Attorney Docket No. 105083-61 END FITTING COMPONENT FOR USE WITH CHROMATOGRAPHY COLUMN CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of and priority to U.S. Provisional Application No. 63/515,862 filed 27 July 2023, the entire disclosure of which is hereby incorporated by reference herein in its entirety for all purposes. INTRODUCTION [0002] The use of chromatography as a laboratory analytical tool is widely known, particularly in applications relating to the pharmaceutical industry and drug development, chemical manufacturing, and clinical toxicology laboratories. During the operation of a chromatography column, a mixture of different chemicals and analytes of interest is separated into is substituent components for detection and quantification. The most important component of a chromatography system is the chromatography column itself. Inside the column, there is a chemically modified sorbent or packing material, known as the stationary phase. A liquid containing the analyte of interest and various buffers is pumped through the column. This is known as the mobile phase. The separation of the various chemical compounds occurs as the analyte is passing through the column, because each chemical compound has a different affinity and interaction for the mobile phase and the stationary phase. [0003] A typical chromatography column contains various system components which are coupled at the inlet and outlet of the system, including frit screens, end caps and tubes wherein the sample of interest is fed through. In order to keep the stationary phase inside the column and to keep undesirable particles in the sample from entering the column, a mechanical filter is placed at the inlet and outlet ends of the column. These filters are commonly known and referred to as frits or frit screens or frit mesh. These frits have to be fine enough to hold the stationary phase, but permeable enough to allow the mobile phase and analyte molecules to pass through the frit. The stationary phase may have particles a few microns diameter, or smaller. Along with retaining the chromatographic stationary media or packing material in the column, the filters or frits also act as a physical filter which keep out particulate contamination that may be present in the sample or the mobile phase, or that are generated by degradation of the particles. In an analytical setting for example, the samples often include blood and plasma which contains
Attorney Docket No. 105083-61 biological components and debris which can clog the frits and reduce the column lifetime. This happens particularly in the central portion of the frit where the sample contacts the frit through the inlet injection tube. At times the sample is not distributed evenly throughout the surface area of the frit and as such, the clogging happens in a concentrated central portion of the frit. This problem is exacerbated during packing of stationary media of the column (in pressurized setting) the screen frit can get pushed into what is known as the four-degree dispersion cone. Once the frit deforms into the dispersion cone, the fluid sample distribution entering the frit screen will be concentrated into a particular area, instead of distributed evenly and uniformly across the entire surface area of the frit. Primarily the fluid entering the column is concentrated onto the center of the frit screen. If the fluid flow exiting the chromatography column is not evenly concentrated, the eluting peak(s) of the sample will be disturbed, resulting in less accurate analyses of the liquid sample. Additionally, the uneven fluid distribution at the frit will cause the center the frit to clog, which results in reduction of the column’s lifetime and the necessity of replacement of the column. This is an expensive and time-consuming issue for laboratory environments which rely on the reliability of a chromatography column for processing their samples in an efficient and timely manner. One solution currently used to ameliorate the issue of debris or particulate clogging in a column’s screen frits is the use a separate guard column which is attached to the column itself. The purpose of the guard column, as the name suggests, is to preempt these issues and be a first screening means for the fluid entering the chromatography column. HPLC guard columns help by removing particulate contaminants and highly absorptive compounds from samples, prior to the sample entering the column itself, and thus they are useful in prolonging column life. Ideally, guard columns should contain the same stationary phase as the analytical column. The drawbacks of relying on guard columns is that they are routinely replaced when they get clogged and are an expensive way to extend the column life. Particularly for users in high throughput applications it is of primary importance to maximize the number of injections on a column, without the added complication of using guard columns, which have to be changed very frequently, and add to labor and material costs.
Attorney Docket No. 105083-61 Therefore, there exists a need in the industry for a means of ensuring the operational integrity of the column is not affected by fluid flow distortions and debris build-up at the inlet frit. There additionally exists a need for a means of ensuring the structural integrity of a frit screen during the packing process of a column, so that deformation of the frit screen into the four-degree cone does not occur. There further remains a need in the art for a means of ensuring even flow distribution across the entire frit screen surface area, so as to avoid clogging issues in a central portion of the frit. Additionally, there exists a need for a solution that can reduce the necessity of using a guard column, which is costly and time consuming to replace for the operator. Lastly, there remains a need for extending the lifetime of a column, by reducing the need for replacing the column due to clogging or flow distributions issues at the inlet frit. SUMMARY The present disclosure relates to end fitting components which are designed to be incorporated with frit assemblies and end caps in a chromatography column. More specifically, presented herein are end fitting components which can be positioned behind an inlet frit assembly and can fit internally within a recess of an inlet end cap. The end fitting component allows for structural support to the frit so that deformation does not occur during packing, and additionally enables equal fluid distribution to a frit during column operation so that the fluid sample passing through the frit contacts the entire surface area, instead of being concentrated only within a central area of the frit. The end fitting components disclosed herein improve the lifetime of a column by reducing clogging issues commonly occurring with frit assemblies, and hence increasing the number of possible runs within a single column. This in turn lowers operating equipment and labor costs related with chromatography equipment.
Attorney Docket No. 105083-61 In one embodiment of the present disclosure, an end fitting component is disclosed which is designed to incorporated within a recess of an end cap of a chromatography column. The end fitting component has a body portion. On a top side of the body portion there is a raised central portion which arises from the body portion of the end fitting. The raised central portion is centrally located within the top side of the body portion and has a circular shape itself. Located and contained within the raised central portion are at least one groove(s) or in some embodiments a plurality of grooves. An aperture is located in the middle of the raised central portion. The aperture is connected to at least one of the at least one groove(s). When a fluid sample is injected into an inlet end cap of a chromatography column, it will pass through the aperture of the end fitting component, and it will then flow and distribute within the grooves of the raised central portion. The fluid will then be distributed through a surface area of a frit which is present right before the entrance bore of a chromatography column. In the embodiment, the at least one groove(s) are presented in a spiral configuration. More specifically, the at least one groove(s) are connected with the aperture and extend outwardly from the aperture in a spiral design. An additional perimeter groove is present. The perimeter groove has a circular shape and lies along the perimeter edge of the raised central portion. The perimeter groove is concentric with the aperture and is not in a spiral configuration. The at least one groove(s) in the spiral configuration are connected with the perimeter groove, meaning that they have end points which terminate at the perimeter groove. In an additional embodiment, the raised central portion contains at least one groove(s), or a plurality of grooves which are in a concentric circular configuration. The at least one groove(s) here are present in a repeated concentric circular configuration, meaning that they have a circular path and are adjacent to each other and encircle each other beginning from the central aperture all the way to the perimeter wall of the raised central portion. The at least one groove(s) in the concentric configuration are connected to each other via at least one or a plurality of through- channels. The through-channels are designed to connect each concentric groove with a pathway for fluid flow. The through-channels in this embodiment extend in a spiral configuration from
Attorney Docket No. 105083-61 the aperture all through the grooves ending in the last perimeter groove. Thus, the through- channels provide a path for fluid to flow from the central aperture through each concentric groove and in this way the fluid entering the end fitting component is distributed evenly through the surface area of the raised central portion, and hence evenly distributed through the surface area of the frit as it moves onwards to the column assembly. A fluid distribution device is also disclosed. The fluid distribution device disclosed comprises a body portion having a bottom side and a top side. A raised central portion arises from the top side of the fluid distribution device. The raised central portion is centrally located within the top side of the body portion. Located and contained within the raised central portion are at least one groove(s). An aperture is located in the middle of the raised central portion. The aperture is connected to at least one of the at least one groove(s). The aperture located within the raised central portion extends through the body portion and is used as a fluid inlet wherein a sample can be injected through the end cap of a chromatography column. The fluid sample which enters the chromatography column, passes through this aperture within the fluid distribution device and is then evenly distributed through a surface area of a frit assembly at tne inlet of the column. Also disclosed is a chromatography device is presented. The chromatography device in one embodiment comprises: - a tubular body having a first opening and a second opening; - a first frit assembly positioned at the first opening and a second frit assembly positioned at the second opening; - an end fitting component recessed within a first end cap, and abutting against the first frit assembly; wherein the end fitting component comprises: - a body portion; - a raised central portion arising from the body portion; - at least one groove(s) contained within the raised central portion; and - an aperture connected with the at least one groove(s).
Attorney Docket No. 105083-61 The tubular body having a first opening and second opening is also referred to as the column portion of the chromatography device. The column will have within the internal diameter, a packing or stationary media. The stationary media is typically comprised of particles, preferably having spherical shape. The particles may differ in size, material, and surface functionality. The chromatography device incorporates a first frit and a second frit. The first frit and second frit are positioned at a first opening (also known as the inlet opening) and at a second opening (also known as an outlet opening) of the column. The first and second frits are typically secured in place through an inlet end cap and an outlet end cap, respectively. The chromatography devices disclosed herein additional incorporates an end fitting component, as described in the various embodiments of this invention. The end fitting component is primarily incorporated at the inlet end of the chromatography device. Although in some embodiments, one such end fitting component can also be incorporated at the outlet end of the column. The end fitting components described herein are incorporated between an inlet end cap and an inlet frit assembly of the chromatography device. Additional advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. The advantages can be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the aspects of the invention, as claimed. Notation and Nomenclature In understanding the scope of the present disclosure, the term “comprising” and its derivatives, as used herein, are intended to be open ended terms that specify the presence of the stated features, elements, components, groups, integers, and/or steps, but do not exclude the presence of other unstated features, elements, components, groups, integers and/or steps. The foregoing also applies to words having similar meanings such as the terms, “including”, “having” and their derivatives. Also, the terms “part,” “section,” “portion,” “member”,
Attorney Docket No. 105083-61 “component” or “element” when used in the singular can have the dual meaning of a single part or a plurality of parts unless otherwise stated. These terms are only used to distinguish one component from another. Thus, for example, a first component discussed above could be termed a second component and vice versa without departing from the teachings of the present disclosure. The term “attached”, “attaching” or “abut”, “abutting, “coupled”, “secured” or “connected”, as used herein, encompasses configurations in which an element is either directly touching another element, or is secured onto another element, or is in close proximity to another element. This definition also applies to words of similar meaning, for example, “joined”, “connected”, “mounted”, “bonded”, “fixed” and their derivatives. Finally, terms of degree such as “substantially”, “about” and “approximately” as used herein mean an amount of deviation of the modified term such that the end result is not significantly changed. The term “about” is used in conjunction with numeric values to include normal variations in measurements as expected by persons skilled in the art, and is understood to have the same meaning as “approximately” and to cover a typical margin of error, such as ±15%, ±10%, ±5%, ±1%, ±0.5%, or even ±0.1% of the stated value. The term “about” also encompasses amounts that differ due to different equilibrium conditions for a composition resulting from a particular initial composition. Whether or not modified by the term “about,” the claims include equivalents to the quantities. It should be noted that, as used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the content clearly dictates otherwise. Thus, for example, reference to a composition containing “a compound” includes having two or more compounds that are either the same or different from each other. It should also be noted that the term “or” is generally employed in its sense including “and/or” unless the content clearly dictates otherwise. As used herein, “and/or” refers to and encompasses any and all possible combinations of one or more of the associated listed items, as well as the lack of combinations when interpreted in the alternative (“or”).
Attorney Docket No. 105083-61 In the interest of brevity and conciseness, any ranges of values set forth in this specification contemplate all values within the range and are to be construed as support for claims reciting any sub-ranges having endpoints which are real number values within the specified range in question. By way of a hypothetical illustrative example, a disclosure in this specification of a range of from 1 to 5 shall be considered to support claims to any of the following ranges: 1-5; 1-4; 1-3; 1-2; 2-5; 2-4; 2-3; 3-5; 3-4; and 4-5. The term “substantially” is utilized herein to represent the inherent degree of uncertainty that can be attributed to any quantitative comparison, value, measurement, or other representation. The term “substantially” is also utilized herein to represent the degree by which a quantitative representation can vary from a stated reference without resulting in a change in the basic function of the subject matter at issue. As used herein, the transitional phrase “consisting essentially of” means that the scope of a claim is to be interpreted to encompass the specified materials or steps recited in the claim and those that do not materially affect the basic and novel characteristic(s) of the claimed invention. Thus, the term “consisting essentially of” when used in a claim of this invention is not intended to be interpreted to be equivalent to “comprising.” The terms “preferred” and “preferably” refer to embodiments that may afford certain benefits, under certain circumstances. However, other embodiments may also be preferred, under the same or other circumstances. Furthermore, the recitation of one or more preferred embodiments does not imply that other embodiments are not useful, and is not intended to exclude other embodiments from the scope of the present disclosure. As used throughout this description, and in the claims, a list of items joined by the term “at least one of” or “one or more of” can mean any combination of the listed terms. For example, the phrase “at least one of X, Y or Z” can mean X; Y; Z; X and Y; X and Z; Y and Z; or X, Y and Z The term “frit” or “frit screen” or “frit mesh” of “frit filter” or “filter” are used interchangeably throughout the disclosure and can refer to the same component. This component
Attorney Docket No. 105083-61 is commonly known in the art as a frit and acts as a filter fluid entering the column and also as a holding means for the stationary packing media contained with a chromatography column. The term “frit” may refer to an inlet or outlet frit, placed at the entrance or at the outlet side of a chromatography column. The term “frit assembly” or “frit screen assembly” of “frit mesh assembly” or “frit filter assembly” refers to the combination of a frit screen or mesh or filter and an the structural component within which the frit is contained, such as an annular ring placed around the frit, hence making up a “frit assembly”. Hence, frit assembly refers to the whole structure, and not just the mesh or screen itself, which is part of the filter component of a frit assembly. While only selected embodiments have been chosen to illustrate the present disclosure, it will be apparent to those skilled in the art from this disclosure that various changes and modifications can be made herein without departing from the scope of the invention as defined in the appended claims. For example, unless specifically stated otherwise, the size, shape, location or orientation of the various components can be changed as needed and/or desired so long as the changes do not substantially affect their intended function. Unless specifically stated otherwise, components that are shown directly connected or contacting each other can have intermediate structures disposed between them so long as the changes do not substantially affect their intended function. The functions of one element can be performed by two, and vice versa unless specifically stated otherwise. The structures and functions of one embodiment can be adopted in another embodiment. It is not necessary for all advantages to be present in a particular embodiment at the same time. Every feature which is unique from the prior art, alone or in combination with other features, also should be considered a separate description of further inventions by the applicant, including the structural and/or functional concepts embodied by such feature(s). Thus, the foregoing descriptions of the embodiments according to the present disclosure are provided for illustration only, and not for the purpose of limiting the invention as defined by the appended claims and their equivalents.
Attorney Docket No. 105083-61 BRIEF DESCRIPTION OF THE DRAWINGS The subject matter which is regarded as the invention is particularly pointed out and distinctly claimed in the claims at the conclusion of the specification. The above and further advantages of this invention may be better understood by referring to the following description in conjunction with the accompanying drawings, in which like numerals indicate like structural elements and features in the various figures. For clarity, not every element may be labeled in every figure. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention. FIG.1A is a perspective view of a front side of an exemplary end fitting component according to one embodiment. FIG.1B is a perspective view of a back side of an exemplary end fitting component according to one embodiment. FIG.2 is a plan view of the central portion of the exemplary end fitting component shown in Fig.1. FIG.3 is an exploded view of an end cap, an end fitting component, a frit assembly and a column according to one embodiment. FIG.4 is an exploded view of an end cap, an end fitting component, a frit assembly and a column according to one embodiment. FIG 5. is a perspective view of an exemplary end fitting component according to one embodiment. FIG.6A is a side view of an end cap of a chromatography column according to one embodiment. FIG.6B is a cross-sectional view of an end cap and an end fitting component residing with an end cap of the present disclosure.
Attorney Docket No. 105083-61 FIG.7 is a plan side view of an end fitting component of the one embodiment of the present disclosure. DETAILED DESCRIPTION A detailed description of the hereinafter described embodiments of the disclosed apparatus and method are presented herein by way of exemplification and not limitation with reference to the Figures. Reference in the specification to “one embodiment” or “an embodiment” means that a particular, feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the teaching. References to a particular embodiment within the specification do not necessarily all refer to the same embodiment. While the present teaching is described in conjunction with various embodiments and examples, it is not intended that the present teaching be limited to such embodiments. On the contrary, the present teaching encompasses various alternatives, modifications and equivalents, as will be appreciated by those of skill in the art. Those of ordinary skill having access to the teaching herein will recognize additional implementations, modifications and embodiments, as well as other fields of use, which are within the scope of the present disclosure as described herein. The present disclosure relates to end fitting components which are designed to be incorporated with frit assemblies and end caps in a chromatography column. More specifically, presented herein are end fitting components which can be positioned behind an inlet frit assembly and can fit internally within an inlet end cap, and allows for structural support to the frit screen so that deformation does not occur during packing, and additionally enables equal fluid distribution a frit during column operation so that the fluid sample passing through the frit contacts the entire surface area, instead of being concentrated only within a central area of the frit. The end fitting components disclosed herein improve the lifetime of a column by reducing clogging issues commonly occurring with frit assemblies, and hence increasing the number of
Attorney Docket No. 105083-61 possible within a single column, thereby lowering operating costs related with chromatography equipment. Referring now to Figs.1A and 1B where an end fitting component 100 according to an embodiment of the present disclosure is shown. Fig.1A shows a topside view and Fig 1B shows the end fitting component from the opposing bottoms side view. The end fitting component 100 has a body portion 70. In one embodiment, the body portion 70 of the end fitting component has a circular shape, although other embodiments are envisioned which are not limited to this shape. The body portion 70 has a bottom side 72 and a top side 74. On the top side 74 of the body portion there is a raised central portion 50 which arises from the body portion 70 of the end fitting. The raised central portion 50 is centrally located within the top side 74 of the body portion and has a circular shape itself. Located and contained within the raised central portion 50 are at least one groove(s) 20 or in some embodiments a plurality of grooves 20. An aperture 40 is located in the middle of the raised central portion 50. The aperture 40 is connected to at least one of the at least one groove(s) 20. The aperture 40 located within the raised central portion 50 extends through the body portion 70. In Fig.1B the void opening 80 which is present on the bottom side 72 of the end fitting component 100 has a conical shape. This opening 80 extends through to the aperture 40 on the top side 74 of the end fitting component 100. The fluid sample which enters the chromatography column, passes through this aperture 40 within the end fitting component 100. The flow of the fluid within through these components and within the column itself will be described in later sections in more detail. In the embodiment shown in Fig.1A, the at least one groove(s) 20 are shown in a spiral configuration. More specifically, the at least one groove(s) 20 are connected with the aperture 40 and extend outwardly from the aperture in a spiral design. An additional perimeter groove 30 is present. The perimeter groove 30 has a circular shape and lies along the perimeter edge of the raised central portion 50. The perimeter groove 30 is concentric with the aperture 40 and is not in a spiral configuration. The at least one groove(s) 20 in the spiral configuration are connected with the perimeter groove 30, meaning that they have end points which terminate at the perimeter groove 30. When fluid to be tested in the chromatography column 300 is injected through an inlet tube (not shown) coupled to an inlet of the end cap 10 of the column, it passes through the end
Attorney Docket No. 105083-61 opening 80 of the end fitting component 100, the component 100 residing internally within a recess of the inlet end cap 10. The fluid passes through the aperture 40 of the end fitting component. The raised central portion 50 of the end fitting component 100, having the aperture 40 centrally therein, is fitted within a frit assembly 200 or abuts against the frit assembly 200. More specifically, the raised central portion 50 fits behind a frit screen 250 of a frit assembly 200. It therefore provides structural support to the frit screen 250, so that during pressurized packing or operation of the column, the frit screen 250 is not deformed backwards towards the end cap 10, as would be common if the end fitting 100 component was not present, and instead a four-degree cone void existed (as is the case in columns presently available in industry). Not only does the raised central portion 50 of end fitting component 100 provide structural support for the frit screen 250 (Fig.3 and 4), the grooves 20 and 30 which reside therein and are connected to the central aperture 40 allow for fluid distribution throughout the raised central portion 50, from the at least one groove(s) 20 and through to the perimeter groove 30. Hence the end fitting component 100 has a dual purpose, one for structural support of the frit 250, so that the frit cannot deform backwards during column packing and operation, and also as a fluid distribution means to the entire available surface of the frit, during sample runs. As fluid enters through the aperture 40, it flows through the at least one groove(s) 20 and thereby also to the perimeter groove 30, and then passes through to the frit screen 250 and then enters the column 300 itself. The fluid has a means of dispersing throughout the raised central portion 50 through the various grooves 20 and 30, and thereby also evenly distributes through the entire surface area of the frit screen 250. By distributing the fluid through the entire surface area of the frit screen 250, the build-up of particulate matter and thereby clogging in only a central portion of the frit screen 250 is eliminated. As fluid is distributed more evenly across the surface area of the frit screen 250, there is less opportunity for clogging of the frit in the central area, which thereby increases the lifetime of the column 300, and reduces downtime and costs associated with having to frequently replace the equipment. Referring now to Fig.2, a closer plan view of the raised central portion 50 can be seen, as it relates to the embodiment depicted in Fig.1A. In this closer view, the at least one groove(s) 20 are shown to extend from and connected to the aperture 40 in the center of the raised central
Attorney Docket No. 105083-61 portion 50. The purpose of having the grooves 20 in connection to the aperture 40 is so that fluid can enter the grooves as it is injected and flowing through the aperture 40. Once it enters the grooves 20 it flows through to the perimeter groove 30 as well. The at least one groove(s) 20 are connected to the perimeter groove 30 in such a way so that fluid can pass from the at least one groove(s) 20 to the perimeter groove 30 without impedance. This allows the fluid to be distributed evenly through the area of the centrally raised portion 50 and equally then through to the surface area of the frit screen 250. The frit screen assembly is fitted around and coupled to the raised central portion 50 and rests on the flat side of the top wall 60 of the end fitting component 100. While in the pictured embodiment shown in Figs 1A and 2, there are three grooves present 20, connecting and terminating with the perimeter groove 30, it is envisioned that the number of grooves can be less or more than what is depicted here. This is merely exemplary and is not considered to be limiting to the scope of the disclosure and the various other embodiments the disclosure enables. For example, there may be two grooves in a spiral configuration, or four grooves, or any other desired number (the number is only limited by the available surface area on the raised central portion). Additionally, although one perimeter groove 30 is currently shown in the embodiment of Figs.1A and 2, more than one perimeter groove can be present. For example, an additional perimeter groove can be placed adjacent and concentric with the depicted perimeter groove 30. Again, both these perimeter grooves would preferably be connected with the at least one grooves in spiral configuration so that fluid can have a path to flow to all the grooves and therefore be able to distribute evenly through the surface area of the raised central portion 50, and thus evenly on the entire surface area of the frit screen 250. Figs.3 and 4 show exploded views of an inlet end cap 10, and end fitting component 100, frit assembly 200 and column 300. The frit assembly 200 has a back side and a front side. The back side is coupled to the end fitting component 100 and on the front side connects to the column inlet 310. A fluid sample would enter this system through an injection tube (not shown) into the end cap 10 and would pass through opening 80 on the bottom side of end fitting component 100 and on through the aperture 40 at the top side of the end fitting component 100. It is understood that the end fitting component 100 resides within a recess in the end cap 10. The fluid sample would then exit the aperture 40 on the top side contained in the raised central portion 50. As the fluid distributes through the grooves 20 and 30 within the raised central
Attorney Docket No. 105083-61 portion 50 of the end fitting component 100 it then passes through the back side of the frit 250, goes through the frit screen 250 and then enters the column itself 300 through an inlet side 310. It then passes through the stationary media contained within the tubular body of column 300 and exists at an outlet 320 of column where typically another outlet frit assembly and outlet end cap are present (not shown). As can be seen in Figs.3 and 4 the frit assembly 200 has a circular shape and has an exposed frit screen or mesh 250 with a diameter commensurate with the inlet opening 310 of the column 300 itself. The frit 250 is surrounded by an annular ring 230. On the back side of the frit assembly 200 the frit itself is indented within the annular ring 230 so that a recessed center 270 is present, as can be seen in Fig.4. The size of this recessed center 270 of the frit assembly 200 corresponds to the size of the raised central portion 50 on the end fitting component 100. More specifically, the diameter of the raised central portion 50 has to be similar to the diameter of the recessed center area 270 of the back side of the frit assembly where the frit screen 250 is exposed. The diameter of the raised central portion 50 is just slightly smaller so that it fits within this recess 270, but only to the necessity to create a very tight-fitting seal. The connection between these two pieces is important in that the seal between the two components has to be very tight fitting so as to ensure that that when fluid passes from the aperture 40 in the end fitting component and on through the frit screen 250, there is no fluid or sample loss and all the fluid passes through to the available surface area of the frit screen 250 or mesh and enters the corresponding inlet 310 opening of the chromatography column 300. The annular ring component 230 of the frit assembly 200, on its back side will rest on the flat top side wall 60 of the end fitting component 100. Whereas the front side of the frit assembly 200, the annular ring 230 will align with the inlet 310 of the column itself. Once the inlet end cap 10 is threaded onto the column 300 itself, it will create a tight-fitting seal between the end fitting component 100 (which resides within the end cap 10) the frit assembly 200 and the column itself 300. On the outlet end of the column 320 there is an outlet end cap and an outlet frit assembly (not pictured). Because the sample particulate clogging issues are present at the inlet end 310 of a column 300, the end fitting components of the present disclosure are only necessary to be incorporated at an inlet end of a chromatography column, and there is no real necessity for such a
Attorney Docket No. 105083-61 component at the outlet end. Nevertheless, there can be an end fitting component 100 present within an outlet end cap as well, perhaps for structural support (not shown). Moving now to another embodiment of the present disclosure, varying configurations are envisioned for the placement of the grooves within the raised central portion of the end fitting component, such as the configuration shown in Fig.5 In this embodiment, the raised central portion 50 contains at least one groove(s) 20, or a plurality of grooves which are in a concentric circular configuration. This differs from the embodiment discussed previously which had the plurality of grooves in a spiral configuration. The at least one groove(s) 20 here are present in a concentric circular configuration, meaning that they have a circular path and are adjacent to each other and encircle each other beginning from the central aperture 40 all the way to the perimeter wall of the raised central portion 50. The at least one groove(s) 20 in the concentric configuration are connected to each other via at least one or a plurality of through-channels 25. The through- channels 25 are designed to connect each concentric groove 20 with a pathway for fluid flow. The through-channels 25 as shown in this embodiment extend in a spiral configuration from the aperture all through the grooves 20 ending in the last perimeter groove 30. Thus, the through- channels 25 provide a path for fluid to flow from the central aperture 40 through each concentric groove 20 and in this way the fluid entering the end fitting component 100 is distributed evenly through the surface area of the raised central portion 50, and hence evenly distributed through the surface area of the frit 250 as it moves onwards to the column 300. Although two through- channels 25 are shown in the present depiction in Fig.5, it is envisioned that less or more through-channels can be incorporated in the manufacture of end fitting component of the present disclosure. The through-channels 25 shown in this embodiment have a spiral configuration, however, the present disclosure is not limited to this configuration. In other embodiments, through- channels 25 can be present and have a straight line configuration, wherein they radiate outwardly from the aperture 40 through the grooves 20 and terminate at the perimeter groove 30, in a straight line, not in a curved spiral path. Other types of paths are envisioned as well, such as zig- zag or curved. The spiral configuration shown in Fig.5 is therefore only meant to be exemplary and does not limit the disclosure in any way with respect to the configuration of the through- channels.
Attorney Docket No. 105083-61 Fig.6A shows a side view of an end cap 10 to be used with the chromatography columns described herein. Fig.6B is a cross-section view of end cap 10, and depicts how the end fitting components 100 and frit assembly 200 of the present disclosure reside within a recess of the end cap 10. The end cap has a top side 5 and a bottom side 2. Both these sides can have threaded internal structure so that they can attach on to the various components of the chromatography column systems described herein. As can be seen in Fig.6B, an end fitting component 100 and frit assembly 200 are coupled together and reside within a recess of the end cap 10. Internal channel 3 of end cap 10 is used as an inlet for the injection of fluid sample. Various tubing and injection components can be coupled to internal channel 3 (not shown). Fluid samples would be injected from bottom side 2 of the end cap and pass through the bottom side of the end cap fitting 100, it would exit through aperture 40 then pass onto frit assembly 200 and then onwards to inlet 310 of the column 300. Moving now to Fig.7, the end fitting component 100 described herein in the various embodiments is designed to be applicable in a variety of sizes, depending on the type and size of chromatography column it will be incorporated with. According to one embodiment presented herein, the outer diameter of the body portion 70 of the end component 100, defined by D1, is the same size or substantially the same size as the diameter of a frit assembly 200 with which the end fitting component will correspond. The diameter of the frit assembly 200 itself is the same or substantially the same as the diameter of an inlet portion 310 of a column 300 within which the frit will be used. Depending on the internal diameter and size of the column with which the frit assembly and end fitting component will be used with, the size and overall dimensions of both these components will vary. For example for a column having a length of 50 mm, and an internal diameter of 2.1 mm (50 X 2.1 mm column), the diameter of a frit assembly will be in the range of about 5.4 -5.6 mm, or about 5.5 mm and a diameter, D1 of an end fitting component will also be in the range of 5.4-5.6 mm, or about 5.5 mm. For larger or smaller sized columns, D1 will vary accordingly, and can be in the range of 1.0 mm to 10 mm, or 2 to 9 mm, or 3 to 8 mm, or 4 to 7 mm, or 5 to 6 mm. As can be seen in Fig.7, the diameter D2 of the raised central portion will correspond with a substantially similar diameter of a recessed center portion 270 on the back side of the frit assembly 200 (see Figs 3 and 4). This ensures that the raised center portion diameter D2 is appropriately sized so that a tight-fitting connection can be made between
Attorney Docket No. 105083-61 the raised central portion 50 and the recessed center portion 270 of the backside of the frit assembly 200. For a 2.1 mm internal diameter (ID) column, the diameter D2 can measure about 2.1 mm. For a variety of different sizes of columns, the ID can range between about 1.0 mm to about 7.8 mm. Therefore, D2 can also range between about 1.0 mm to about 7.8 mm. Similarly, the height C, which corresponds to the height measurement of the perimeter wall of the raised central portion 50, will correspond with a depth measurement of the recessed center portion 270 of the backside of the frit assembly 200. Height C for a 2.1 mm ID column, measures about 0.8- 1.2 mm, or about 1.0 mm. For larger or smaller columns, the height measurement of C will increase or decrease accordingly depending on the size of the frit assembly. In embodiments, C can range from 0.5 mm to 4.0 mm, or 1 mm to 3 mm, or 1.5 mm to 2.5 mm, or any value between. These measurements are substantially similar, because once the two parts are connected or coupled together, the annular ring 230 will be in substantially touching connection to the flat wall on the top side of the end fitting component 100. For a 2.1 mm ID column, the size of length A can be for example about 4.0 mm - 5.0 mm, or about 4.5 mm. In other embodiments, A can range from 1.0 mm to 12 mm, or 2 -11 mm, or 3-10 mm, or 4-9 mm, or 5-8 mm, or 6-7 mm, or any value between. The length dimension of B1 corresponding to a distance from the perimeter of the raised central portion 50 to an outer perimeter of the body portion 70 of the end fitting component will similarly be the same dimension as that of an annular ring 230 on the frit assembly 200. For example, for a 2.1 ID column, the length of B1 measures about a 1.5-1.9 mm, or about 1.7 mm. For larger or small ID columns, this length B1 will be smaller or larger accordingly. In other embodiments, B1 can range from 0.5 mm to 12 mm, or 1-11 mm, or 2-10 mm, or 3-9 mm, or 4-8 mm, or 5-7 mm, or any number in between. As previously described the annular ring 230 of the frit assembly 200 rests on the top side flat wall 60 of the end fitting component, around the raised central portion 50. The length or height A, of the body portion 50 will correspond to the available space and recess within an end cap 10 within which the end fitting component 100 will reside, once the end cap 10 is threaded onto and connected with the end portions of the column 300. The value of A will of course depend on the size and the design of the end cap being used on a particular sized column. The measurements of any of the dimensions, include A, B1, C, D1 and D2 can be altered and modified within certain limits, so that they will accommodate the size
Attorney Docket No. 105083-61 of the column 300, the frit assembly 200 and the end cap 10 within which they reside. The limitation on these measurements is only with respect to the components with which they will communicate and be coupled with within a chromatography system. In some embodiments, it is envisioned that the end fitting component 100 will be incorporated in columns of various internal diameters, including internal diameter of 2.1 mm, 3.0 mm and 4.6 mm columns, or any known standard column diameters typically utilized in industry and known to those in the art. The measurements of parameters A, B1, C, D1 and D2 of the end fittings incorporated in columns having internal diameters of 3.0 mm and 4.6 mm, will differ respectively from the disclosed parameters listed above for the 2.1 mm internal diameter columns. Parameters A, B1, C, D1 and D2 will be larger for said columns, when compared to the 2.1 mm columns. For example, parameter D2 will have to correspond to the internal diameter of a 3.0 mm ID column, with D2 measuring about 3.0 mm, similarly with a 4.6 mm ID, the diameter D2 will be about 4.6 mm. The other parameters will also vary with increasing size, if used in larger internal diameter columns. The embodiments disclosed herein are to be used for chromatography columns of varying size and internal diameter. In embodiments, the internal diameter of the columns (i.e. of the tubular body) is about 1.0 mm to 7.8 mm. In the embodiment shown in Fig.1A, the at least one groove(s) 20 and the perimeter groove 30 have substantially similar or equal dimensions in terms of depth and width. These dimensions can alter from each other about 10-20% without imparting any practical differences in terms of the operation and functionality of the grooves. In the embodiment shown in Fig.5, where the at least one grooves 20 have a concentric configuration and wherein through-channels 25 are present, the dimensions of the through-channels 25 and that of the at least one groove(s) 20 are substantially similar or equal with respect to width and depth. In some embodiments, the width of the through-channels 25 and that of the at least one groove(s) 20 are substantially equal. In other embodiments, the width and or depth of the through-channels 25 is smaller or larger than that of the at least one groove(s) 20 by a factor of about 5-30 %. The end fitting components disclosed herein can be manufactured from a variety of materials, including metallic, ceramic, polymeric or elastomeric materials. In a preferred embodiment, the end cap fitting component is comprised of a metallic material, including
Attorney Docket No. 105083-61 stainless steel, aluminum, titanium, MP35N, or Inconel. In other embodiments, the end cap fitting component can be comprised of a polymeric material, including a thermoplastic polymer such as polyether ether ketone (PEEK). In additional embodiments, the end cap fitting component can be manufactured from a glass, or silica material, a ceramic material, such as including but not limited to aluminum oxide. According to various embodiments, any of the exemplary end fitting component described herein can be produced through a micro-machining process, according to various techniques. For example, micro-machining can be used to form the at least one groove(s), the perimeter groove, and the through-channels of the various described embodiments. For example, micro-machining techniques such as etching or laser milling can be used. Etching techniques include deep reactive ion etching (RIE), dry etching, wet etching, plasma etching, electro-chemical etching, gas phase etching, and the like. Additionally, lithography techniques as known in the art can be used as a masking step to define the components (e.g., holes, cavities, channels, etc.) of the exemplary end fitting components disclosed herein. Etching techniques can then be used to form the components. As discussed previously the embodiments disclosed herein for end fitting components have a dual purpose, for providing structural support to frits, frit mesh or screens during column packing and operation and further to ensure even fluid distribution of the sample so that the sample is distributed throughout the entire available surface of the frit. As such, a the end fitting components disclosed here are also useful as fluid distribution devices. Hence, disclosed are fluid distribution devices for use with frits or frit assemblies in a chromatography column. The fluid distribution devices of the present disclosure have a body portion 70. In one embodiment, the body portion 70 of the fluid distribution device has a circular shape, although other embodiments are envisioned which are not limited to this shape. The body portion has a bottom side 74 and a top side 72. On the top side of the body portion there is a raised central portion 50 which arises from the body portion of the fluid distribution device 100, and specifically from the top side of the body portion 70. The raised central portion 50 is centrally located within the top side of the body portion and has a circular shape itself. Located and contained within the raised central portion are at least one groove(s) 20 or in some embodiments a plurality of grooves. An aperture 40 is located in the middle of the raised central portion 50. The aperture 40 is connected
Attorney Docket No. 105083-61 to at least one of the at least one groove(s) 20. The fluid sample which enters the chromatography column, passes through this aperture 40 within the fluid distribution device. In a fluid distribution device shown in an embodiment presented in Fig.1A, the at least one groove(s) 20 are shown in a spiral configuration. More specifically, the at least one groove(s) are connected with the aperture 40 and extend outwardly from the aperture in a spiral design. An additional perimeter groove 30 is present. The perimeter groove 30 has a circular shape and lies along the perimeter edge of the raised central portion 50. The perimeter groove 30 is concentric with the aperture 40 and is not in a spiral configuration. The at least one groove(s) 20 in the spiral configuration are connected with the perimeter groove, meaning that they have end points which terminate at the perimeter groove 30. When fluid to be tested in the chromatography column is injected through an inlet tube (not shown) coupled to an inlet end cap of the column, it passes through the fluid distribution device 100 internally within a channel 3 of the inlet end cap 10. The fluid passes through the aperture 40 of the fluid distribution device. The raised central portion of the fluid distribution device 100, having the aperture 40 centrally therein, is fitted within a frit assembly 200 or abuts against the frit assembly. More specifically, the raised central portion 50 fits behind a frit screen 250 of a first assembly 200. The fluid distribution device 100 has the at least one groove(s) 20 connected to the central aperture 40 and this allows for fluid distribution throughout the raised central portion 50, from the at least one groove(s) and through to the perimeter groove 30. As fluid enters through the aperture 40, it flows through the at least one groove(s) 20 and thereby also to the perimeter groove 30, and then passes through to the frit screen 250 and then enters the column itself 300. Because the fluid has a means of dispersing throughout the raised central portion 50 through the various grooves 20 and 30, it also now evenly distributes through the entire surface area of the frit screen 250. By distributing the fluid through the entire surface area of the frit screen 250, the build-up of particulate matter and thereby clogging in only a central portion of the frit screen 250 is eliminated. As fluid is distributed more evenly across the surface area of the frit screen 250, there is less opportunity for clogging of the frit in the central area, which thereby increases the lifetime of the column, and reduces downtime and costs associated with having to frequently replace the equipment.
Attorney Docket No. 105083-61 The fluid distribution devices disclosed herein can have a configuration of various designs with respect to the at least one groove(s) 20 and the perimeter grooves 30. All aforementioned designs which were disclosed with respect to embodiments of an end fitting component above, also apply to the embodiments disclosing a fluid distribution device. All the foregoing discussions pertaining to dimensions, designs, materials, production and machining means are also to be incorporated herein for the embodiments of the fluid distribution device (and are not replicated here for brevity). The embodiments of the groove(s) 20 within a raised central portion 50 for the fluid distribution devices of the present disclosure will encompass designs previously discussed above, including the spiral configurations and concentric circle configurations having the through-channels 25, and all discussed embodiments shown in Figs 1- 7. Also disclosed is a chromatography device. The chromatography device disclosed herein comprises but is not limited to the following components: - a tubular body 300 having a first opening 310 and a second opening 320; - a first frit assembly 200 positioned at the first opening and a second frit (not shown) assembly positioned at the second opening 320; - an end fitting component 100 recessed within a first end cap 10, and abutting against the first frit assembly 200; wherein the end fitting component comprises: - a body portion 70; - a raised central portion 50 arising from the body portion; - at least one groove(s) 20 contained within the raised central portion; and - an aperture 40 connected with the at least one groove(s) 20. The tubular body having a first opening and second opening is also referred to as the column portion 300 of the chromatography device and is depicted on Figs.3 and 4. The column will have within the internal diameter, a packing or stationary media (not shown). The stationary media is typically comprised of particles, preferably having spherical shape. The particles may differ in size, material, and surface functionality. The particles can have average diameters of about 2-8 microns, or more specifically 3-5 microns. The chromatography device incorporates a
Attorney Docket No. 105083-61 first frit and a second frit (not shown). The first frit and second frit are positioned a first opening (also known as the inlet opening) and at a second opening (also known as an outlet opening) of the column. The first and second frits are typically secured in place through a inlet end cap and an outlet end cap, respectively. The chromatography devices disclosed herein additional incorporates an end fitting component, as described in the various embodiments of this invention. The end fitting component is primarily incorporated at the inlet end of the chromatography device and is not necessary to be included at the outlet end. Although in some embodiments one such end fitting component can also be incorporated at the outlet end of the column. The end fitting components described herein are incorporated between an inlet end cap and an inlet frit assembly of the chromatography device. Figs 3 and 4 show the alignment and configuration of the placement of the end fitting components within the chromatography devices disclosed herein. All previously discussed embodiments with respect to the end fitting components and fluid distribution devices outlined in the disclosure are incorporated herein with respect to the chromatography devices of this invention. Although these inventions have been disclosed in the context of certain preferred embodiments and examples, it will be understood by those skilled in the art that the present disclosures extend beyond the specifically disclosed embodiments to other alternative embodiments and/or uses of the inventions and obvious, modifications and equivalents thereof. In addition, while several variations of the inventions have been shown and described in detail, other modifications, which are within the scope of these inventions, will be readily apparent to those of skill in the art based upon this disclosure. It is also contemplated that various combination or sub-combinations of the specific features and aspects of the embodiments may be made and still fall within the scope of the inventions. It should be understood that various features and aspects of the disclosed embodiments can be combined with or substituted for one another in order to form varying modes of the disclosed inventions. Thus, it is intended that the scope of at least some of the present disclosures herein disclosed should not be limited by the particular disclosed embodiments described above. The following numbered clauses define further example aspects and features of the present disclosure:
Attorney Docket No. 105083-61 1. An end fitting component for use in a chromatography column, said component comprising: a body portion; a raised central portion arising from the body portion; at least one groove(s) contained within the raised central portion; and an aperture connected with the at least one groove(s). 2. The end fitting component of clause 1, wherein the raised central portion abuts against a frit assembly within the chromatography column. 3. The end fitting component of clause 1, wherein the at least one groove(s) comprise groove(s) in a spiral configuration. 4. The end fitting component of clause 3, wherein the at least one groove(s) further comprise a perimeter groove. 5. The end fitting component of clause 1, wherein the at least one groove(s) are in a concentric configuration. 6. The end fitting component of clause 5, wherein the at least one groove(s) in concentric configuration are connected via a plurality of through-channels. 7. The end fitting component of clause 5, wherein the at least one groove(s) in concentric configuration are connected to the aperture via a plurality of through-channels. 8. The end fitting component of clauses 6 or 7, wherein the plurality of through-channels extend from the aperture to a perimeter wall of the raised central portion in a spiral configuration.
Attorney Docket No. 105083-61 9. The end fitting component of clause 1, wherein the raised central portion has a height of about 0.5 mm to 4.0 mm. 10. The end fitting component of clause 1, wherein the raised central portion has a diameter of about 1.0 mm to 7.8 mm. 11. The end fitting component of clause 1, further comprising a perimeter wall which aligns with a recessed center portion of a frit assembly in the chromatography column. 12. The end fitting component of clause 1, wherein the raised central portion has a diameter substantially equal to the diameter of the recessed center portion of the frit assembly. 13. The end fitting component of clause 1, wherein a fluid enters through the aperture and is distributed through the at least one groove(s) connected to the aperture. 14. The end fitting component of clause 13, wherein the fluid that is distributed through the at least one groove(s) is further distributed throughout the surface area of a frit as it enters the chromatography column. 15. The end fitting component of clause 1, wherein the end fitting component is configured to fit inside a recess of an end cap of a chromatography column. 16. The end fitting component of clause 1, wherein the end fitting component is comprised of metallic, polymeric, elastomeric, or ceramic material. 17. The end fitting component of clause 16, wherein the end fitting component is comprised of stainless steel, aluminum, titanium, MP35N, Inconel, polyether ether ketone (PEEK), silica, or aluminum oxide.
Attorney Docket No. 105083-61 18. A fluid distribution device for use in a chromatography column, said fluid distribution device comprising: a body portion; a raised central portion arising from the body portion; at least one groove(s) contained within the raised central portion; and an aperture connected with the at least one groove(s). 19. The fluid distribution device of clause 18, wherein the raised central portion abuts against a frit assembly within the chromatography column. 20. The fluid distribution device of clause 18, wherein the at least one groove(s) comprise groove(s) in a spiral configuration. 21. The fluid distribution device of clause 18, wherein the at least one groove(s) further comprise a perimeter groove. 22. The fluid distribution device of clause 1, wherein the at least one groove(s) are in a concentric circular configuration. 23. The fluid distribution device of clause 22, wherein the at least one groove(s) in concentric configuration are connected via a plurality of through-channels. 24. The fluid distribution device of clause 22, wherein the at least one groove(s) in concentric configuration are connected to the aperture via a plurality of through-channels. 25. The fluid distribution device of clauses 23 or 24, wherein the plurality of through- channels extend from the aperture to a perimeter wall of the raised central portion in a spiral configuration.
Attorney Docket No. 105083-61 26. The fluid distribution device of clause 18, wherein the raised central portion has a height of about 0.5 mm to 4.0 mm. 27. The fluid distribution device of clause 18, wherein the raised central portion has a diameter of about 1.0 mm to 7.8 mm. 28. The fluid distribution device of clause 18, further comprising a perimeter wall which aligns with a recessed center portion of a frit assembly in the chromatography column. 29. The fluid distribution device of clause 28, wherein the raised central portion has a diameter substantially equal to the diameter of the recessed center portion of the frit assembly. 30. The fluid distribution device of clause 18, wherein a fluid enters through the aperture and is distributed through the at least one groove(s) connected to the aperture. 31. The fluid distribution device of clause 30, wherein the fluid that is distributed through the at least one groove(s) is further distributed throughout the surface area of a frit as it enters the chromatography column. 32. The fluid distribution device of clause 18, wherein the end fitting component is configured to fit inside a recess of an end cap of a chromatography column. 33. The fluid distribution device of clause 18, wherein the end fitting component is comprised of metallic, polymeric, elastomeric, or ceramic material. 34. The fluid distribution device of clause 33, wherein the end fitting component is comprised of stainless steel, aluminum, titanium, MP35N, Inconel, polyether ether ketone (PEEK), silica, or aluminum oxide.
Attorney Docket No. 105083-61 35. A chromatography device comprising: - a tubular body having a first opening and a second opening; - a first frit assembly positioned at the first opening and a second frit assembly positioned at the second opening; and - an end fitting component; wherein the first end fitting component comprises: - a body portion; - a raised central portion arising from the body portion; - at least one groove(s) contained within the raised central portion; and - an aperture connected with the at least one groove(s). 36. The chromatography device of clause 35, wherein the raised central portion abuts against a frit assembly within the chromatography column. 37. The chromatography device of clause 35, wherein the at least one groove(s) comprise groove(s) in a spiral configuration. 38. The chromatography device of clause 37, wherein the at least one groove(s) further comprise a perimeter groove. 39. The chromatography device of clause 35, wherein the at least one groove(s) are in a concentric circular configuration. 40. The chromatography device of clause 39, wherein the at least one groove(s) in concentric configuration are connected via a plurality of through-channels. 41. The chromatography device of clause 39, wherein the at least one groove(s) in concentric configuration are connected to the aperture via a plurality of through-channels.
Attorney Docket No. 105083-61 42. The chromatography device of clauses 40 or 41, wherein the plurality of through- channels extend from the aperture to a perimeter wall of the raised central portion in a spiral configuration. 43. The chromatography device of clause 35, wherein the raised central portion has a height of about 0.5 mm to 4.0 mm. 44. The chromatography device of clause 35, wherein the raised central portion has a diameter of about 1.0 mm to 7.8 mm. 45. The chromatography device of clause 35, further comprising a perimeter wall which aligns with a recessed center portion of a frit assembly in the chromatography column. 46. The chromatography device of clause 45, wherein the raised central portion has a diameter substantially equal to the diameter of the recessed center portion of the frit assembly. 47. The chromatography device of clause 35, wherein a fluid enters through the aperture and is distributed through the at least one groove(s) connected to the aperture. 48. The chromatography device of clause 47, wherein the fluid that is distributed through the at least one groove(s) is further distributed throughout the surface area of a frit as it enters the chromatography column. 49. The chromatography device of clause 35, wherein the end fitting component is configured to fit inside a recess of an end cap of a chromatography column. 50. The chromatography device of clause 35, wherein the end fitting component is comprised of metallic, polymeric, elastomeric, or ceramic material.
Attorney Docket No. 105083-61 51. The chromatography device of clause 50, wherein the end fitting component is comprised of stainless steel, aluminum, titanium, MP35N, Inconel, polyether ether ketone (PEEK), silica, or aluminum oxide. 52. The chromatography device of clause 35, wherein the tubular body has an internal diameter of about 1.0 mm to 7.8 mm.