuser portion 1474 having a diameter that is approximately 60% of the diameter of diffuser portion 74. Further, Fig.14N A gas separation device 1524 is shown having a diffuser portion 1574 having a diameter that is approximately 50% of the diameter of diffuser portion 74 .

[0107] FIG. 140 shows a modified gas separation device 1624 having a diffuser portion 1674 having a diameter that is 50% of the diameter of diffuser portion 74 while having an increased thickness. Figure 14P A modified gas separation device 1724 is shown having a diffuser portion 1774 similar to diffuser portion 1674 (FIG. 14O), but having a thickness greater than the thickness of diffuser portion 1674. Similarly, Figure 14Q and 14R Modified gas separation devices 1824, 1924 are shown, respectively, having diffuser portions 1874, 1974 having increased thickness. Further, Figure 14S and 14T Modified gas separation devices 2024, 2124 are shown, respectively, having diffuser portions 2074, 2174 having varying thicknesses and diameters. Figure 14U , 14V 14W show additional modified gas separation devices 2224, 2324 and 2424, respectively, whose respective diffuser portions 2274, 2374 and 2474 have different (varying) thicknesses and diameters.

[0108] Figure 14X A modified gas separation device 2524 is shown, which is similar in design to Fig.14F and 14G ,and Fig.14F and 14G In comparison, its overall diameter is approximately twice as large, with a curved reorganization section 2576 and a larger diffuser section 2574.

[0109] The delivery of bubbles through each of the above models was simulated. The simulation results are listed in Table 1. The results show that if the air capture efficiency ratio (ATER) is higher than 0.51 mL -1 , the bubbles pass through the corresponding gas separation device. Table 1 Summary of simulation data Example 2: Experimental confirmation of air capture effect and transition volume

[0110] Figures 15A-15C The series of time-lapse diagrams shown in are taken from still photographs and show that bubbles introduced into the gas separation device A have been seen (visualized) and removed using the appropriate (one or more) test methods described above. Fig.15A As shown, prior to the insertion of the bubble, the fluid flows through the gas separation device A, and no bubbles are shown as being trapped in the diffuser portion 74. However, during the insertion of the bubble 80, the bubble 80 is shown within the diffuser portion 74 (see FIG. Fig. 15B ), and can be observed from the outside of the gas separation device A. Further, after the fluid flows through the gas separation device A in the reverse direction, and as Fig. 15C As shown, bubbles are no longer observed in the diffuser portion 74 and the bubbles have been discharged from the gas separation device A.

[0111] Table 2 reports the transition volumes without and with gas separation device A in the flow path of the chromatographic device, determined using the experimental method(s) described above. The difference in transition volume is small, indicating that the effect of gas separation device A on the transition volume is negligible. As listed in Table 2, the transition volume of the system is maintained below 5 times the column volume without and with gas separation device A. The transition chromatograms associated with the data in Table 2 are shown in Figure 2. Fig.16 shown. Table 2 Transformation volume

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

Claims

1. A gas separation device, comprising: a housing defining a fluid flow path between an outer surface and an inner surface, the housing having an inlet in communication with the fluid flow path and an outlet in communication with the fluid flow path, the housing being operable to allow fluid to flow in a forward direction from the inlet to the outlet and in a reverse direction from the outlet to the inlet, and the fluid flow path defining a fluid path volume and having: an inlet portion configured to receive fluid from the inlet during flow of the fluid through the housing in the forward direction, the inlet portion defining an inlet portion volume; a diffuser portion configured to receive fluid from the inlet portion during flow of the fluid through the housing in the forward direction, the diffuser portion defining a diffuser portion volume; a recombination section configured to receive fluid from the diffuser section during flow of the fluid through the housing in the forward direction, the recombination section defining a recombination section volume; an outlet portion configured to receive fluid from the recombination section during flow of the fluid through the gas separation device in the forward direction, the outlet portion defining an outlet portion volume; and Wherein, during the flow of the fluid through the housing in the forward direction, the gas separation device is configured to exhibit a -1 To 0.51mL -1 Air capture efficiency ratio (ATER) between .

2. The gas separation device according to claim 1, characterized in that: The gas separation device is configured to exhibit a transition volume less than or equal to 5 times the value of the fluid flow path volume during fluid flow through the housing in a forward direction.

3. The gas separation device according to claim 1, characterized in that: The gas separation device also includes a fluid flow path leading away from the outlet.

4. The gas separation device according to claim 1, characterized in that: The gas separation device also includes a manifold in fluid communication with the outlet, the manifold dividing fluid exiting the outlet into a plurality of fluid flow paths.

5. The gas separation device according to claim 4, characterized in that: The plurality of fluid flow paths includes at least two fluid paths.

6. The gas separation device according to claim 1, characterized in that: The inlet portion volume and the diffuser portion volume combined are between 10% and 75% of the fluid path volume.

7. The gas separation device according to claim 1, characterized in that: A first average fluid velocity for determining the ATER is defined by a velocity of the fluid flowing through the inlet, and a second average fluid velocity for determining the ATER is defined by a velocity of the fluid flowing through the diffuser portion.

8. The gas separation device according to claim 7, characterized in that: The ATER is defined by the ratio of the second average fluid velocity to the first average fluid velocity divided by the diffuser section volume.

9. The gas separation device according to claim 1, characterized in that: At least one of the inner surface and the outer surface at the diffuser portion defines a generally dome-shaped longitudinal profile.

10. The gas separation device according to claim 1, characterized in that: At least one of the inner surface and the outer surface at the diffuser portion defines a substantially flat longitudinal profile.

11. The gas separation device according to claim 1, characterized in that: At least one of the inner surface and the outer surface at the diffuser portion defines a conical profile or a frusto-conical profile.

12. The gas separation device according to claim 1, characterized in that: At least a portion of the housing is translucent or transparent so that the gas volume in the diffuser portion can be viewed through the housing.

13. The gas separation device according to claim 1, characterized in that: The recombining portion is defined by a plurality of discrete channels extending between the inner and outer surfaces of the fluid flow path.

14. The gas separation device according to claim 1, characterized in that: The recombining section is defined by an annular channel extending between the inner and outer surfaces of the fluid flow path.

15. The gas separation device according to claim 1, characterized in that: The recombining portion is defined by inner and outer surfaces of the fluid flow path having a concentric configuration.

16. A fluid system comprising: a gas separation device having a housing defining a fluid flow path between an outer surface and an inner surface, the housing having an inlet in communication with the fluid flow path and an outlet in communication with the fluid flow path, the housing being operable to allow fluid to flow in a forward direction from the inlet to the outlet and in a reverse direction, and the fluid flow path defining a fluid path volume; a fluid source, the fluid source being connected to an inlet of the gas separation device; as well as at least one chromatographic device comprising an inlet coupled to an outlet of the gas separation device, the fluid source configured to deliver forward flow through the gas separation device and the chromatographic device, and the chromatographic device operable to allow reverse flow through the chromatographic device; as well as Wherein, during the forward flow of the fluid through the housing, the gas separation device is configured to exhibit a -1 To 0.51mL -1 Air capture efficiency ratio (ATER) between .

17. The system of claim 16, wherein: A first average fluid velocity for determining the ATER is defined by a fluid velocity flowing through the inlet, and a second average fluid velocity for determining the ATER is defined by a fluid velocity flowing through a diffuser section, and wherein the ATER is defined by a ratio of the second average fluid velocity to the first average fluid velocity divided by a diffuser section volume.

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

19. The system of claim 16, wherein: The gas separation device is configured to exhibit a transition volume that is less than or equal to five times a value of a fluid flow path volume of the gas separation device during forward flow of fluid through the housing.

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

21. The system of claim 16, wherein: The fluid flow path includes: an inlet portion, which is configured to receive fluid from the inlet during the forward flow of the fluid through the shell; a diffuser portion, which is configured to receive fluid from the inlet portion during the forward flow of the fluid through the shell, and the diffuser portion defines a diffuser portion volume; a recombination portion, which is configured to receive fluid from the diffuser portion during the forward flow of the fluid through the shell; and an outlet portion, which is configured to receive fluid from the recombination portion during the forward flow of the fluid through the gas separation device.

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

23. A method for capturing and releasing a volume of gas bubbles within a gas separation device, the gas separation device having a housing defining a fluid flow path having an outer surface and an inner surface, the housing having an inlet in fluid communication with the fluid flow path and an outlet in fluid communication with the fluid flow path, the method comprising: delivering a fluid through the flow path in a forward direction such that the fluid flows from the inlet through the gas separation device to the outlet; capturing a volume of the gas within the gas separation device, wherein at least a portion of at least one of an inner surface and an outer surface of the housing is translucent so that the volume of the gas can be observed; ceasing delivery of the fluid through the fluid flow path; as well as Fluid is delivered through the fluid flow path in a reverse direction such that the fluid flows from the outlet to the inlet to remove at least a portion of the volume of the gas bubbles from the gas separation device.

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

25. The method of claim 24, wherein: Capturing the volume of gas bubbles includes capturing the volume of gas bubbles within the diffuser portion of the gas separation device.

26. The method of claim 23, wherein: The step of reversing flow occurs once the volume of the bubble approaches a maximum bubble volume defined by approximately 95% of the diffuser portion volume.

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

28. The method of claim 23, wherein: During forward flow through the housing, the gas separation device exhibits a -1 To 0.51mL -1 Air capture efficiency ratio (ATER) between .

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

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

31. The method of claim 23, wherein: The outlet of the gas separation device is fluidly coupled to an inlet of a chromatography device such that the gas separation device and the chromatography device are arranged in series, and wherein the method further comprises delivering a fluid through the outlet of the gas separation device and into the inlet of the chromatography device.

32. A gas separation device comprising: outer shell; an inlet coupled to the outer shell; an inner member disposed within the outer shell and defining a diffuser surface and a core, the diffuser surface having a generally dome-shaped longitudinal profile; a collector disposed below the internal component; a plurality of outlets fluidly coupled to the collector; a fluid flow path defined by the inlet, a partition between the inner component and the outer shell, the collector, and the plurality of outlets; as well as Wherein, the portion of the outer shell which is arranged to be laterally aligned with the diffuser surface and vertically located above the diffuser surface is translucent or transparent.

33. The gas separation device according to claim 32, characterized in that: At least a portion of the core has a circular cross-section.

34. The gas separation device according to claim 32, characterized in that: At least a portion of the core has a rectangular cross-section.

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