[go: up one dir, main page]

WO2024229239A1 - Dispositif de manipulation de fluide haute pression pour chromatographie en phase liquide - Google Patents

Dispositif de manipulation de fluide haute pression pour chromatographie en phase liquide Download PDF

Info

Publication number
WO2024229239A1
WO2024229239A1 PCT/US2024/027435 US2024027435W WO2024229239A1 WO 2024229239 A1 WO2024229239 A1 WO 2024229239A1 US 2024027435 W US2024027435 W US 2024027435W WO 2024229239 A1 WO2024229239 A1 WO 2024229239A1
Authority
WO
WIPO (PCT)
Prior art keywords
tube
component
handling device
fluid handling
pressure fluid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/US2024/027435
Other languages
English (en)
Inventor
Daniel Czarnecki
Michael Keller
Graham SHELVER
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Idex Health and Science LLC
Original Assignee
Idex Health and Science LLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Idex Health and Science LLC filed Critical Idex Health and Science LLC
Publication of WO2024229239A1 publication Critical patent/WO2024229239A1/fr
Anticipated expiration legal-status Critical
Pending legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/60—Construction of the column
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/04—Preparation or injection of sample to be analysed
    • G01N30/16—Injection
    • G01N30/22—Injection in high pressure liquid systems
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
    • B01D15/08—Selective adsorption, e.g. chromatography
    • B01D15/10—Selective adsorption, e.g. chromatography characterised by constructional or operational features
    • B01D15/22—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the construction of the column
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/50—Conditioning of the sorbent material or stationary liquid
    • G01N30/52—Physical parameters
    • G01N2030/522—Physical parameters pressure
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/04—Preparation or injection of sample to be analysed
    • G01N30/16—Injection
    • G01N30/20—Injection using a sampling valve
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/26—Conditioning of the fluid carrier; Flow patterns
    • G01N30/28—Control of physical parameters of the fluid carrier
    • G01N30/32—Control of physical parameters of the fluid carrier of pressure or speed
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/50—Conditioning of the sorbent material or stationary liquid
    • G01N30/56—Packing methods or coating methods

Definitions

  • the fluid handling device may be particularly adapted for micro and/or nano-scale chromatography applications, to provide for liquid chromatography columns that have an internal diameter equal to or less than 1000 ⁇ m.
  • HPLC High-performance liquid chromatography
  • a liquid used to carry the sample through the chromatography system is referred to as the “mobile phase”.
  • the components of the sample may be separated in a “column”, that is typically a tube packed with particulate material to which different components have varying degrees of affinity.
  • the packing material is referred to as the “stationary phase” and is usually a silica or polymer-based medium and may be coated with chemical functionality to drive desired chemical affinity with components of the sample.
  • UHPLC systems are often operated as micro-scale, capillary-scale or nano-scale HPLC, with mobile phase flow rates in the range of about 100 nL/min to 100 ⁇ L/min and column inner diameters of between 25- Atty. Docket No.8360.002PCT1 1000 ⁇ m.
  • Some, though not necessarily all, of the benefits that result in this reduction in size include reduced solvent consumption (both an environmental and economic benefit), increased sensitivity, reduced stationary phase usage, improved compatibility with mass spectrometry, and analysis of smaller sample quantities.
  • stainless steel tubing of sufficient quality is typically unavailable in these dimensions, alternative materials such as fused silica may be used for column fabrication. However, such materials are fragile, flexible, and require special handling precautions.
  • Chip patterned substrate, or “chip” based design in which flow paths of desired dimensions are created within a substrate akin to an electrical equivalent such as a computer chip.
  • the flow paths in a chip-based design are typically formed in the substrate through chemical etching, lithography, or CNC machining, and are usually provided with square, rectangular, D-shaped, trapezoidal, or other polygonal cross-sectional shapes.
  • the high-pressure fluid handling device includes a housing, a tube, and a stationary phase medium.
  • the housing includes a first component with a first interface surface and a second component with a second interface surface. The first and second components are securable to one another with the first and second Atty.
  • the housing includes a channel extending through the first component to and along the interface.
  • the tube extends along the channel.
  • the tube defines a lumen with a substantially circular cross- section having a lumen diameter equal to or less than 1000 ⁇ m.
  • the stationary phase medium is positioned in the lumen.
  • the stationary phase medium is suitable to chromatographically separate compounds present in a liquid sample.
  • a high-pressure fluid handling device An inlet is configured to receive a liquid sample.
  • a housing includes first component having a first interface surface and a channel extending through the first interface surface.
  • the housing includes a second component having a second interface surface.
  • the first and second components are securable to one another with the first and second interface surfaces in facing relationship with one another to form an interface therebetween.
  • a tube is positioned within the channel of the first component.
  • the tube defines a lumen with a substantially circular cross-section.
  • a stationary phase medium is disposed within the lumen of the tube.
  • the stationary phase medium is suitable to chromatographically separate compounds present in a liquid sample.
  • An outlet port is fluidically coupled to the inlet port via the tube.
  • FIG.1 is an isometric view of a high-pressure fluid handling device, according to some embodiments.
  • FIG.2 is a schematic view of a liquid chromatography system including a high-pressure fluid handling device, according to some embodiments. Atty.
  • FIG.3 is an isometric view of a first component and a second component of a high- pressure fluid handling device, according to some embodiments.
  • FIG.4 is an isometric bottom view of a first component and a second component of a high-pressure fluid handling device, according to some embodiments.
  • FIG.5 is an isometric cross-sectional view of a high-pressure fluid handling device, according to some embodiments.
  • FIG.6 is a magnified, isometric cross-sectional view of a radiused bend of a tube in a high-pressure fluid handling device, according to some embodiments.
  • FIG.7 is a cross-sectional view of a tube and a channel extending through a high- pressure fluid handling device, according to some embodiments.
  • FIG.8 is an isometric bottom view of a first component of a high-pressure fluid handling device, according to some embodiments.
  • FIG.9 is a cross-sectional side view of a high-pressure fluid handling device with a tube terminating at an outlet on an outer surface of the high-pressure fluid handling device, according to some embodiments.
  • FIG.10 is a cross-sectional side view of a multi-walled tube of a high-pressure fluid handling device, according to some embodiments.
  • FIG.11A is a cross-sectional view of a high-pressure fluid handling device with a membrane placed over an outlet to form a cavity, according to some embodiments.
  • FIG.11B is a cross-sectional view of a high-pressure fluid handling device with a stationary phase retained in the cavity, according to some embodiments.
  • FIG.11C is a cross-sectional view of a high-pressure fluid handling device with the membrane removed to expose the cavity, according to some embodiments.
  • FIG.11D is a cross-sectional view of a high-pressure fluid handling device with a porous frit installed within the cavity to retain the stationary phase inside the tube, according to some embodiments.
  • FIG.12A is a chromatogram of a fluid handling device packed with a stationary phase at 1,500 psi, according to some embodiments.
  • FIG.12B is a chromatogram of a fluid handling device packed with a stationary phase at 16,500 psi, according to some embodiments.
  • Atty. Docket No.8360.002PCT1 FIG.13 is a flow chart of a method of forming a high-pressure fluid handling device, according to some embodiments.
  • FIG.14 is a flow chart of a method for packing a tube of a high-pressure fluid handling device, according to some embodiments.
  • the present disclosure describes a fluid handling device for use in liquid chromatography.
  • the high-pressure fluid handling device comprises a housing having a small- diameter fluid passageway extending through the housing.
  • the small-diameter fluid passageway is configured to withstand high-pressure (i.e., includes thick side walls and/or captured by the housing to support high-pressure loads).
  • the small-diameter fluid passageway is configured for use on micro-scale, capillary-scale, and/or nano-scale liquid chromatography, with a cross- sectional diameter of equal to or less than 1000 ⁇ m.
  • the small-diameter fluid passageway extends along a length of the high-pressure fluid handling device, such that the length of the small-diameter fluid passageway is at least 100 times the diameter of the small-diameter fluid passageway.
  • the high aspect ratio (length-to-diameter) and/or the micro-scale/nano-scale diameter of the fluid passageway makes drilling a hole through the housing impractical.
  • the housing includes a first component with a first interface surface and a second component with a second interface surface.
  • the first and second components are secured together with the first and second interface surfaces in a facing relationship to form an interface therebetween.
  • the housing includes a channel extending through the first component and along the interface.
  • a tube defining a small-diameter fluid passageway having a substantially circular cross-section is positioned in the channel.
  • the fluid passageway is packed with a stationary phase medium suitable for chromatographic separation of a liquid sample.
  • FIG.1 is an isometric view of a high-pressure fluid handling device 10, according to some embodiments.
  • the high-pressure fluid handling device 10 includes a housing 12 having a first component 14 and a second component 16 forming an interface 38 therebetween.
  • the high- pressure fluid handling device 10 includes an inlet block 18 secured to the first component 14 and/or the second component 16 via one or more fasteners 24.
  • the inlet block 18 includes an inlet tube receptacle 19 configured to receive a liquid sample and/or secure to an inlet tube (or a conduit) for transporting the liquid sample.
  • the high-pressure fluid handling device 10 includes an outlet block 22 secured to the first component 14 and/or the second component 16 via one or more fasteners 24.
  • the outlet block 22 includes an outlet tube receptacle 23 configured to output a liquid sample and/or secure to an outlet tube (or a conduit) for transporting the liquid sample.
  • the inlet and outlet tube receptacles 19, 23 are configured to engageably receive tube connecting hardware that may effectively establish a fluidic connection.
  • Inlet and outlet tube receptacles may be threaded to threadably engage with tube connecting hardware.
  • the high-pressure fluid handling device 10 may be used in connection with a variety of fluid transfer applications.
  • the high-pressure fluid handling device 10 may be particularly well suited for liquid chromatography applications, such as high performance liquid chromatography (“HPLC”) and/or ultra-high performance liquid chromatography (“UHPLC”).
  • HPLC high performance liquid chromatography
  • UHPLC ultra-high performance liquid chromatography
  • the high-pressure fluid handling device 10 is configured to receive a liquid sample through the inlet block 18. The liquid sample travels through the high-pressure fluid handling device 10 and exits the high-pressure fluid handling device 10 through the outlet block 22.
  • the high-pressure fluid handling device 10 may be referred to as a “chip” (for chip- based chromatography applications) or, more generically, a “manifold”.
  • FIG.2 is a schematic view of a high-pressure liquid chromatography system 102 including the high-pressure fluid handling device 10, according to some embodiments.
  • the high- pressure liquid chromatography system 102 includes a solvent reservoir 104 (and/or eluent reservoir), a degasser 106 for degassing the liquid solvent/eluent, a pump, such as a high pressure pump 108, for pumping the degassed liquid solvent/eluent to an injection valve 110 where sample from a sample container or autosampler 112 is injected into the solvent/eluent stream and delivered to a column 114 for chromatographically separating the sample.
  • the plug(s) of Atty is a schematic view of a high-pressure liquid chromatography system 102 including the high-pressure fluid handling device 10, according to some embodiments.
  • the high- pressure liquid chromatography system 102 includes a solvent reservoir 104 (and/or eluent reservoir), a degasser 106 for degassing
  • the high-pressure liquid chromatography system 102 optionally includes additional or different components, as is well known in the art, such as flow cells for optical analysis, in-line degassers, sample loops, etc.
  • the high-pressure fluid handling device 10 described with reference to the drawing figures encompasses a portion of chromatographic system 102 between injection valve 110 and analytical instrument 116, according to some embodiments.
  • the high-pressure fluid handling device 10 may contain, be comprised of, or integrate directly with additional elements without requirement for external tubes, which can include, but are not limited to, a flow cell for optical detection, a heating or cooling element to control temperature, and/or an emitter tip for use with mass spectrometry, according to some embodiments.
  • FIG.3 is an isometric view of the first component 14 and the second component 16 of the high-pressure fluid handling device 10, according to some embodiments.
  • the first component 14 includes an outer surface 15, an inlet opening 30, an outlet opening 32, one or more mounting receptacles 26, and one or more alignment features 28, according to some embodiments.
  • the high-pressure fluid handling device 10 is configured to facilitate fluid-tight seals between an inlet tube (not shown) and the inlet opening 30, as well as between an outlet tube (not shown) and the outlet opening 32.
  • the inlet and outlet blocks 18, 22 are secured to the first component 14 in a manner that prevents fluid from escaping between the respective inlet and outlet block 18, 22 and the first component 14. Accordingly, the inlet and outlet tubes secured to respective inlet and outlet blocks 18, 22 with coupling hardware that prevents fluid leaks out from receptacles 19, 23 convey fluid (namely mobile phase) to the inlet opening 30 and from the outlet opening 32.
  • FIG.4 is an isometric bottom view of the first component 14 and the second component 16 of the high-pressure fluid handling device 10, according to some embodiments.
  • the second component 16 includes an outer surface 17, one or more mounting receptacles 26, and one or more alignment features 28, according to some embodiments.
  • the one or more mounting receptacles 26 positioned on the first component 14 align with the one or Atty. Docket No.8360.002PCT1 more mounting receptacles 26 positioned on the second component 16.
  • the one or more alignment features 28 positioned on the first component 14 align with the one or more alignment features 28 positioned on the second component 16.
  • the one or more mounting receptacles 26 and/or one or more alignment features 28 extend through the first component 14 and the second component 16 of the housing 12 to align and secure the first component 14 and the second component 16 together.
  • the fasteners 24 extend through the one or more mounting receptacles 26 to couple the first component 14 and the second component 16 together and a stud/pin (not shown) can extend through the one or more alignment features 28 to align the first component 14 relative to the second component 16.
  • the first component 14 and the second component 16 can be aligned and fastened together without mounting receptacles 26 and/or alignment features 28.
  • the forces required to maintain a fluid-tight seal are provided by external means (not shown), e.g., a clamping mechanism.
  • the high-pressure fluid handling device 10 may be configured to facilitate fluid-tight seals directly between adjacent components of chromatography system 102, for instance, between the high-pressure fluid handling device 10 and the injection valve 110 and/or between the high-pressure fluid handling device 10 and the detection device 116, with or without the use of one or more of inlet and outlet tubes.
  • the isometric bottom view of FIG.4 shows the outer surface 17 of the second component 16.
  • FIGS.3-4 show the housing 12 including the first and second components 14, 16, the housing 12 may comprise several layers of the same or different materials to form the overall “chip” or “manifold” of the high-pressure fluid handling device 10.
  • the housing 12 may be constructed to define the interface 38 between two interfacial surfaces.
  • each of first and second components 14, 16 include a respective interface surface, with first component 14 including a first interface surface 34, and second component 16 including a second interface surface 36.
  • the first and second interface surfaces 34, 36 engage (or abut) each other at the interface 38.
  • the first component 14 and the second component 16 are securable to one another with the first interface surface 34 and the second interface surface 36 in a facing relationship with one other to form the interface 38.
  • the first and second Atty. Docket No.8360.002PCT1 components 14, 16 are securable to one another with the first interface surface 34 engaged with the second interface surface 36 to retain the tube 40 therebetween and to maintain an overall integrity of the fluid handling device 10.
  • the engagement between the first interface surface 34 and the second interface surface 36 is configured to avoid misalignment between the first and second components 14, 16.
  • the alignment features 28 pass through the entirety of the housing 12 and minimize/eliminate gaps or sharp features between the first interface surface 34 and the second interface surface 36.
  • FIG.5 is an isometric cross-sectional view of the high-pressure fluid handling device 10, according to some embodiments.
  • the high-pressure fluid handling device 10 includes a channel 20 extending through the first component 14 between the inlet opening 30 and the outlet opening 32, according to some embodiments.
  • the channel 20 is positioned at the outer surface 15 of the first component 14 at the inlet port 30 and the outlet port 32.
  • the channel 20 extends through the first component 14 from the outer surface 15 to the interface surface 34, in some embodiments.
  • the channel 20 is positioned along the interface surface 34, and in some embodiments, the channel 20 is formed via milling, cutting, laser etching, chemical etching, lithography, CNC machining, etc., of the interface surface 34.
  • the first housing 14 is formed via a mold or extrusion with the channel 20 formed in the mold/extrusion.
  • the channel 20 is formed solely in first component 14 (not through the second component 16), though it is contemplated that the channel 20 may be formed in one or more layers of the high-pressure fluid handling device 10.
  • the channel 20 may form one or more of a through-bore through at least one of the first and second components 14, 16, and/or a recess or groove in a surface of one or more of the first and second components 14, 16.
  • FIG.6 is a magnified, isometric cross-sectional view the high-pressure fluid handling device 10, according to some embodiments.
  • the high-pressure fluid handling device 10 includes a tube 40 positioned within the channel 20 and a radiused bend 21 of the channel 20.
  • the tube 40 is positioned within the channel 20 of the high-pressure fluid handling device 10 to extend through and/or along one or more of the first and second components 14, 16.
  • the tube 40 extends from the inlet opening 30 to the outlet opening 32.
  • Atty. Docket No.8360.002PCT1 so, tube 40 extends along the channel 20 through the first component 14 and along the interface 38.
  • the radiused bend 21 of the channel 20 is configured to transition the position of the channel 20 from the outer surface 15 to the interface surface 34 without sharp edges or abrupt directional changes that would disrupt fluid flow characteristics.
  • the radiused bend 21 may be between 5° and 180°, with the illustrated embodiment having the radiused bend 21 of 90°.
  • radiused bend 21 may be between 60° and 120°.
  • the tube 40 is fabricated from materials, and formed into configurations capable of establishing and maintaining the lumen diameters described below, including while following one or more radiused bends 21.
  • the tube 40 is fabricated from a biocompatible material such as, for example, stainless steel, titanium, poly ether-ether ketone, and combinations thereof, for example, poly-ether-ether-ketone lined stainless steel tubing.
  • a biocompatible material such as, for example, stainless steel, titanium, poly ether-ether ketone, and combinations thereof, for example, poly-ether-ether-ketone lined stainless steel tubing.
  • Other metal, metal alloy, polymeric materials, and combination materials are contemplated as being useful in the manufacture of the tube 40 as well as coated versions of the tube 40 where a coating has been applied to one or more surfaces of the tube 40, imparting beneficial properties, for example, chemical compatibility, bio-inertness, etc.
  • FIG.7 is a cross-sectional view of the tube 40 and the channel 20 extending through the high-pressure fluid handling device 10, according to some embodiments.
  • the tube 40 defines a lumen 42.
  • the lumen 42 has a substantially circular cross-sectional configuration. In some embodiments, the lumen 42 has a circular cross-section, wherein diameter dimensions along orthogonal radial axes in the lumen 42 are within 5% of one another, preferably within 3% of one another, and still more preferably within 2% of one another. In this manner, the precise configuration of the channel 20 is unimportant, so long as the tube 40 is positioned in channel 20 to provide a desired fluidic connection. As described above, a circular cross-sectional arrangement for the fluid passageway is most desirable because it facilitates expected and reproducible flow patterns and effects on the sample-bearing eluent. Thus, the tube is configured to maintain a substantially circular lumen cross-section when disposed in channel 20.
  • the lumen 42 defines a micro-scale, capillary scale, and/or nano- scale diameter configured for use in HPLC and/or UHPLC.
  • the lumen 42 has a lumen diameter of less than or equal to 1000 ⁇ m, according to some embodiments.
  • the Atty. Docket No.8360.002PCT1 lumen 42 has a lumen diameter of between 25-1000 ⁇ m, in some embodiments, the lumen 42 has a lumen diameter of between 25-500 ⁇ m, in some embodiments, the lumen 42 has a lumen diameter of between 25-250 ⁇ m, and/or in some embodiments, the lumen 42 has a lumen diameter of between 25-150 ⁇ m.
  • FIG.8 is an isometric bottom view of the first component 14 of the high-pressure fluid handling device 10, according to some embodiments.
  • the first component 14 includes the interface surface 34 with the channel 20 formed therein.
  • the tube 40 is positioned within the channel 20.
  • the tube 40 is brazed into the channel 20.
  • the tube 40 is brazed into the channel 20 such that gaps between the tube 40 and the channel 20 are filled with brazing metal.
  • the tube 40 is secured to the channel 20 with adhesive whereby gaps between the tube 40 and the channel 20 are filled with adhesive.
  • the channel 20 is formed entirely in the first component 14.
  • the interface surface 36 of the second component 16 does not include a recess or channel which forms part of the channel 20.
  • the interface surface 36 of the second component 16 is planar.
  • the tube 40 is disposed entirely within the channel 20 in first component 14. In other words, no portion of the tube 40 extends within a recess, channel, or other concave features of the second component 16. [0048] In some embodiments, positioning the channel 20 solely at the first component 14 (and not in the second component 16) is beneficial because it does not require perfect alignment between the first component 14 and the second component 16.
  • the channel 20 extended through both the first component 14 and the second component 16 (e.g., the first component 14 including a semi-circular channel and the second component 16 including a semi- circular channel), a near perfect alignment would be required between the first component 14 and the second component 16. If the alignment is off by micrometers, sharp edges would be formed along the fluid passageway, interfering with the liquid chromatography process. Therefore, positioning tube 40 solely in the first component 14 provides a substantially circular flow path without requiring near-perfect alignment along the entire length of the high-pressure fluid handling device 10. [0049] In some embodiments, positioning the tube 40 between the first component 14 and the second component 16 is beneficial because the first component 14 and the second component 16 provide structural support for the side walls of the tube 40.
  • FIG.9 is a cross-sectional side view of the high-pressure fluid handling device 10 with the tube 40 terminating at an outlet 70 at an outer surface 25 of the high-pressure fluid handling device 10, according to some embodiments.
  • the high-pressure fluid handling device 10 includes the outlet 70 positioned on an outer surface 25 of the housing 12. Furthermore, it will be readily understood by those skilled in the art that the channel 20 may originate at any face of the housing 12 and/or may terminate at any face of the housing 12, and that in some embodiments, the faces of origination and termination may be the same face. [0051] In some embodiments, the tube 40 includes a diameter d and the channel 20 includes a height (or depth) h. The height h of the channel 20 is greater than or equal to the diameter d of the tube 40. This configuration is beneficial, as the tube 40 is configured to be received within the channel 20 positioned solely on the first component 14.
  • FIG.10 is a cross-sectional side view of a multi-walled tube 80 of the high-pressure fluid handling device 11, according to some embodiments.
  • the high-pressure fluid handling device 11 includes any and/or all features of the high-pressure fluid handling device 10 described above, according to some embodiments.
  • the multi-walled tube 80 includes an interior wall 72 and an exterior wall 74, according to some embodiments.
  • the multi-walled tube 80 is fabricated from a biocompatible material such as, for example, stainless steel, titanium, poly ether-ether ketone, and combinations thereof, for example, poly-ether-ether-ketone lined stainless steel tubing.
  • a biocompatible material such as, for example, stainless steel, titanium, poly ether-ether ketone, and combinations thereof, for example, poly-ether-ether-ketone lined stainless steel tubing.
  • Other metal, metal alloy, polymeric materials, and combination materials are contemplated as being useful in the manufacture of the multi-walled tube 80 as well as coated versions of the tube 80 where a coating has been applied to one or more surfaces of the multi- walled tube 80, imparting beneficial properties, for example, chemical compatibility, bio- inertness, etc.
  • the multi- walled tube 80 may include any number of layers and/or materials.
  • an outlet frit 76 is positioned within the multi-walled tube 40 to prevent a stationary phase material Atty. Docket No.8360.002PCT1 from exiting the high-pressure handling device 10.
  • the exterior wall 74 is formed of a brazing metal filling a gap between the tube 40 and the channel 20.
  • the multi-walled tube 80 is configured to be positioned on a radiused bend 81, according to some embodiments.
  • FIGS.11A-D are cross-sectional views which show an exemplary embodiment of filling (or “packing”) a stationary phase 60 within a lumen 92, according to some embodiments.
  • FIG.11A is a cross-sectional view showing a filter 50 placed over the outlet opening 32 and secured to the housing 12 for the purpose of packing the lumen 92.
  • the filter 50 is impermeable to the stationary phase (not shown in FIG.11A), i.e., the filter 50 includes pores smaller than a particle size of the stationary phase.
  • the filter 50 is configured to allow fluid (i.e. a liquid packing slurry) to permeate through the filter 50 as the stationary phase 60 is packed and retained in the tube 90.
  • the high-pressure fluid handling device 10 includes a cavity 52 positioned adjacent to outlet 32, and between an end 96 of the tube 90.
  • FIG.11B shows a lumen 92 of the tube 90 filled with the stationary phase 60, according to some embodiments.
  • the stationary phase 60 is pressure-driven into the lumen 92 of the tube 90 through the inlet 30 (not shown in FIG.11B) and fills the lumen 42.
  • the stationary phase 60 is urged from the inlet 30 (not shown in FIG.11B) to the outlet 32, i.e., in a flow path direction as indicated by arrow 94.
  • the filter 50 and/or the block 54 positioned on the outer surface 15 of the first housing 14 enable the high packing pressure by preventing the escape of the stationary phase through the outlet 32, even under high pressure.
  • the cavity 52 is filled with the stationary phase 60.
  • the stationary phase 60 is packed into lumen 92 at a pressure between 1,500 and 20,000 psi.
  • performance improvements of HPLC and/or UHPLC may result from higher packing pressures which requires a commensurately higher pressure capability.
  • a conventional stationary phase packing may pack the stationary phase into the lumen 92 at between 1,500 and 2,000 psi.
  • stationary phase packing performed at between 10,000 and 20,000 psi may yield better separation results.
  • FIGS.12A and 12B illustrate chromatograms obtained under similar conditions through fluid handling device 10 having a tube length of 150 mm and a lumen diameter of 200 ⁇ m.
  • FIG.12A shows the results for the stationary phase packed at 1,500-2,000 psi
  • FIG.12B shows the results for the stationary phase packed at 16,500 psi.
  • the significantly higher theoretical plate counts of FIG.12A as compared to FIG.12B demonstrate the improved chromatographic performance achievable through higher stationary phase packing pressures, which are facilitated through the packing technique described herein.
  • FIG.11C shows the filter 50 removed from the outer surface 15, according to some embodiments.
  • FIG.11D shows a porous frit 62 (i.e. or porous plug) installed into the cavity 52 to retain the stationary phase 60 within the tube 90, according to some embodiments.
  • the porous frit 62 is impermeable for the stationary phase but permeable for the liquid sample and/or liquid solvent (or eluent).
  • the porous frit 62 is made from stainless steel, titanium, stainless steel-nickel alloy and/or poly ether-ether ketone.
  • FIG.13 is a flow chart of a method 1300 of forming a high-pressure fluid handling device, according to some embodiments.
  • the method 1300 includes providing a first component.
  • the first component includes any and/or all features of the first component 14 described above in any of FIGS.1-11D.
  • the method 1300 includes forming a channel into the first interface surface of the first component.
  • the channel includes any and/or all features of the channel 20 described above.
  • etching the channel 20 includes any of a variety of known techniques, including laser etching, chemical etching, lithography, CNC machining, etc.
  • Atty. Docket No.8360.002PCT1 [0061]
  • the method 1300 includes positioning a tube within the channel.
  • the tube includes any and/or all features of the tube 40 described above.
  • the tube 40 is positioned entirely within the channel 20.
  • a depth of the channel 20 is greater than or equal to an outer diameter of the tube 40 such that the tube 40 is positioned entirely within the first component 14.
  • the second interface surface 36 is substantially planar and the tube 40 does not intersect the substantially planar second interface surface 36.
  • the step 1330 includes brazing the tube 40 into the channel 20 such that gaps between the tube 40 and the channel 20 are filled with brazing metal. In some embodiments, the step 1330 includes filling the gaps between the tube 40 and the channel 20 with epoxy resin and/or other adhesive or brazing materials.
  • the method 1300 includes securing a second component having a second interface surface to the first component.
  • the second component includes any and/or all features of the second component 16 described above.
  • the first component 14 is secured to the second component 16 via the fasteners 24 and/or the alignment features 28. In some embodiments, the first component 14 is secured to the second component 16 via brazing, welding, clamping, etc.
  • the method 1300 includes packing the tube with a stationary phase medium.
  • the stationary phase medium includes any and/or all features of the stationary phase 60 described above.
  • the stationary phase 60 is packed into lumen 42 at a packing pressure of at least 1,500 psi.
  • the stationary phase 60 is packed into lumen 42 at a packing pressure of at least 2,000 psi.
  • the stationary phase 60 is packed into lumen 42 at a packing pressure of at least 5,000 psi.
  • the stationary phase 60 is packed into lumen 42 at a packing pressure of at least 10,000 psi.
  • the stationary phase 60 is packed into lumen 42 at a packing pressure of between 10,000 and 20,000 psi.
  • the term “packing pressure” means the fluid pressure driving the stationary phase 60 into lumen 42.
  • the fluid pressure is a pressure of a liquid packing slurry.
  • the liquid packing slurry may be pressurized via a pressurized gas volume.
  • performance improvements of HPLC and/or UHPLC may result from higher packing pressures which requires a commensurately higher pressure capability.
  • Atty. Docket No.8360.002PCT1 [0064]
  • FIG.14 is a flow chart of a method 1400 for packing a tube of a high-pressure fluid handling device, according to some embodiments.
  • the method 1300 includes any and/or all of the steps, features, or processes shown and described in reference to FIGS.11A-D.
  • the method 1400 includes providing a high-pressure fluid handling device.
  • the high-pressure fluid handling device includes any and/or all features of the high- pressure fluid handling device 10 described above and in FIGS.1-11D.
  • the method 1400 includes positioning a filter at an inlet and/or an outlet.
  • the inlet/outlet includes any and/or all features of the inlet 30 and the outlet 32 described above.
  • the filter (e.g., the filter 50) can be positioned on the outer surface 15 to provide an impermeable membrane for a stationary phase medium.
  • the method 1400 includes filing the tube with the stationary phase medium.
  • the stationary phase 60 is packed into lumen 42 of the tube 40 at a pressure between 1,500 and 20,000 psi.
  • performance improvements of HPLC and/or UHPLC may result from higher packing pressures which requires a commensurately higher pressure capability.
  • the method 1400 includes removing the filter from the inlet/outlet. The filter 50 can be removed from the outer surface 15 thereby exposing the inlet 30 and/or the outlet 32 to allow visual verification of whether the stationary phase 60 is present.
  • the stationary phase medium is removed from a cavity.
  • the stationary phase 60 is removed from the cavity 52 following removal of the filter 50.
  • a porous frit (or filter) is inserted into the cavity.
  • a porous frit 62 is installed into the cavity 52 to retain the stationary phase 60 within the tube 40.
  • the porous frit 62 is impermeable for the stationary phase 60 but permeable for the liquid sample and/or liquid solvent (or eluent).

Landscapes

  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Fluid Mechanics (AREA)
  • Treatment Of Liquids With Adsorbents In General (AREA)

Abstract

L'invention concerne un dispositif de manipulation de fluide haute pression. Le dispositif de manipulation de fluide haute pression comprend un boîtier, un tube et un support à phase stationnaire. Le boîtier comprend un premier composant avec une première surface d'interface et un second composant avec une seconde surface d'interface. Les premier et second composants peuvent être fixés l'un à l'autre, les première et seconde surfaces d'interface se faisant face pour former une interface entre elles. Le boîtier comprend un canal s'étendant à travers le premier composant jusqu'à l'interface et le long de celle-ci. Le tube s'étend le long du canal. Le tube définit une lumière avec une section transversale sensiblement circulaire dont le diamètre est égal ou inférieur à 1000 μm. Le support à phase stationnaire est positionné dans la lumière. Le support à phase stationnaire est conçu pour la séparation chromatographique des composés présents dans un échantillon liquide.
PCT/US2024/027435 2023-05-02 2024-05-02 Dispositif de manipulation de fluide haute pression pour chromatographie en phase liquide Pending WO2024229239A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202363463413P 2023-05-02 2023-05-02
US63/463,413 2023-05-02

Publications (1)

Publication Number Publication Date
WO2024229239A1 true WO2024229239A1 (fr) 2024-11-07

Family

ID=93333463

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2024/027435 Pending WO2024229239A1 (fr) 2023-05-02 2024-05-02 Dispositif de manipulation de fluide haute pression pour chromatographie en phase liquide

Country Status (1)

Country Link
WO (1) WO2024229239A1 (fr)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4068528A (en) * 1976-01-19 1978-01-17 Rheodyne Incorporated Two position rotary valve for injecting sample liquids into an analysis system
US20070029241A1 (en) * 2005-08-03 2007-02-08 Agilent Technologies, Inc. Column for liquid chromatography with adjustable compression
US20180161697A1 (en) * 2016-12-09 2018-06-14 Idex Health & Science Llc High Pressure Valve With Two-Piece Stator Assembly
US20200292108A1 (en) * 2014-10-23 2020-09-17 Idex Health & Science Llc Face-Sealing Fluidic Connection System
US20210062133A1 (en) * 2019-08-28 2021-03-04 Nirrin Technologies, Inc. Device and bioreactor monitoring system and method

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4068528A (en) * 1976-01-19 1978-01-17 Rheodyne Incorporated Two position rotary valve for injecting sample liquids into an analysis system
US20070029241A1 (en) * 2005-08-03 2007-02-08 Agilent Technologies, Inc. Column for liquid chromatography with adjustable compression
US20200292108A1 (en) * 2014-10-23 2020-09-17 Idex Health & Science Llc Face-Sealing Fluidic Connection System
US20180161697A1 (en) * 2016-12-09 2018-06-14 Idex Health & Science Llc High Pressure Valve With Two-Piece Stator Assembly
US20210062133A1 (en) * 2019-08-28 2021-03-04 Nirrin Technologies, Inc. Device and bioreactor monitoring system and method

Similar Documents

Publication Publication Date Title
US6993958B2 (en) Capillary column chromatography process and system
US8323488B2 (en) IC-processed polymer nano-liquid chromatoraphy system on-a-chip and method of making it
US6936167B2 (en) System and method for performing multiple parallel chromatographic separations
JP6882480B2 (ja) 多部品ステータアセンブリを伴う高圧弁
US11353132B2 (en) High pressure valve with multi-piece stator assembly
US9671048B2 (en) Manifold connection assembly
EP2969460B1 (fr) Raccord à renfort structurel et passage de fluide biocompatible
JP2015516563A (ja) 接続組立体
US9724621B2 (en) Device, apparatus and method for performing separations
US9791080B2 (en) Microfluidic interconnect
WO2009146290A1 (fr) Dispositif et procédé pour raccorder des conduits de fluide
JP4909897B2 (ja) 分離を実施するデバイス、方法、および装置
WO2024229239A1 (fr) Dispositif de manipulation de fluide haute pression pour chromatographie en phase liquide
US6966336B1 (en) Fluid injection microvalve
EP3856383B1 (fr) Colonne comprenant un ensemble limité par compression
EP3561504B1 (fr) Soupape haute pression comportant un ensemble stator multi-pièces
WO2004042383A1 (fr) Systeme et procede de realisation de nombreuses separations chromatographiques paralleles
Renzi Fluid injection microvalve

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 24800589

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 2024800589

Country of ref document: EP