Patent Description:
Chromatography frequently includes flowing a fluid through a medium in a tube for separation of a sample into its component parts. The medium can comprise bed of small beads. For some devices, a device is required to retain the medium in the tube against gravity forces and/or the force imposed upon the medium by the fluid flowing through the medium. It is desirable that the devices that retain the medium not interact with the medium and/or the sample components and that it be designed to sufficiently support the medium to avoid damage to the device the medium or other parts associated with the chromatography system. A plug for a chromatographic cartridge is disclosed in <CIT>.

Disclosed is a chromatography plug, the chromatography plug comprising: a body, the body comprising: a first surface; a second surface opposing the first surface; a passage through the body extending from an opening in the first surface to an opening in the second surface; and a circumferential surface extending from the first surface to the second surface; a plurality of ridges, located on the first surface, wherein each of the plurality of ridges having a first end and an opposed second end, and the first end of each of the plurality of ridges being closer to one another than the second ends of each of the plurality of ridges; and a bridge located between the first ends, the bridge extending into the body.

Disclosed is a chromatography plug, the chromatography plug comprising: a body, the body comprising: a first surface; a second surface opposing the first surface; a passage through the body extending from an opening in the first surface to an opening in the second surface; and a circumferential surface extending from the first surface to the second surface; a plurality of ridges, located on the first surface, wherein each of the plurality of ridges having a first end and an opposed second end, and the first end of each of the plurality of ridges being closer to one another than the second ends of each of the plurality of ridges; and a bridge located between the first ends, the bridge extending into the body, wherein the first surface comprises: a peripheral rim located at a periphery of the first surface, the first surface defining a central opening with the peripheral rim at a periphery of the central opening, the peripheral rim having a top face directed away from the second face; and a sloped face extending from the peripheral rim to the opening in the first surface, wherein the sloped face forms an obtuse angle with the peripheral rim; wherein each of the plurality of ridges is recessed from the top face, each of the plurality of ridges having a top surface distal the first surface and the bridge having a top surface; the bridge extending into the body at the opening in the first surface and supported by an interior surface of the passage and the bridge having a top surface external to the body and facing away from the first surface.

Disclosed is a chromatography column cartridge comprising: a tube having a first end and a second end opposite the first end; a chromatography plug, wherein the chromatography plug comprises: a body, the body comprising: a first surface; a second surface opposing the first surface; a passage through the body extending from an opening in the first surface to an opening in the second surface; and a circumferential surface extending from the first surface to the second surface; a plurality of ridges, located on the first surface, wherein each of the plurality of ridges having a first end and an opposed second end, and the first end of each of the plurality of ridges being closer to one another than the second ends of each of the plurality of ridges; and a bridge located between the first ends, the bridge extending into the body, wherein the first surface comprises: a peripheral rim located at a periphery of the first surface, the first surface defining a central opening with the peripheral rim at a periphery of the central opening, the peripheral rim having a top face directed away from the second face; and a sloped face extending from the peripheral rim to the opening in the first surface, wherein the sloped face forms an obtuse angle with the peripheral rim; wherein each of the plurality of ridges is recessed from the top face, each of the plurality of ridges having a top surface distal the first surface and the bridge having a top surface; the bridge extending into the body at the opening in the first surface and supported by an interior surface of the passage and the bridge having a top surface external to the body and facing away from the first surface; wherein the chromatography plug is located in the first end with the circumferential surface in sealing communication with the tube; and a porous partition located in the central opening and contacting the peripheral rim and supported by the top surfaces of the plurality of ridges and the top surface of the bridge.

In the following description, numerous specific details are set forth to clearly describe various specific embodiments disclosed herein. One skilled in the art, however, will understand that the presently claimed invention may be practiced without all of the specific details discussed below. In other instances, well known features have not been described so as not to obscure the invention.

In some embodiments of a chromatography system, a chromatography column can comprise a body with a medium (or stationary phase) located within. A plug can be provided in one or both ends to retain the medium within the column, where the plug provides a flow path from a first end, such as end proximate the medium to a second end distal the medium. In some embodiments, the flow can be from the end distal the medium to the end proximal the medium.

<FIG> shows an embodiment of a chromatography column <NUM> comprising a tube <NUM>, medium <NUM>, a first plug <NUM> and a second plug <NUM>. As shown in <FIG>, the fluid (or mobile phase) can travel from the first end <NUM>, through the first plug <NUM>, through a first partition <NUM>, through the medium <NUM>, through the second partition <NUM>, through the second plug <NUM>, and out the second end <NUM>.

<FIG> shows an embodiment of a plug <NUM>. Plug <NUM> can comprise a body <NUM> configured to fit into and seal the tube of a chromatography tube or a fitting of a chromatography tube against leaks. The body <NUM> can have a first surface <NUM>, a second surface <NUM> and a circumferential surface <NUM> extending between the first surface <NUM> and the second surface <NUM>. As shown in <FIG>, first surface <NUM> can include an optional peripheral rim <NUM> located at a periphery of the first surface <NUM>. In some embodiments, a portion of first surface <NUM> can have a sloped shape forming a sloped face <NUM> which can be placed at an obtuse angle <NUM> with optional peripheral rim <NUM> and/or can be placed at an acute angle <NUM> with circumferential surface <NUM> and can direct flow of fluid passing through the chromatography column to the opening <NUM> in the first surface <NUM> and into passage <NUM>.

The first surface <NUM> can have a plurality of ridges <NUM> extending from the first surface <NUM>. Each of the plurality of ridges having a respective first end <NUM> and a second end <NUM>. As shown in <FIG>, each of the plurality of ridges can extend from the first surface <NUM> in a direction away from the second surface <NUM> with a top surface <NUM> distal the first surface, with the second end <NUM> proximate or contacting a peripheral rim <NUM> located at a periphery of the body <NUM>. In some embodiments, the ridges can have a graduated thickness which is thin at the second end <NUM> and thick at the first end <NUM>, and the graduated thickness can follow the sloped shape of the first surface <NUM> such that the top surface <NUM> of the ridges <NUM> form a substantially level surface that is substantially perpendicular to the circumferential surface <NUM>.

In some embodiments, two ridges <NUM> can be present, and in other embodiments a greater number of ridges can be present, such as <NUM>, <NUM>, <NUM>, <NUM> or more. In some embodiments, the ridges can be positioned around an opening <NUM> in the first surface <NUM>. In some embodiments, the opening <NUM> in the first surface <NUM> can be located at the center of the first surface <NUM>, while in other embodiments, the opening <NUM> in the first surface <NUM> can be offset from the center of the first surface <NUM>.

In some embodiments, the plurality of ridges <NUM> can be arranged in a spoke and hub arrangement with the opening <NUM> in the first surface <NUM>. In some embodiments, the opening <NUM> in the first surface <NUM> can be centered within the plurality of ridges <NUM>, while in some embodiments, the opening <NUM> in the first surface <NUM> can be located at a location that off-center from the plurality of ridges <NUM>.

In some such embodiments, each of the plurality of ridges <NUM> can have a first end <NUM> and a second end <NUM> where the first end <NUM> is located proximate the opening <NUM> in the first surface <NUM> and the second end <NUM> is located distal the opening <NUM> in the first surface <NUM>. In some embodiments, each of the first ends <NUM> can be located equal distance from the opening <NUM> in the first surface <NUM>, and in some embodiments, one or more of the first ends <NUM> can located a different distance from the opening <NUM> in the first surface <NUM> than the other first ends <NUM>. In some embodiments, each of the plurality of ridges <NUM> can be evenly distributed around the opening <NUM> in the first surface <NUM>, such as where two ridges are located <NUM>° apart from one another, or where each of the three ridges are located <NUM>° from the nearest ridge <NUM>, or where each of the four ridges are located <NUM>° from the nearest ridge <NUM>. To generalize this arrangement, each of n ridges <NUM> can be located <NUM>°/n apart from the nearest ridge <NUM>. In some embodiments, the ridges <NUM> can be both evenly distributed around the opening <NUM> in the first surface <NUM> and have each of the first ends <NUM> located an equal distance from the opening <NUM> in the first surface <NUM>.

As is shown in <FIG>, a bridge <NUM> is positioned between the first ends <NUM> of ridges <NUM>. Bridge <NUM> can be connected or disconnected from the ridges <NUM>, such as being connected at first end <NUM>.

<FIG> is a top perspective view of an embodiment of a plug <NUM> with the ridges <NUM> and bridge <NUM> arranged in a hub and spoke pattern. In this embodiment, the plug can be viewed as extending upward from the first surface <NUM> or as extending down into the passage <NUM>, with the top surface <NUM> of the bridge <NUM> being level or approximately level with the top surface <NUM> of the ridges <NUM>. Openings <NUM> in first surface <NUM> are adjacent to the bridge <NUM> and the first ends <NUM> of the ridges <NUM>. The first surface <NUM> can have a portion that slopes from the peripheral rim <NUM> to the bridge <NUM> and/or the openings <NUM> in the first surface <NUM>.

A bridge <NUM> is positioned between the first ends <NUM> of the plurality of ridges <NUM> to assist in supporting a partition <NUM> located on or above the plurality of ridges <NUM>. The bridge <NUM> has a top surface <NUM> external to the body <NUM> and facing away from the first surface <NUM>, the top surface <NUM> of the bridge <NUM> can be even or approximately even with a top surface <NUM> of one or more or all of the plurality of ridges <NUM>. One embodiment of a bridge <NUM> positioned between the first ends <NUM> of the plurality of ridges <NUM> and in a position to support a partition <NUM> is shown in <FIG>. In some embodiments, the bridge <NUM> can contact or connect to the ridges <NUM>, such as the first ends <NUM> of the ridges <NUM> as shown in <FIG>. In some embodiments, there can be a gap between the bridge <NUM> and the first end <NUM> of one or more or all of the ridges <NUM>. The bridge <NUM> extends over at least a portion of opening <NUM> in first surface <NUM> and extends into opening <NUM>.

The bridge <NUM> can be circular or some other shape, such as a shape comprising lobes or extensions directed toward one, multiple or all of the plurality of ridges <NUM>, such as shown in <FIG>. In some embodiments, the bridge can be a series of segments that extend from at least a portion of the plurality of ridges <NUM> over the opening <NUM> in the first surface <NUM> and connect to one another over the opening <NUM>.

The bridge <NUM> extends into body <NUM> at the opening <NUM> and is supported by an interior surface <NUM> of the passage <NUM> so as to prevent movement along an axis <NUM> of the passage, in a radial direction of the passage and/or in an angular direction in relation to the central axis <NUM>. In various embodiments, the interior surface <NUM> can comprise a ledge <NUM> that the bridge contacts where the ledge <NUM> prevents further movement of the bridge into the passage <NUM>.

A bridge <NUM> that extends into the passage <NUM> can be held in place by any appropriate means, such as by one or more of gravity, friction with the passage <NUM>, contact with ridges <NUM>, contact with a ledge <NUM>, glue, cement, welding and molding or machining in place. In some embodiments, bridge <NUM> can be a separate part that can then be installed in the space between the ridges <NUM> or into passage <NUM>. In some embodiments, the bridge <NUM> can be made as a part of the body <NUM> of plug <NUM> as a unitary construction such as by molding the bridge <NUM> into the body <NUM> when the body <NUM> is molded, machining the features of the bridge <NUM> into the body <NUM>, or providing material and/or a portion of the features of the bridge <NUM> as a part of constructing the body <NUM> as a laminated part. In some embodiments, the bridge <NUM> can be made by making a portion of the bridge <NUM> as a separate part and a portion as a part of the body as a unitary construction.

The partition <NUM> can be a body with a porous structure making it a porous partition that allows fluid to pass through. Examples of partitions can include bodies comprising fritted disks, filter elements, and the like. The partition <NUM> can be sized and configured to be supported by the ridges <NUM> and bridge <NUM> while extending to the edge of the circumferential surface <NUM> of body <NUM>. However, in some embodiments where first surface <NUM> includes optional peripheral rim <NUM>, the partition <NUM> can be located in a central opening <NUM> defined by the first surface <NUM> with the peripheral rim <NUM> at a periphery of the central opening, and can be supported by the ridges <NUM> and bridge <NUM> while substantially filling the central opening <NUM> in the body <NUM> above the top surface <NUM> of the ridges <NUM> and below the top face <NUM> of peripheral rim <NUM>, such as shown in <FIG>, <FIG> and <FIG>. In some embodiments, the partition <NUM> can be fitted to the body <NUM> to prevent the passage of medium between the partition <NUM> and the peripheral rim <NUM>.

In some embodiments, the partition <NUM> can have a cylindrical shape having a flat upper surface opposing a flat lower surface with a cylindrical surface extending between. Such a shape for partition <NUM> can be particularly suited for bodies <NUM> where the top surfaces <NUM>, <NUM> of the ridges <NUM> and bridge <NUM> form a substantially flat surface that is perpendicular to the circumferential surface <NUM> and where optional peripheral rim <NUM> is present. However, alternate shapes can also be used as desired by a designer of chromatography columns. Some particularly suitable shapes include those that have a contoured lower surface that is sized and configured to follow the contours of the top surface <NUM> of the ridges <NUM> and top surface <NUM> of bridge <NUM>. In some embodiments, suitably contoured surfaces can include those where the top surfaces <NUM>, <NUM> of the ridges <NUM> and bridge <NUM> are lower or higher in the center of the top surface <NUM>. In some embodiments, the upper and/or lower surface of the partition can be curved or domed. In some embodiments, a second porous partition can be present such that the mobile phase flows through one and then the other, such as through the first porous partition then the second porous partition at the inlet and through the second porous partition then the first porous partition at the outlet of the column. In some embodiments, the first and second porous partitions can be in contact with one another. In some embodiments, the first and second porous partitions can have a different pore size from one another, such as where the porous partition closer to the stationary phase has smaller or larger pores than the other porous partition.

A passage <NUM> through the body <NUM> connects the opening <NUM> in the first surface <NUM> with an opening <NUM> in the second surface, and is configured to provide a flow path from the first surface <NUM> to the second surface <NUM>. In some embodiments, more than one opening <NUM> can be present in the first surface <NUM> that the passage <NUM> connects to the opening <NUM> in the second surface. In some embodiments, the number of openings <NUM> in the first surface can be equal to the number of ridges <NUM>.

The openings <NUM> in the first surface can be located in a central portion of the first surface <NUM> or in a more peripheral location. Suitable locations can include, but are not limited to adjacent to the first ends <NUM> of the ridges <NUM> and adjacent to the bridge <NUM>.

In some embodiments, passage <NUM> can comprise a plurality of channels that connect distinct openings <NUM> in the first surface with a single or with multiple distinct openings <NUM> in the second surface.

The body <NUM>, the ridges <NUM>, the bridge <NUM> and the partition <NUM> can be any suitable material, each being selected independently of the other. However, in some embodiments it can be desirable to use a material for at least one or all of the body <NUM>, the ridges <NUM>, the bridge <NUM> and the partition <NUM> that is resistant to accumulation of components of the mobile phase or sample, as such accumulation can lead to changes in the quality of separation for the chromatography column. Accordingly, in various embodiments, materials such as metals or polymers or ceramics can be used. Suitable metals can include, but is not limited to, stainless steels, nickel and nickel alloys, titanium and titanium alloys, etc. Suitable ceramics can include but is not limited to, silica, alumina, silicon nitride, aluminum nitride, etc. Suitable polymers can be glass-filled or not glass-filled. Polymers can include, but is not limited to, fluoropolymers, polyolefins, polyesters, polyamides, etc. In some preferred embodiments, the polymer can be or include polyvinylidene fluoride (PVDF), polypropylene (PP), High density polyethylene (HDPE), low density polyethylene (LDPE), polyvinylchloride (PVC), polyethylene terephthalate (PET),ultra-high molecular weight polyethylene (UHMW), polyamide (PA, including grades such as Nylon <NUM>), polyetheretherketone (PEEK), polysulfone (PSU), polyester, thermoplastic elastomer (TPE), polyurethane (PUR), polyimide (PI, including grades such as those suitable for structural shapes including sintered shapes) or polyetherimide (PEI, including grades such as Ultem) or combinations thereof. (preferred forms of polyimide can include those that are suitable for making structural shapes. ) In various embodiments, one or more of the body <NUM>, the ridges <NUM>, the bridge <NUM> and the partition <NUM> can comprise one or more of these suitable materials.

Two chromatography columns were prepared from stainless steel tube having a <NUM> internal diameter (<NUM>/<NUM>" outer diameter) and <NUM> total length with a plug in one end and a porous partition in each plug. The plug, ribs and bridge were polyvinylidene fluoride. The porous partition was HDPE. The dimensions of each plug are as below.

The column was filled with media (non-porous spherical methacrylate particles ranging between <NUM> and <NUM> micron by packing at constant pressure of <NUM> bar. The first column used a plug without a bridge where the opening in the first surface took up the space where the bridge would have been. The second column used a plug that included a bridge as shown in <FIG>.

After packing each column, the column was disassembled and the porous partition for each column was inspected. <FIG> shows the porous partition of the first column (plug without bridge) and <FIG> shows the porous partition of the second column (plug with bridge). The porous partition associated with the plug without a bridge shows a hole <NUM> through the porous partition at a location between the first ends of the ribs. The porous partition associated with the plug with a bridge did not have a hole through the porous partition.

Having now described the invention in accordance with the requirements of the patent statutes, those skilled in this art will understand how to make changes and modifications to the present invention to meet their specific requirements or conditions.

Use of language such as "about", "approximately", "substantially" are intended to carry the meaning as understood by a person of skill in the art in the context presented where small changes can occur to a numerical value or a comparison of parts or values so described which do not change the functioning of the device, unless the context implies a more specific value. In situations where a person of skill would require further guidance, a variation of <NUM>% would be intended. In addition, where numerical values are provided, or where one dimension or value is described as the same as another, the value can be exactly the value provided or within a tolerance of <NUM>% or the equivalent dimensions or values can be exactly the same or within a tolerance of <NUM>%.

Sharp corners shown in the drawings can be replaced with rounded corners, beveled corners, etc., such as at the transition between the first surface and the opening in the first surface, as well as at other locations throughout the figures, each corner being independently determined as rounded or sharp. Rounded corners can in some embodiments have a radius of <NUM> or larger or smaller radii.

Claim 1:
A chromatography plug (<NUM>) comprising:
a body (<NUM>), the body (<NUM>) comprising:
a first surface (<NUM>);
a second surface (<NUM>) opposing the first surface (<NUM>);
a passage (<NUM>) through the body (<NUM>) extending from an opening (<NUM>) in the first surface (<NUM>) to an opening (<NUM>) in the second surface (<NUM>); and
a circumferential surface (<NUM>) extending from the first surface (<NUM>) to the second surface (<NUM>);
a plurality of ridges (<NUM>), located on the first surface (<NUM>), wherein each of the plurality of ridges (<NUM>) having a first end (<NUM>) and an opposed second end (<NUM>), and the first end (<NUM>) of each of the plurality of ridges (<NUM>) being closer to one another than the second ends (<NUM>) of each of the plurality of ridges (<NUM>);
characterized in that
a bridge (<NUM>) is located between the first ends (<NUM>), said bridge (<NUM>) extends into the body (<NUM>) at the opening in the first surface (<NUM>) of the passage (<NUM>), said bridge (<NUM>) has a top surface (<NUM>) external to the body (<NUM>) and facing away from the first surface (<NUM>), and said bridge (<NUM>) extends over at least a portion of opening (<NUM>) in first surface (<NUM>) and extends into opening (<NUM>).