Pre-assembled separation columns

Abstract

There is provided an integrated system for liquid separation, such as LC, CE, affinity chromatography, and ion exchange chromatography, comprising a column and end-fittings embedded in a plastic material, such as a thermoplastic polymer. The system may further comprise an electrospray emitter directly connected with the outlet of the column, wherein a substantial part of the emitter is covered with the polymer material. There is also provided a method by which a separation column along with the accompanying end fittings for connection with adjacent liquid conduits is embedded in a polymer matrix. This configuration e.g. ensures that the factory-made, correct attachment of the fittings to the column is preserved (since the matrix prevents further user intervention, accidental or otherwise). Accordingly, the responsibility for the correct attachment of the fittings is shifted from the end user to the manufacturer.

Claims

1. An integrated separation column comprising: an electrospray emitter; a separation column; an first union coupling the electrospray emitter and the separation column; a second union configured to couple the separation column to a chromatography system; and a thermo sensor and heater in contact with the separation column; wherein the separation column, the first union, and at least part of the electrospray emitter, the thermo sensor and heater, and at least a portion of the second union are embedded in a plastic material, the plastic material extends continuously to cover at least the first union, the separation column, and the thermo sensor and heater and the plastic material forms a housing.

2. The integrated separation column of claim 1, wherein the electrospray emitter is based on a glass capillary.

3. The integrated separation column of claim 1, wherein the plastic material is a thermoplastic material.

4. The integrated separation column of claim 3, wherein the thermoplastic material comprises polyamide and/or polyurethane.

5. The integrated separation column of claim 3, wherein the plastic material is the fluoropolymer, and the fluoropolymer comprises perfluoroamines (PFA) or fluorinated ethylene-propylene copolymer (FEP).

6. The integrated separation column of claim 5, wherein the plastic material is the duroplastic material or compound, and the duroplastic material or compound comprises polyimide or liquid crystal polymers (LCP).

7. The integrated separation column of claim 1 further comprising an RFID-tag.

8. The integrated separation column of claim 1 wherein the housing is formed by injection molding of the plastic material.

Description

BRIEF DESCRIPTION OF DRAWINGS

(1) FIG. 1 shows an arrangement with an HPLC column being part of the arrangement with two conduits and fittings. One conduit is the electrospray emitter and the other conduit is the column body.

(2) FIG. 2 shows a view of the arrangement of FIG. 1, but with the forming tool (in two halves) encompassing the arrangement with a surrounding molding part.

(3) FIG. 3 shows a three-dimensional view of the arrangement of FIG. 2 completely fabricated and without the forming tool. Also shown is the frame (or adapter) that fits to the outer shape of the now embedded column and fitting. The pin for the HV connection can be seen underneath the fitting that connects the electrospray emitter and the column body.

(4) FIG. 4 shows a three dimensional view of an alternative arrangement where an integrated emitter and column is embedded along with magnets to provide a snap-on connection to a frame, as well as a gas flow line that points towards the emitter tip such that it can pneumatically assist the desolvation of the sprayed droplets, and also shown is an annular counter electrode that can be used to optimize the electric field lines between the emitter and the inlet orifice.

DETAILED DESCRIPTION OF THE INVENTION

(5) The arrangement as shown in FIGS. 1 and 2 comprises a pre-assembled HPLC column (1) with fittings (2, 3). The molding part (4) comprises a plastic material, for example, a thermoplastic material, for example, polyamide and polyurethane based MacroMelt™. The plastic material is adapted for being formed with a forming tool (5) comprising a mold (6). The mold (6) comprises an inner surface (7). FIG. 2 shows a view of the arrangement of FIG. 1, but with the closed forming tool (5). In some embodiments, the plastic material can be melted completely and afterwards cooled down to ambient temperature. Therefore, the plastic material can realize a chemical bond with the outer surfaces of the column and fittings.

(6) FIG. 3 shows a three-dimensional view of the arrangement of FIG. 2 completely fabricated and without the forming tool. Also shown is the frame (or adapter) that fits to the outer shape of the now embedded column and fitting. The pin for the HV connection can be seen underneath the fitting that connects the electrospray emitter and the column body. Specifically there is shown an emitter 1, a sleeve 2 that fits the emitter, a cradle 3 that is mounted on electrospray source and provides means of snap-on fitting of embedded column via magnets, a chromatography column 4 embedded in plastic, a high voltage connector pin 5, an embedded union 6 that connects column and emitter, a partly embedded union 7 that connects column and transfer line from chromatography system.

(7) FIG. 4 shows a three dimensional view of an alternative arrangement where an integrated emitter and column is embedded along with magnets to provide a snap-on connection to a frame, as well as a gas flow line that points towards the emitter tip such that it can pneumatically assist the desolvation of the sprayed droplets, and also shown is an annular counter electrode that can be used to optimize the electric field lines between the emitter and the inlet orifice. Specifically there is shown an emitter 1, a counter electrode 2, such as an annular disc that assists in controlling the electrical field lines between the column/emitter arrangement and the inlet orifice of the mass spectrometer, an exit opening 3 of the gas conduit (a stream of air or inert gas, e.g. nitrogen, may be used to facilitate desolvation of the electrosprayed droplet), a plastic matrix cast 4 around the union that connects emitter and column, a union 5 that connects emitter and column (made from metal or polymer material), a column tube 6 (not embedded in the present drawing, made from polymer, metal, or glass tubing), a magnet 7 (with dual purpose: i) enables snap-on fitting to adapter frame; and ii) connects high voltage to the electrospray emitter), a magnet 8 (with dual purpose: i) enables snap-on fitting to adapter frame; and ii) connects high voltage to the counter electrode), and finally an entrance opening 9 of the gas conduit.

(8) According to the present invention, devices and techniques for HPLC applications are provided. More particularly, the invention provides a method and system for performing separation of compounds. Merely by way of example, the invention has been applied to a high pressure liquid chromatography process. But it would be recognized that the invention has a much broader range of applicability.

(9) Embodiments may comprise one or more of the following: a part surrounding an HPLC column with end fittings that are plastified and molded within a forming tool for forming or for shaping the form of the integrated column and for fixing the fittings (nuts and bolts). The molding part comprises a plastic material. Advantageously, this technique enables sealing and positioning of said fittings and column. Advantageously, the forming tool can form the shape, for example the outer shape, of the integrated column to a desired shape with a good dimensional stability and a high reproducibility. Additionally, close tolerances can be held or maintained, for example, by exactly adjusting the process parameters like the temperature and the detention time within the forming tool.

(10) The molding part can be realized as a pre-formed part, wherein the shape of the pre-formed part is adapted to the shape of the column and fittings and of the forming tool. The pre-formed molding part can be plastified by heating the plastic material above or beyond the softening temperature and bringing it in its softening range for making it soft and pliable. Advantageously, the plastified plastic material can be evenly formed to the outer surfaces of the column and fittings. This enables a homogenous force distribution across the surfaces. Besides this, the mechanical stress after forming can be reduced.

(11) In embodiments, the pre-formed molding part can comprise two or more component parts, wherein said component parts are joined to each other.

(12) Most advantageously, the molding part can be realized by injecting molten plastic material into a mold and allowing this to cool to such temperature where the plastic forms a stable solid which may be flexible or entirely rigid depending on the chosen chemical composition of the plastic material.

(13) In embodiments, the forming tool is equipped at least partly with at least one HPLC column and fittings and with at least one pre-formed part. The pre-formed part comprises the plastic material and is adapted to be formed for producing the sheath around the column and fittings. Advantageously, the pre-formed part can be easily produced with a relative low exactness, for example, by extruding, injection molding, or alike and is thus cost effective.

(14) Advantageously, the formed columns fulfill a given set of tolerances. The dimensional consistency is guaranteed by forming the pre-formed molding part or the molten plastic by the forming tool. One forming tool can be used for different insets, different types of conduits, for example, polymer tubing, capillaries, glass capillaries, fused silica capillaries, rods, bars, needles, syringes or alike.

(15) Before forming the molding part around the column and fittings, an outer surface of the column and fittings can be at least partly surrounded with the pre-formed molding part. After forming, the functional element can adhere to the outer surface of the conduit, for example, by frictional forces, shrink forces and/or a chemical bond. For forming the molding part around the column and fittings, the forming tool can be closed for exerting pressure on the softened pre-formed part, or, as the case may be, allow a molten plastic to be injected under pressure.

(16) The tool can be closed and heated together with the plastic material of the pre-formed part. Possibly, pressure can be exerted on the plastic material by thermal expanding the plastic material by heating it within the closed forming tool. Besides this, the pressure can be exerted by a moving piston of the forming tool. After forming, the forming tool can be opened. Possibly, the tool can be opened before cooling down the already formed molding part. By this, the production quantity per time unit can be increased. The step of cooling down the functional element to ambient temperature can be parallelized with the step of forming the next unit. Or, for adjusting, for example, a lower and/or exacter temperature gradient, the plastic material can be cooled down within the forming tool. The cooling step can also be forced actively by well known practices like air cooling, or fluidic cooling of the parts, or surrounding parts, or with a thermocouple.

(17) Advantageously, the plastic material can be shrunk on the outer surface of the column and fittings by cooling the plastic material down to ambient temperature.

(18) Embodiments may comprise one or more of the following. The plastic material can be heated within the forming tool close to or above the melting temperature for bringing the plastic material to the softening range or for melting the plastic material. By this, a chemical bond between the outer surface and the plastic material is possible. For avoiding a similar chemical bond of the plastic material at the boundary point of the inner surface of the mold to the forming tool, one can choose a tooling material which will not cling together with the plastic material or the mold and/or the forming tool can be coated with an according release agent.

(19) The plastic material can be a thermoplastic material or compound, for example polyamide and polyurethane, polyetheretherketone (PEEK), flouropolymers for example perfluoroamines (PFA) or flourinated ethylene-propylene copolymer (FEP), duroplastic material or compound for example polyimide, LCP (liquid crystal polymers), and/or perfluoroamines (PFA), comprising advantageous material properties; for example, high persistence against aggressive solvents and good properties for sealing.

(20) Preferably the plastic material comprises molding compounds are thermoplastic hotmelts based on polyamide. The products of the Macromelt® series are exciting not only technically but also ecologically as they are produced from renewable raw materials. No chemical reactions take place during application and no solvents are released. Macromelt® hotmelts are processed at temperatures of 130 to 240° C. and can be used at temperatures from −40 to +140° C. Adhesion to PA, PBT, PVC and similar polar substrates is very good. Macromelt® hotmelts may be distinguished from other hotmelts by their exceptional mechanical properties. With a high Shore hardness, it produces a plastic-like surface, which is achieved by its high crystalline shares. Macromelt® hotmelts have extremely good mechanical and chemical strength and an excellent adhesion to the materials used to manufacture separation columns, including PEEK, metal, and PVC.

(21) Additionally, the plastic material can be coated after forming with a sealing material, for example, with silicone, rubber, Teflon®, epoxy, or alike.

(22) Further embodiments of the present invention relate to an arrangement of a coupling for bringing conduits in communication. The coupling comprises at least one conduit adapted for conducting a medium, for example, an HPLC column, and an element, such as a fitting with ferules, adapted for bringing the conduit in communication with another conduit, for example, an electrospray needle.

(23) In an alternative embodiment of the present invention only the fittings and/or minor parts of the conduits are embedded in the molding material in order to prevent the disassembly of the arrangement and shield from the electric HV potential, whereas; in this embodiment the actual conduits, which may be the column body or a transfer line, may be so long as to be impractical or impossible to include in the embedded volume in their entirety.

(24) Column Dimensions

(25) The chromatography columns of the present invention may have a variety of sizes depending on the use of the chromatography column. For example, chromatography columns of the present invention may have any height (also referred to herein as the column length), although columns almost invariably have an overall height of less than 3 meters (m) and usually less than 1 meter and typically a height around 10 cm. In some embodiments, chromatography columns of the present invention have a height (or length) ranging from about 0.50 mm to about 1.0 m.

(26) Chromatography columns of the present invention may also have a tubular wall structure of an overall thickness that varies, depending on the requirements of the column (e.g., the pressure capacity). Typically, chromatography columns of the present invention have a tubular wall structure overall thickness of up to about 50 mm. In some embodiments, chromatography columns of the present invention have a tubular wall structure overall thickness ranging from about 25 μm to about 10 mm.

(27) Chromatography columns of the present invention may be constructed from the above-referenced materials in order to withstand an internal pressure that varies depending on the end use of a given column. Typically, chromatography columns of the present invention are constructed to have a pressure capacity of up to about 50,000 psig. In some embodiments, chromatography columns of the present invention are constructed to have a pressure capacity ranging from about 500 to about 50,000 psig.

(28) Fittings

(29) Fittings as used for the present invention may be constructed from a wide range of polymer materials where often a hard and chemically inert polymer such as PEEK is preferred. Alternatively fittings may be made of a range of metals where stainless steel and titanium usually are the preferred materials. For the purpose of making electrical contact between an electrospray emitter and the power supply that supplies the electrospray potential as described herein, it is advantageous that the fitting materials be conductive, which means metal is usually the material of choice.

(30) Fittings include ferrules or gaskets that provide a seal between the body of fitting and the conduits that are to be connected. The build-up of dead-volumes or un-swept volumes inside the conduits and fittings is best avoided by butt-connecting all conduits, which leads to the best chromatographic performance. Despite the foregoing, conduits that are joined inside the fittings, may still be kept apart by small distances made up by the thickness of filter-disks, metal grids, or similar without noticeable deterioration of the chromatographic resolving power of the integrated unit.

(31) Electrospray Emitter

(32) The electrospray emitters as used for the present invention may be made of glass tubing which may end in a sharp or a blunt tip. It is usually preferable to have a sharp and tapered tip such as that obtained when using an automated capillary puller (e.g. from Sutter Instrument, Inc., Novato, Calif., USA) since such emitters provide a more stable spray than blunt emitters do. Typically such tapered emitters have an outer diameter of about 360 am and an inner diameter of 5 μm to 100 μm whereas the orifice at the tapered tip is usually around 1 μm to 15 μm. The length of such emitters is usually between 30 mm and 60 mm but may also be longer or shorter.

(33) Still better performance is usually obtained from emitters that are made of a conductive material, hereunder steel, and bi-modal materials such as gold and nickel. Some embodiments of the present invention preferable use stainless steel emitters than have an outer diameter between 100 μm and 500 μm and an inner diameter between 5 μm and 100 μm.

Example 1

(34) Preparation of a Chromatography Column Embedded in a Thermoplastic Polymer

(35) An integrated HPLC column with electrospray needle having the structure shown in FIG. 3 was manufactured by following injection molding steps as previously described. The specifications are given below.

(36) Outer diameter of column: 360 μm

(37) Inner diameter of column: 75 μm

(38) Length of column: 10 cm

(39) Material of column tubing: Polyimide coated fused silica glass

(40) Packing material of column (stationary phase): ReprosilPur C18, 3 μm beads, 120 nm pores

(41) Outer diameter of emitter: 150 μm

(42) Inner diameter of emitter: 20 μm

(43) Length of emitter: 4 cm

(44) Material of emitter: Stainless steel, electropolished tip

(45) Embedding material: polyamide or polyurethane based MacroMelt™

(46) Process: Injection molding, using a Moldman handset

(47) Forming temperature: about 180° C. to 240° C.

(48) Forming time: around 30 sec.

(49) Cooling temperature: to ambient

(50) Cooling time: as required

(51) Molds: aluminium, manufactured in-house

(52) Molding process done in 3 or 4 steps in sequence.