Liquid Chromatography Technology

By using coated metal fluid contact elements in liquid chromatography systems, combined with high temperature and high pressure conditions, the problem of incompatibility of traditional materials under certain conditions is solved, achieving a wider range of applications and higher analytical efficiency.

JP7676495B2Active Publication Date: 2025-05-14SILCOTEK CORP
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Patent Information

Application Number
JP2023166219
Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
Priority Date
2018-02-23
Filing Date
2023-09-27
Publication Date
2025-05-14
Estimated Expiration
2039-02-22

AI Technical Summary

Technical Problem

In existing liquid chromatography techniques, materials used such as titanium and polyether ether ketones (PEEK) are not compatible under certain conditions, limiting the application range and efficiency of liquid chromatography.

Method used

The compatibility limitations of traditional materials are overcome by using coated metal fluid contact elements in liquid chromatography systems, combining high temperature and high pressure conditions, to process fluids containing protein analytes or chelating agents.

Benefits of technology

It realizes the treatment of fluids incompatible with traditional materials under high temperature and high pressure conditions, expands the application range of liquid chromatography technology, and improves the accuracy and efficiency of analysis.

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Abstract

To provide quick, compact, precise and cost-effective LC techniques.SOLUTION: An LC technique disclosed herein comprises preparing a liquid chromatography system having a coated metallic fluid-contacting element, and transporting a fluid to contact the coated metallic fluid-contacting element. Conditions for the transporting of the fluid are selected from a group consisting of the followings: temperature of the fluid is greater than 150°C; pressure urging the fluid is greater than 60 MPa; the fluid contains a protein-containing analyte incompatible with one of titanium and polyether ether ketone; and the fluid contains a chelating agent incompatible with one or both of the titanium or the polyether ether ketone.SELECTED DRAWING: Figure 2
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Description

[Technical field]

[0001]

[0001] The present invention is directed to the art of liquid chromatography, and more particularly to liquid chromatography utilizing coated metallic fluid contacting elements. [Background technology]

[0002]

[0002] Analytical instruments are a field in constant evolution. There is a constant demand to make them faster, smaller, more precise and more accurate. However, these demands are subject to limitations that are not physically possible with existing materials.

[0003]

[0003] For example, titanium is used in high performance (or high pressure) liquid chromatography (HPLC). However, under certain conditions, titanium is resistant to ammonia, chlorine (both wet and dry), HCl, nitrating acid (a combination of nitric and sulfuric acids), phosphoric acid, sodium and potassium hydroxides, bleach, and sulfuric acid. Titanium is also brittle, limiting the ability to bend it, for example, into tubes. Titanium is also very expensive, making it unavailable for cost-effective technology.

[0004]

[0004] In contrast, polyetheretherketone (PEEK) is flexible and inexpensive. However, PEEK has many other drawbacks. Under certain conditions, PEEK is incompatible with benzenesulfonic acid, chlorine (both wet and dry), nitric acid, sulfuric acid, carbolic acid, ultraviolet light, methylene chloride, dimethyl sulfate, tetrahydrofuran, and other organic solvents. PEEK also has an upper temperature limit of 100°C to 143°C, depending on the application. Summary of the Invention [Problem to be solved by the invention]

[0005]

[0005] Liquid chromatography techniques, systems, and components that exhibit one or more improvements over the prior art would be desirable in the art. [Means for solving the problem]

[0006] In one embodiment, the liquid chromatography technique includes providing a liquid chromatography system with a coated metal fluid contact element, and transporting a fluid to contact the coated metal fluid contact element, the conditions of the step of transporting the fluid being selected from the group consisting of a temperature of the fluid greater than 150° C., a pressure driving the fluid greater than 60 MPa, the fluid having a protein-containing analyte that is incompatible with one or both of titanium and polyetheretherketone, the fluid having a chelating agent that is incompatible with one or both of titanium and polyetheretherketone, and combinations thereof.

[0007] In another embodiment, the liquid chromatography technique includes providing a liquid chromatography system including a coated metal column, a degasser, a sample, one or more pumps, and a detector. The liquid chromatography technique further includes transporting a fluid through the coated metal column, the conditions of the step of transporting the fluid including one or both of the fluid having a protein-containing analyte incompatible with one or both of titanium and polyetheretherketone, and the fluid having a chelating agent incompatible with one or both of titanium or polyetheretherketone.

[0008] In another embodiment, the liquid chromatography technique includes providing a liquid chromatography system including a coated metal column, the stationary phase being a coated metal column. The liquid chromatography technique further includes a step of transporting a fluid through the coated metal column, the conditions of the step of transporting the fluid include a temperature of the fluid greater than 150° C., a pressure driving the fluid through the coated metal column greater than 60 MPa, the fluid having a protein-containing analyte incompatible with one or both of titanium and polyetheretherketone, the fluid having a chelating agent incompatible with one or both of titanium and polyetheretherketone, and combinations thereof. The coated metal column has a coating comprising carbon, silicon, oxygen, and hydrogen, and a stainless steel substrate, the pH of the fluid is less than 2, the coated metal column has a diameter of less than 2.1 mm, the coated metal column has a length of less than 20 cm, and the coated metal component has a coating having a thickness of at least 400 nm. The step of transporting the fluid through the coated metal column is at a linear velocity of at least 8 mm per second. The fluid includes a solvent selected from the group consisting of water, acetonitrile, methanol, formic acid, phosphoric acid, tetrahydrofuran, trifluoroacetic acid, and combinations thereof.The fluid includes an analyte selected from the group consisting of tetracycline, N-hydroxypyridin-2-one, adenosine triphosphate, and deoxynucleotide monophosphate.

[0009] Other features and advantages of the present invention will become apparent from the following more detailed description, taken in conjunction with the accompanying drawings, which illustrate, by way of example, the principles of the invention. [Brief description of the drawings]

[0010] [Figure 1] FIG. 1 is a schematic diagram of a liquid chromatography system for practicing one embodiment of the liquid chromatography technique described in this disclosure. [Diagram 2]

[0011] FIG. 1 is a schematic perspective view of a column for a liquid chromatography system capable of implementing one embodiment of the liquid chromatography technique described in this disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011]

[0012] Wherever possible, the same reference numbers will be used throughout the drawings to refer to the same parts.

[0013] Liquid chromatography techniques, systems, and components are provided. The disclosed embodiments extend the capabilities of liquid chromatography, allow for increasing the accuracy of liquid chromatography, allow for increasing the precision of liquid chromatography, allow for reducing the size of columns used in liquid chromatography, allow for shortening the analysis time of liquid chromatography, allow for bioinert and / or protein anti-stiction operation of liquid chromatography, and allow for the inability to react with titanium-incompatible fluids under certain conditions (e.g., ammonia, chlorine (both wet and dry), HCl, nitrating acid (a combination of nitric acid and sulfuric acid), phosphoric acid, hydroxide, etc.), for example, as compared to concepts that may not include one or more of the features disclosed herein. sodium and potassium hydroxide, bleach, and sulfuric acid), allow operation with fluids that are incompatible with polyetheretherketone (e.g., benzenesulfonic acid, chlorine (both wet and dry), nitric acid, sulfuric acid, phenol, ultraviolet light, methylene chloride, dimethyl sulfate, tetrahydrofuran, and other organic solvents), allow liquid chromatography to be performed at higher pressures, allow liquid chromatography to be performed at higher temperatures, allow liquid chromatography to be performed with smaller particles in the stationary phase, allow liquid chromatography to be performed with columns of smaller diameter and / or length, or combinations thereof.

[0012]

[0014] 1, liquid chromatography techniques are disclosed utilizing a liquid chromatography system 100. It will be appreciated by those skilled in the art that liquid chromatography techniques may be used with any suitable configuration of liquid chromatography system 100. Such suitable configurations include, but are not limited to, high performance (or high pressure) liquid chromatography (HPLC), ultra performance (or high pressure) liquid chromatography (UHPLC), partition HPLC or partition UHPLC, normal phase chromatography, displacement chromatography, reverse phase chromatography, size exclusion chromatography, ion exchange chromatography, or combinations thereof.

[0013]

[0015] 1, an exemplary system 100 includes a solvent reservoir 101, a solvent degasser 102, a gradient valve 103, a mixing vessel 104 for delivering the mobile phase, a high pressure pump 105, a switching valve 106 at the injection or loading position, a sample injection loop 107, a pre-column section 108, a coated metal column 109, a detector 110 (e.g., an infrared or ultraviolet detector), a data acquisition system 111 (e.g., a computer), and a waste or fraction collector 112. Any additional or alternative components can be used, so long as the system 100 includes a coated metal fluid contacting element, such as a coated metal column 109, or any other component of the system 100 that contacts a fluid, e.g., a mobile phase, a solvent, an analyte, or a combination thereof. Additionally or alternatively, other components, e.g., frits, fittings, heads, valves, tubing, vessels, or combinations thereof, can be similarly coated.

[0014]

[0016] Referring to FIG. 2, in one embodiment, the coated metal column 109 contains particles 205 or beads. The particles 205 function as a stationary phase during liquid chromatography techniques. The particles 205 have a particle size (e.g., diameter and / or width) that is less than 10 micrometers, less than 6 micrometers, less than 5 micrometers, less than 3 micrometers, less than 2 micrometers, less than 1.7 micrometers, less than 1.5 micrometers, between 1 micrometer and 10 micrometers, between 1 micrometer and 5 micrometers, between 1 micrometer and 3 micrometers, between 1 micrometer and 2 micrometers, 0.67 micrometers, less than 0.67 micrometers, or any suitable combination, subcombination, range, or subrange thereof. In one embodiment, the particles 205 are hydrophobic and / or porous. The coating 203 on the coated metal column 109 allows the particles 205 having these dimensions and characteristics to be used during liquid chromatography techniques. Suitable thicknesses of the coating 203 include, but are not limited to, at least 50 nm, at least 100 nm, at least 200 nm, at least 300 nm, at least 400 nm, at least 600 nm, at least 800 nm, at least 1,000 nm, at least 1,200 nm, between 50 nm and 1,600 nm, between 400 nm and 1,600 nm, between 1,000 nm and 1,600 nm, or any suitable combination, subcombination, range, or sub-range thereof.

[0015]

[0017] Suitable lengths for the coated metal column 109 include, but are not limited to, 10 cm to 20 cm, 10 cm to 50 cm, 15 cm, greater than 10 cm, greater than 14 cm, less than 20 cm, less than 16 cm, 10 cm to 400 cm, 10 cm to 100 cm, greater than 100 cm, greater than 250 cm, or any suitable combination, subcombination, range, or sub-range thereof.

[0016]

[0018] Suitable diameters (or widths) of the coated metal column 109 include, but are not limited to, less than 2.1 mm, less than 1.7 cm, less than 1.5 cm, less than 0.3 mm, or any suitable combination, subcombination, range, or sub-range thereof.

[0017]

[0019] The coated metal column 109 includes a substrate 201 and a coating 203. The substrate 201 is a metallic material, for example, stainless steel. Suitable stainless steels include 304 stainless steel and 316 stainless steel. Any other metallic material compatible with the operating conditions of liquid chromatography techniques is suitable. Suitable metallic materials include, but are not limited to, iron. The alloys may be selected from the group consisting of ferrous alloys, non-ferrous alloys, nickel-based alloys, stainless steels (martensitic or austenitic), aluminum alloys, composite metals, or combinations thereof.

[0018]

[0020] In one embodiment, the metallic material is or includes, by weight, the following composition: 0.08% or less carbon, 18%-20% chromium, 2% or less manganese, 8%-10.5% nickel, 0.045% or less phosphorus, 0.03% or less sulfur, 1% or less silicon, and the balance iron (e.g., 66%-74% iron).

[0019]

[0021] In one embodiment, the metallic material is or includes, by weight, the following composition: 0.08% or less carbon, 2% or less manganese, 0.045% or less phosphorus, 0.03% or less sulfur, 0.75% or less silicon, 16%-18% chromium, 10%-14% nickel, 2%-3% molybdenum, 0.1% or less nitrogen, and the balance iron.

[0020]

[0022] In one embodiment, the metallic material is or includes, by weight, the following composition: 0.03% or less carbon, 2% or less manganese, 0.045% or less phosphorus, 0.03% or less sulfur, 0.75% or less silicon, 16%-18% chromium, 10%-14% nickel, 2%-3% molybdenum, 0.1% or less nitrogen, and the balance iron.

[0021]

[0023] In one embodiment, the metallic material is or includes, by weight, the following composition: 14%-17% chromium, 6%-10% iron, 0.5%-1.5% manganese, 0.1%-1% copper, 0.1%-1% silicon, 0.01%-0.2% carbon, 0.001%-0.2% sulfur, and the balance nickel (e.g., 72%).

[0022]

[0024] In one embodiment, the metallic material is or includes, by weight, the following composition: 20%-24% chromium, 1%-5% iron, 8%-10% molybdenum, 10%-15% cobalt, 0.1%-1% manganese, 0.1%-1% copper, 0.8%-1.5% aluminum, 0.1%-1% titanium, 0.1%-1% silicon, 0.01%-0.2% carbon, 0.001%-0.2% sulfur, 0.001%-0.2% phosphorus, 0.001%-0.2% boron, and the balance nickel (e.g., 44.2%-56%).

[0023]

[0025] In one embodiment, the metallic material is or includes, by weight, the following composition: 20%-23% chromium, 4%-6% iron, 8%-10% molybdenum, 3%-4.5% niobium, 0.5%-1.5% cobalt, 0.1%-1% manganese, 0.1%-1% aluminum, 0.1%-1% titanium, 0.1%-1% silicon, 0.01%-0.5% carbon, 0.001%-0.02% sulfur, 0.001%-0.02% phosphorus, and the balance nickel (e.g., 58%).

[0024]

[0026] In one embodiment, the metallic material is or includes, by weight, the following composition: 25%-35% chromium, 8%-10% iron, 0.2%-0.5% manganese, 0.005%-0.02% copper, 0.01%-0.03% aluminum, 0.3%-0.4% silicon, 0.005%-0.03% carbon, 0.001%-0.005% sulfur, and the balance nickel (e.g., 59.5%).

[0025]

[0027] In one embodiment, the metallic material is or includes, by weight, the following composition: 17%-21% chromium, 2.8%-3.3% iron, 4.75%-5.5% niobium, 0.5%-1.5% cobalt, 0.1%-0.5% manganese, 0.2%-0.8% copper, 0.65%-1.15% aluminum, 0.2%-0.4% titanium, 0.3%-0.4% silicon, 0.01%-1% carbon, 0.001-0.02% sulfur, 0.001-0.02% phosphorus, 0.001-0.02% boron, and the balance nickel (e.g., 50%-55%).

[0026]

[0028] In one embodiment, the metallic material is or includes, by weight, 2%-3% cobalt, 15%-17% chromium, 5%-17% molybdenum, 3%-5% tungsten, 4%-6% iron, 0.5%-1% silicon, 0.5%-1.5% manganese, 0.005-0.02% carbon, 0.3%-0.4% vanadium, and the balance nickel.

[0027]

[0029] In one embodiment, the metallic material is or includes, by weight, the following composition: 0.15% or less carbon, 3.5%-5.5% tungsten, 4.5%-7% iron, 15.5%-17.5% chromium, 16%-18% molybdenum, 0.2%-0.4% vanadium, 1% or less manganese, 1% or less sulfur, 1% or less silicon, 0.04% or less phosphorus, 0.03% or less sulfur, and the balance nickel.

[0028]

[0030] In one embodiment, the metallic material is or includes, by weight, the following composition: cobalt 2.5% or less, chromium 22% or less, molybdenum 13% or less, tungsten 3% or less, iron 3% or less, silicon 0.08% or less, manganese 0.5% or less, carbon 0.01% or less, vanadium 0.35% or less, and the balance nickel (e.g., 56%).

[0029]

[0031] In one embodiment, the metallic material is or includes, by weight, 1%-2% cobalt, 20%-22% chromium, 8%-10% molybdenum, 0.1%-1% tungsten, 17%-20% iron, 0.1%-1% silicon, 0.1%-1% manganese, 0.05-0.2% carbon, and the balance nickel.

[0030]

[0032] In one embodiment, the metallic material is or includes, by weight, 0.01%-0.05% boron, 0.01%-0.1% chromium, 0.003%-0.35% copper, 0.005%-0.03% gallium, 0.006%-0.8% iron, 0.006%-0.3% magnesium, 0.02%-1% silicon+iron, 0.006%-0.35% silicon, 0.002%-0.2% titanium, 0.01%-0.03% vanadium+titanium, 0.005%-0.05% vanadium, 0.006%-0.1% zinc, and the balance aluminum (e.g., greater than 99%).

[0031]

[0033] In one embodiment, the metallic material is or includes, by weight, the following composition: 0.05%-0.4% chromium, 0.03%-0.9% copper, 0.05%-1% iron, 0.05%-1.5% magnesium, 0.5%-1.8% manganese, 0.5%-0.1% nickel, 0.03%-0.35% titanium, up to 0.5% vanadium, 0.04%-1.3% zinc, and the balance aluminum (e.g., 94.3%-99.8%).

[0032]

[0034] In one embodiment, the metallic material is or includes, by weight, the following composition: 0.0003%-0.07% beryllium, 0.02%-2% bismuth, 0.01%-0.25% chromium, 0.03%-5% copper, 0.09%-5.4% iron, 0.01%-2% magnesium, 0.03%-1.5% manganese, 0.15%-2.2% nickel, 0.6%-21.5% silicon, 0.005%-0.2% titanium, 0.05%-10.7% zinc, and the balance aluminum (e.g., 70.7%-98.7%).

[0033]

[0035] In one embodiment, the metallic material is, by weight, 0.15%-1.5% bismuth, 0.003%-0.06% boron, 0.03%-0.4% chromium, 0.01%-1.2% copper, 0.12%-0.5% chromium + manganese, 0.04%-1% iron, 0.003%-2% lead, 0.2%-3% magnesium, 0.02%-1.4% manganese, 0.05%-0.05% nickel. 2%, oxygen 0.5%-0.5%, silicon 0.2%-1.8%, strontium 0.05% or less, tin 0.05%-2%, titanium 0.01%-0.25%, vanadium 0.05%-0.3%, zinc 0.03%-2.4%, zirconium 0.05%-0.2%, zirconium + titanium 0.150-0.2%, and the balance is aluminum (e.g., 91.7% ~99.6%) of the composition or containing the same.

[0034]

[0036] In one embodiment, the metallic material is or includes, by weight, 0.4%-0.8% silicon, 0.7% or less iron, 0.15%-0.4% copper, 0.15% or less manganese, 0.8%-1.2% magnesium, 0.04%-0.35% chromium, 0.25% or less zinc, 0.15% or less titanium, optional, incidental impurities (e.g., less than 0.05% each and less than 0.15% together), and the balance aluminum (e.g., 95%-98.6%).

[0035]

[0037] In one embodiment, the metallic material is or includes, by weight, 11%-13% silicon, 0.6% or less impurities / residuals, and the balance aluminum.

[0038] The coating 203 includes one or more of deposition, decomposition, functionalization, oxidation, or a combination thereof. In one embodiment, the coating 203 includes carbon, silicon, oxygen, and hydrogen. In additional or alternative embodiments, other components of the coating 203 include, but are not limited to, fluorine, nitrogen, decomposition products from precursor materials, functionalization from precursor materials, or combinations thereof. Suitable precursor materials include, but are not limited to, silane, silane and ethylene, silane and an oxidizer, dimethylsilane, dimethylsilane and an oxidizer, trimethylsilane, trimethylsilane and an oxidizer, dialkylsilyl dihydrides, alkylsilyl trihydrides, non-pyrophoric species (e.g., dialkylsilyl dihydrides and / or alkylsilyl trihydrides), heat reactive materials (e.g., carbosilanes and / or carboxysilanes, e.g., amorphous carbosilanes and / or amorphous carboxysilanes), carbosilyl recombinable species (disilyl or trisilyl fragments), methyltrimethoxysilane, methyltriethoxysilane, dimethyldimethoxysilane, dimethyldiethoxysilane, trimethylmethoxysilane, trimethylethoxysilane, ammonia, hydrazine, trisilylamine, bisilylamine, bis(phenylene oxide), ... bis(tert-butylamino)silane, 1,2-bis(dimethylamino)tetramethyldisilane, dichlorosilane, hexachlorodisilane, organofluorotrialkoxysilane, organofluorosilyl hydride, organofluorosilyl, fluorinated alkoxysilane, fluoroalkylsilane, fluorosilane, tridecafluoro 1,1,2,2-tetrahydrooctylsilane, (tridecafluoro-1,1,2,2-tetrahydrooctyl)triethoxysilane, triethoxy(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1-octyl)silane, (perfluorohexylethyl)triethoxysilane, (3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecyl)trimethoxysilane, or combinations thereof.

[0036]

[0039] Liquid chromatography techniques include a fluid being transported through a coated metal column 109, for example, past particles 205 that function as the stationary phase of the liquid chromatography technique. The fluid is or includes a mobile phase, one or more solvents, one or more analytes, or a combination thereof. Suitable fluid species include, but are not limited to, protein-containing analytes incompatible with one or both of titanium and polyetheretherketone, and chelating agents incompatible with one or both of titanium or polyetheretherketone. Specific solvents that can be used within liquid chromatography techniques include, but are not limited to, water, acetonitrile, methanol, formic acid, phosphoric acid, tetrahydrofuran, trifluoroacetic acid, and combinations thereof. Specific analytes that can be used within liquid chromatography techniques include, but are not limited to, tetracycline, N-hydroxypyridin-2-one, adenosine triphosphate, and deoxynucleotide monophosphate.

[0037]

[0040] In one embodiment, the liquid chromatography technique is used in conjunction with other operating parameters of the liquid chromatography technique to determine whether the fluid is, for example, polyetheretherketone and / or temperatures that are not suitable for titanium, including, but not limited to, 100° C.-200° C., 200° C.-300° C., 300° C.-400° C., 400° C.-450° C., greater than 150° C., greater than 200° C., greater than 250° C., greater than 300° C., greater than 350° C., greater than 400° C., or any suitable combination, subcombination, range, or sub-range thereof.

[0038]

[0041] In one embodiment, the liquid chromatography technique, in conjunction with other operating parameters of the liquid chromatography technique, includes urging the fluid at a pressure that is not suitable for, for example, polyetheretherketone and / or titanium, including, but not limited to, 10 MPa to 150 MPa, 30 MPa to 150 MPa, 50 MPa to 100 MPa, 100 MPa to 150 MPa, 100 MPa to 200 MPa, or any suitable combination, subcombination, range, or sub-range thereof.

[0039]

[0042] In one embodiment, the liquid chromatography technique, in conjunction with other operating parameters of the liquid chromatography technique, includes that the fluid is at a pH value that is inappropriate for, for example, polyetheretherketone and / or titanium, including, but not limited to, less than 3, less than 2, less than 1, greater than 9, greater than 10, greater than 12, 0-3, 9-14, 0-14, or any suitable combination, subcombination, range, or sub-range thereof.

[0040]

[0043] In one embodiment, the liquid chromatography technique, in conjunction with other operating parameters of the liquid chromatography technique, includes transporting a fluid at a linear velocity that is incompatible with, for example, polyetheretherketone and / or titanium, including, but not limited to, 1-9 mm per second, 3-9 mm per second, at least 3 mm per second, at least 8 mm per second, or any suitable combination, subcombination, range, or sub-range thereof.

[0041]

[0044] Although the present invention has been described with reference to one or more embodiments, it will be understood by those skilled in the art that various modifications can be made and equivalents can be substituted for elements of the present invention without departing from the scope of the invention. In addition, many modifications can be made to adapt a particular situation or material to the teachings of the invention without departing from the essential scope of the invention. Therefore, it is intended that the present invention not be limited to the particular embodiment disclosed as the best mode contemplated for carrying out the invention, but that the present invention will include all embodiments that fall within the scope of the appended claims. Furthermore, all numerical values ​​specified in the detailed description should be construed as if both precise values ​​and approximations were explicitly specified.

[0042] [Mode of the invention] [1] Providing a liquid chromatography system comprising a coated metal fluid contact element; Transporting the fluid to contact the coated metallic fluid contact element A liquid chromatography technique comprising: The conditions for transporting the fluid are selected from the group consisting of: a temperature of the fluid greater than 150° C.; a pressure driving the fluid greater than 60 MPa; the fluid having a protein-containing analyte that is incompatible with one or both of titanium and polyetheretherketone; the fluid having a chelating agent that is incompatible with one or both of titanium or polyetheretherketone; and combinations thereof. Liquid chromatography techniques. [2] 2. The liquid chromatography technique described in 1, wherein the coated metal fluid contacting element has a coating comprising carbon, silicon, oxygen, and hydrogen, and a stainless steel substrate. [3] 2. The liquid chromatography technique described in 1, wherein the coated metal fluid contacting element has a coating comprising carbon, silicon, oxygen, hydrogen, and fluorine, and a stainless steel substrate. [4] 2. The liquid chromatography technique described in 1, wherein the coated metal fluid contacting element has a coating comprising carbon, silicon, oxygen, hydrogen, and nitrogen, and a stainless steel substrate. [5] 2. The technology described in 1, wherein the pressure driving the fluid is greater than 120 MPa. [6] 2. The technique described in claim 1, wherein the temperature of the fluid is greater than 400° C. [7] 2. The technique of claim 1, wherein the pH of the fluid is less than 2. [8] 2. The technique described in 1, wherein the coated metal fluid contact element is a coated metal column having a diameter of less than 2.1 mm. [9] 2. The technique of claim 1, wherein the coated metal fluid contact element has a length of less than 20 cm.

[10] 2. The technique of claim 1, wherein the step of transporting the fluid through the coated metallic fluid contact element has a linear velocity of at least 8 mm per second.

[11] 2. The technique of claim 1, wherein the fluid comprises a solvent selected from the group consisting of water, acetonitrile, methanol, formic acid, phosphoric acid, tetrahydrofuran, trifluoroacetic acid, and combinations thereof.

[12] 2. The technique of claim 1, wherein the fluid comprises an analyte selected from the group consisting of tetracycline, N-hydroxypyridin-2-one, adenosine triphosphate, and deoxynucleotide monophosphate.

[13] 2. The technique described in 1, wherein the liquid chromatography system comprises a stationary phase disposed within a coated metal fluid contacting element, the stationary phase comprising particles having a particle size of less than 3 micrometers, and the coated metal column has a length of 10 cm to 20 cm.

[14] A liquid chromatography system comprising a stationary phase disposed within a coated metal fluid contact element, the stationary phase comprising particles having a particle size of less than 1.5 micrometers. The described technology.

[15] 2. The technique described in claim 1, wherein the coated metal part is bioinert.

[16] 2. The technique described in 1, wherein the coated metal fluid contact element is resistant to protein stiction.

[17] 2. The technique of claim 1, wherein the coated metallic fluid contact element has a coating having a thickness of at least 400 nm.

[18] 2. The technique described in 1, wherein the coated metal fluid contact element has a coating having a thickness of 1,000 nm to 1,600 nm.

[19] providing a liquid chromatography system including a coated metal column, a degasser, a sample, one or more pumps, and a detector; transporting a fluid through the coated metal column, wherein the conditions for transporting the fluid include one or both of the fluid having a protein-containing analyte that is incompatible with one or both of titanium and polyetheretherketone, and the fluid having a chelating agent that is incompatible with one or both of titanium or polyetheretherketone. Liquid chromatography techniques, including:

[20] Providing a liquid chromatography system comprising a coated metal column, wherein a stationary phase is disposed within the coated metal column, the stationary phase comprising particles having a particle size of less than 1.5 micrometers; transporting a fluid through the coated metal column, wherein the conditions of the step of transporting the fluid include a temperature of the fluid greater than 150° C., a pressure driving the fluid through the coated metal column greater than 60 MPa, the fluid having a protein-containing analyte that is incompatible with one or both of titanium and polyetheretherketone, the fluid comprising a chelating agent that is incompatible with one or both of titanium or polyetheretherketone, and combinations thereof. A liquid chromatography technique comprising: the coated metal column comprises a coating comprising carbon, silicon, oxygen, and hydrogen, and a stainless steel substrate, the pH of the fluid is less than 2, the coated metal column has a diameter of less than 2.1 mm, the coated metal column has a length of less than 20 cm, and the coated metal part has a coating having a thickness of at least 400 nm; Transporting the fluid through the coated metal column is at a linear velocity of at least 8 mm per second; the fluid comprises a solvent selected from the group consisting of water, acetonitrile, methanol, formic acid, phosphoric acid, tetrahydrofuran, trifluoroacetic acid, and combinations thereof; the fluid comprises an analyte selected from the group consisting of tetracycline, N-hydroxypyridin-2-one, adenosine triphosphate, and deoxynucleotide monophosphate; Liquid chromatography techniques.

Claims

1. Providing a liquid chromatography system comprising a coated metal fluid contact element, the coated metal fluid contact element having a coating comprising carbon, silicon, oxygen and hydrogen and a stainless steel substrate; and Transporting a fluid to contact the coated metallic fluid contact element.

1. A method of using a liquid chromatography system comprising: The conditions for transporting the fluid are: the fluid has a protein-containing analyte that is incompatible with one or both of titanium and polyetheretherketone; and The fluid has a chelating agent that is incompatible with either or both of titanium and polyetheretherketone. including one or both of the fluid comprises an analyte selected from the group consisting of tetracycline, N-hydroxypyridin-2-one, adenosine triphosphate and deoxynucleotide monophosphate; The above method.

2. The method of claim 1 , wherein the coated metallic fluid contact element has a coating comprising carbon, silicon, oxygen, hydrogen, and fluorine, and a stainless steel substrate.

3. The method of claim 1 , wherein the coated metallic fluid contact element has a coating comprising carbon, silicon, oxygen, hydrogen, and nitrogen, and a stainless steel substrate.

4. 2. The method of claim 1, wherein the pressure driving the fluid is greater than 120 MPa.

5. The method of claim 1 , wherein the temperature of the fluid is greater than 400° C.

6. The method of claim 1 , wherein the pH of the fluid is less than 2.

7. 2. The method of claim 1, wherein the coated metal fluid contact element is a coated metal column having a diameter of less than 2.1 mm.

8. The method of claim 1 , wherein the coated metallic fluid contact element has a length of less than 20 cm.

9. 10. The method of claim 1, wherein the step of transporting the fluid through the coated metallic fluid contact element has a linear velocity of at least 8 mm per second.

10. 10. The method of claim 1, wherein the fluid comprises a solvent selected from the group consisting of water, acetonitrile, methanol, formic acid, phosphoric acid, tetrahydrofuran, trifluoroacetic acid, and combinations thereof.

11. 2. The method of claim 1, wherein the liquid chromatography system comprises a stationary phase disposed within the coated metal fluid contact element, the stationary phase comprising particles having a particle size of less than 3 micrometers, the coated metal fluid contact element being a coated metal column, and the coated metal column having a length of 10 cm to 20 cm.

12. 10. The method of claim 1, wherein the liquid chromatography system comprises a stationary phase disposed within the coated metal fluid contact element, the stationary phase comprising particles having a particle size of less than 1.5 micrometers.

13. The method of claim 1 , wherein the coated metallic fluid contact element is bioinert.

14. The method of claim 1 , wherein the coated metallic fluid contact element is resistant to protein stiction.

15. The method of claim 1 , wherein the coated metallic fluid contact element has a coating having a thickness of at least 400 nm.

16. The method of claim 1, wherein the coated metallic fluid contact element has a coating having a thickness of from 1,000 nm to 1,600 nm.

Citation Information

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