WO2025038294A1 - Capillary ampules and capillary ampule systems - Google Patents
Capillary ampules and capillary ampule systems Download PDFInfo
- Publication number
- WO2025038294A1 WO2025038294A1 PCT/US2024/040577 US2024040577W WO2025038294A1 WO 2025038294 A1 WO2025038294 A1 WO 2025038294A1 US 2024040577 W US2024040577 W US 2024040577W WO 2025038294 A1 WO2025038294 A1 WO 2025038294A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- capillary
- volume
- ampule
- liquid volume
- liquid
- Prior art date
Links
- 239000003708 ampul Substances 0.000 title claims abstract description 250
- 239000007788 liquid Substances 0.000 claims abstract description 262
- 230000004888 barrier function Effects 0.000 claims description 44
- 239000012925 reference material Substances 0.000 claims description 40
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 33
- 239000000463 material Substances 0.000 claims description 24
- 239000005350 fused silica glass Substances 0.000 claims description 17
- 238000000926 separation method Methods 0.000 claims description 12
- 239000002184 metal Substances 0.000 claims description 5
- 229920000642 polymer Polymers 0.000 claims description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 33
- 150000001875 compounds Chemical class 0.000 description 32
- 239000007789 gas Substances 0.000 description 28
- 239000011521 glass Substances 0.000 description 23
- 239000000243 solution Substances 0.000 description 23
- 239000002904 solvent Substances 0.000 description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 17
- 229910052757 nitrogen Inorganic materials 0.000 description 16
- 239000000126 substance Substances 0.000 description 16
- 239000003153 chemical reaction reagent Substances 0.000 description 14
- 238000000576 coating method Methods 0.000 description 13
- 238000011049 filling Methods 0.000 description 13
- 238000011068 loading method Methods 0.000 description 13
- 239000011248 coating agent Substances 0.000 description 11
- 238000000034 method Methods 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 239000012530 fluid Substances 0.000 description 9
- 238000002347 injection Methods 0.000 description 9
- 239000007924 injection Substances 0.000 description 9
- 230000014759 maintenance of location Effects 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- 239000000377 silicon dioxide Substances 0.000 description 8
- 238000003860 storage Methods 0.000 description 8
- 230000009849 deactivation Effects 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 238000001179 sorption measurement Methods 0.000 description 7
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- -1 but not limited to Substances 0.000 description 6
- 229910000077 silane Inorganic materials 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 238000012546 transfer Methods 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 5
- 239000004810 polytetrafluoroethylene Substances 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 238000004891 communication Methods 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 239000011261 inert gas Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- LIKFHECYJZWXFJ-UHFFFAOYSA-N dimethyldichlorosilane Chemical compound C[Si](C)(Cl)Cl LIKFHECYJZWXFJ-UHFFFAOYSA-N 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 238000007789 sealing Methods 0.000 description 3
- OBAJXDYVZBHCGT-UHFFFAOYSA-N tris(pentafluorophenyl)borane Chemical compound FC1=C(F)C(F)=C(F)C(F)=C1B(C=1C(=C(F)C(F)=C(F)C=1F)F)C1=C(F)C(F)=C(F)C(F)=C1F OBAJXDYVZBHCGT-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 239000004593 Epoxy Substances 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 238000000231 atomic layer deposition Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000000769 gas chromatography-flame ionisation detection Methods 0.000 description 2
- 239000001307 helium Substances 0.000 description 2
- 229910052734 helium Inorganic materials 0.000 description 2
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 229920000647 polyepoxide Polymers 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000010926 purge Methods 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000012086 standard solution Substances 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- RBTBFTRPCNLSDE-UHFFFAOYSA-N 3,7-bis(dimethylamino)phenothiazin-5-ium Chemical compound C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 RBTBFTRPCNLSDE-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 239000005046 Chlorosilane Substances 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- XOJVVFBFDXDTEG-UHFFFAOYSA-N Norphytane Natural products CC(C)CCCC(C)CCCC(C)CCCC(C)C XOJVVFBFDXDTEG-UHFFFAOYSA-N 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 229910020175 SiOH Inorganic materials 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- 239000003570 air Substances 0.000 description 1
- 150000001343 alkyl silanes Chemical class 0.000 description 1
- 238000004164 analytical calibration Methods 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 238000005452 bending Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000004568 cement Substances 0.000 description 1
- 238000002144 chemical decomposition reaction Methods 0.000 description 1
- 238000005229 chemical vapour deposition Methods 0.000 description 1
- KOPOQZFJUQMUML-UHFFFAOYSA-N chlorosilane Chemical class Cl[SiH3] KOPOQZFJUQMUML-UHFFFAOYSA-N 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 125000003700 epoxy group Chemical group 0.000 description 1
- 239000003822 epoxy resin Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052743 krypton Inorganic materials 0.000 description 1
- DNNSSWSSYDEUBZ-UHFFFAOYSA-N krypton atom Chemical compound [Kr] DNNSSWSSYDEUBZ-UHFFFAOYSA-N 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 1
- 229960000907 methylthioninium chloride Drugs 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229910052754 neon Inorganic materials 0.000 description 1
- GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 description 1
- 229910052756 noble gas Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 238000001782 photodegradation Methods 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229910052704 radon Inorganic materials 0.000 description 1
- SYUHGPGVQRZVTB-UHFFFAOYSA-N radon atom Chemical compound [Rn] SYUHGPGVQRZVTB-UHFFFAOYSA-N 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000005060 rubber Substances 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 150000004756 silanes Chemical class 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229920001169 thermoplastic Polymers 0.000 description 1
- 239000004416 thermosoftening plastic Substances 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 229910052724 xenon Inorganic materials 0.000 description 1
- FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/52—Containers specially adapted for storing or dispensing a reagent
- B01L3/523—Containers specially adapted for storing or dispensing a reagent with means for closing or opening
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/52—Containers specially adapted for storing or dispensing a reagent
- B01L3/527—Containers specially adapted for storing or dispensing a reagent for a plurality of reagents
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
- B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0673—Handling of plugs of fluid surrounded by immiscible fluid
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0689—Sealing
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/04—Closures and closing means
- B01L2300/041—Connecting closures to device or container
- B01L2300/042—Caps; Plugs
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0832—Geometry, shape and general structure cylindrical, tube shaped
- B01L2300/0838—Capillaries
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
- B01L2300/087—Multiple sequential chambers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/06—Valves, specific forms thereof
- B01L2400/0677—Valves, specific forms thereof phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
- B01L2400/0683—Valves, specific forms thereof phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers mechanically breaking a wall or membrane within a channel or chamber
Definitions
- This application is directed to ampules for storing multiple liquid volumes and systems with a plurality of such ampules. More specifically, this application is directed to capillary ampules and capillary ampule systems with capillary ampules.
- ARMs are a class of materials used during chemical analysis as a qualitative and/or quantitative control for target compounds. As such, these ARM standards must be of particularly high purity and, when provided in solution, known concentration. ARM standards are prepared in advance to usage, where it is desirable for them to be stored for long periods of time. Commercially available ARM standards routinely have shelf lives greater than one year.
- the ARMs are contained in glass ampules that are hermetically sealed. Ampules have been used to contain, preserve, and deliver various materials dating back as far as 305 BCE.
- the modem ARM ampule is preferably glass which has been chemically treated to be chemically inert to the ARM components and prevent adsorption.
- the ampule glass is typically translucent or transparent and may be tinted to reduce photodegradation of the contents.
- ampules are filled with ARM mixtures at a known concentration. After filling the ampule, leaving an inert gas headspace, the seal is achieved by melting the glass ampule closed (“flame sealing”). To open, the ampule is sheared in order to access the analytic reference materials within, a portion of the liquid is then usually withdrawn with a pipette or syringe rather than being poured.
- the use of ampules may suffer from various drawbacks, including that ampules may be difficult to open, may result in and/or contaminate a sample with shattered glass, and may be time consuming to empty, among others.
- ARMS are complex combinations containing many different chemical components. Certain ARMs require multiple chemical compounds of known chemical incompatibility. Placing chemically incompatible compounds in the same ampule causes denaturing and degradation of those compounds. The denatured compounds change an analytic reference materials' chemical composition, leading to inaccurate chemical analysis.
- Opening multiple ampules is labor intensive, time consuming, and prone to end-user error during combination.
- User error along with chemical degradation, may lead to undesirable chemical analysis results or other errors in the data collected from various analytical techniques.
- Any container approach to improve the complexity and labor associated with ten separate ampules must maintain physical separation of the individual ARM liquid volumes to avoid undesired reactions.
- FIG. 1A-1C a standard ampule 100 is shown.
- FIG. 1A an exemplary unsealed standard ampule 101 is shown. Ampules
- ampule 100 known in the art may be amber colored glass in order to reduce light degradation of the compounds stored.
- Commercial ampules 100 may have borosilicate or other glass ampule walls 140 having a melting point sufficient to allow flame sealing the filling region 110 to create a hermetically sealed standard ampule 102.
- the contents of the standard ampule 100 are disposed in a container region 120 of the standard ampule 100 through the opening of the filling opening 150.
- Ampules typically have a shear point 130 (etched break line) for irreversibly opening the ampule.
- FIG. IB an exemplary sealed standard ampule 102 (storage condition) is shown.
- the previously open fdling region 110 of the unsealed standard ampule 101 of FIG. 1 A is transformed into a hermetically sealed region by forming a hermetic seal 160 from the fdling opening 150.
- Hermetic seal 160 is commonly achieved using heat, most commonly aflame to melt the glass fding opening 150 into an airtight seal.
- the sealed standard ampule 102 has a headspace region 171 which may include a gas over the liquid 170 level.
- the liquid 170 may include ARM dissolved in solvents such as, but not limited to, methanol, methylene chloride, hexane, water, acetonitrile.
- Headspace gas may be air or an inert gas such as nitrogen, helium, argon, other noble gas, or a combination thereof.
- Long term storage of analytical reference materials in glass required the inner surface of the ampule to be chemically inert. In cases where the glass is reactive with reference materials in solution, the glass surface may be chemically treated to create a physical barrier between the glass surface and the solution.
- deactivation chemistries are commonly employed including alkylsilane coating of the ampule inner surface. These procedures are known in the art.
- an opened standard ampule 103 (dispense condition) is formed by removing the hermetical seal 160 along the shear point 130 (etched break line) from the sealed standard ampule 102 of FIG. IB.
- some or all of the liquid contents 170 may be poured or pipetted into another container through the dispensing opening 180.
- a rough edge is typically left behind, exposed along the former shear point 130 (etched break line)by the removal of the hermetical seal 160.
- the liquid 170 may comprise a pure solvent or a solvent containing one or more ARM compound.
- the final concentration of the aliquot transferred from the ampule may be the same as the original liquid 170.
- Table 1 describes a commercially available ARM kit (Restek Corporation, catalog # 31971). 204 compounds are supplied in this kit. In this kit, ten ampules are provided to create the master standards mix. Ten ampules are required due to chemical reactivity of some compounds which, if all 204 compounds were provided in a single ampule, would reduce the product to an almost negligible shelf life.
- a capillary ampule includes a capillary tube having an outer diameter at an outer surface of the capillary tube, an inner diameter at an inner surface of the capillary tube, a wall thickness of a capillary wall between the outer diameter and the inner diameter, a first end, a second end, a length from the first end to the second end, and an internal volume formed by the inner diameter along the length, a first hermetic seal disposed at the first end of the capillary tube, a second hermetic seal disposed at the second end of the capillary tube, a first liquid volume disposed within the internal volume of the capillary tube, a first headspace volume disposed within the internal volume of the capillary tube between the first liquid volume and the first hermetic seal, and a second headspace volume disposed within the internal volume of the capillary tube between the first liquid volume and the second hermetic seal.
- a capillary ampule system includes a plurality of capillary ampules, wherein each capillary ampule of the plurality of capillary ampules includes a capillary tube having an outer diameter at an outer surface of the capillary tube, an inner diameter at an inner surface of the capillary tube, a wall thickness of a capillary wall between the outer diameter and the inner diameter, a first end, a second end, a length from the first end to the second end, and an internal volume formed by the inner diameter along the length, a first hermetic seal disposed at the first end of the capillary tube, a second hermetic seal disposed at the second end of the capillary tube, a first liquid volume disposed within the internal volume of the capillary tube, a first headspace volume disposed within the internal volume of the capillary tube between the first liquid volume and the first hermetic seal, and a second headspace volume disposed within the internal volume of the capillary tube between the
- a capillary ampule including a capillary tube having an outer diameter at an outer surface of the capillary tube, an inner diameter at an inner surface of the capillary tube, a wall thickness of a capillary wall between the outer diameter and the inner diameter, a first end, a second end, a length from the first end to the second end, and an internal volume formed by the inner diameter along the length, a first hermetic seal disposed at the first end of the capillary tube, a second hermetic seal disposed at the second end of the capillary tube, a first liquid volume disposed within the internal volume of the capillary tube, a first headspace volume disposed within the internal volume of the capillary tube between the first liquid volume and the first hermetic seal, and a second headspace volume disposed within the internal volume of the capillary tube between the first liquid volume and the second hermetic seal.
- the capillary ampule of any preceding clause further including a second liquid volume disposed within the internal volume of the capillary tube disposed between the first liquid volume and the second hermetic seal, the second headspace volume being disposed within the internal volume of the capillary tube between the second liquid volume and the second hermetic seal, and a barrier volume disposed within the internal volume between the first liquid volume and the second liquid volume, wherein the barrier volume maintains a separation of the first liquid volume and the second liquid volume such that the first liquid volume is isolated from the second liquid volume.
- the capillary ampule of any preceding clause wherein the first liquid volume includes a first analytical reference material and the second liquid volume includes a second analytical reference material, the first analytical reference material being compositionally distinct from the second analytical reference material.
- the capillary ampule of any preceding clause further including a third liquid volume disposed in the internal volume between the first liquid volume and the second liquid volume, the barrier volume including a first portion disposed between the first liquid volume and the third liquid volume and a second portion disposed between the third liquid volume and the second liquid volume, wherein the first portion of the barrier volume maintains a separation of the first liquid volume and the third liquid volume such that the first liquid volume is isolated from the third liquid volume and the second portion of the barrier volume maintains a separation of the second liquid volume and the third liquid volume such that the second liquid volume is isolated from the third liquid volume.
- the capillary ampule of any preceding clause further including a plurality of additional liquid volumes disposed in the internal volume between the first liquid volume and the second liquid volume, the barrier volume including a plurality of portions disposed between the first liquid volume, the second liquid volume and each of the plurality of additional liquid volumes, wherein the plurality of portions of the barrier volume maintains a separation of the first liquid volume, the second liquid volume and each of the plurality of additional liquid volumes such that the first liquid volume, the second liquid volume, and each of the plurality of additional liquid volumes are isolated from one another.
- capillary ampule of any preceding clause wherein the capillary tube is formed from a material selected from the group consisting of fused silica, borosilicate, polymer, metal, and combinations thereof.
- first hermetic seal is a first end cap and the second hermetic seal is a second end cap
- first end cap sealingly mates with at least one of the outer surface of the capillary tube or the inner surface of the capillary tube
- second end cap sealingly mates with at least one of the outer surface of the capillary tube or the inner surface of the capillary tube.
- first hermetic seal is a first end cap and the second hermetic seal is a second end cap, the first end cap sealingly mates with the outer surface of the capillary tube, and the second end cap sealingly mates with the inner surface of the capillary tube.
- first hermetic seal is a first end cap and the second hermetic seal is a second end cap, the first end cap sealingly mates with the inner surface of the capillary tube, and the second end cap sealingly mates with the outer surface of the capillary tube.
- the capillary ampule of any preceding clause wherein the capillary tube includes at least one rinse liquid volume disposed within the internal volume of the capillary tube.
- the capillary ampule of any preceding clause further including a housing, the capillary tube being at least partially disposed within an interior cavity of the housing.
- each of the first aperture of the housing and the second aperture of the housing is a luer lock.
- a capillary ampule system comprising a plurality of capillary ampules according to any preceding clause.
- a method for preparing an analytical reference material solution including opening the first hermetic seal and the second hermetic seal of a capillary ampule according to any preceding clause, dispensing all contents of the internal volume of the capillary tube into a container with a driving force, and mixing the contents of the internal volume of the capillary tube to form the analytical reference material solution.
- FIG. 1 A is a cross-sectional view of an unsealed ampule, according to the prior art.
- FIG. IB is a cross-sectional view of a sealed ampule, according to the prior art.
- FIG. 1C is a cross-sectional view of an opened ampule, according to the prior art.
- FIG. 2A is a cross-sectional view of a capillary ampule with a single liquid volume disposed therein.
- FIG. 2B is a cross-sectional view of a capillary ampule with two liquid volumes disposed therein, according to an embodiment of the present disclosure.
- FIG. 2C is a cross-sectional view of a capillary ampule with two liquid volumes disposed therein and external end caps, according to an embodiment of the present disclosure.
- FIG. 2D is a cross-sectional view of a capillary ampule with two liquid volumes disposed therein and internal end caps, according to an embodiment of the present disclosure.
- FIG. 3 is a schematic representation of the volume sequence in the capillary ampule of FIG. 2A, according to an embodiment of the present disclosure.
- FIG. 4 is a schematic representation of the volume sequence in the capillary ampule of FIGS. 2B-2D according to an embodiment of the present disclosure.
- FIG. 5 is a schematic representation of the volume sequence in a capillary ampule containing the individual volumes described in Table 1, according to an embodiment of the present disclosure.
- FIG. 6A is a cross-sectional view of a capillary ampule system with a plurality of capillary ampules having two liquid volumes disposed in each, according to an embodiment of the present disclosure.
- FIG. 6B is a cross-sectional view of a capillary ampule system with a plurality of capillary ampules having one, two, or three liquid volumes disposed in each, according to an embodiment of the present disclosure.
- FIG. 7A is a cross-sectional view of a capillary ampule system linear array, according to an embodiment of the present disclosure.
- FIG. 7B is a cross-sectional view of a capillary ampule system annular array, according to an embodiment of the present disclosure.
- FIG. 7C is a cross-sectional view of a capillary ampule system circular array, according to an embodiment of the present disclosure.
- FIG. 8A is a cross-sectional view of a capillary ampule disposed in a housing, according to an embodiment of the present disclosure.
- FIG. 8B is a cross-sectional view of another capillary ampule disposed in another housing, according to an embodiment of the present disclosure.
- FIG. 9A is a cross-sectional view of a capillary ampule disposed in a housing illustrating a process of breaking the capillary ampule, according to an embodiment of the present disclosure.
- FIG. 9B is a cross-sectional view of a capillary ampule disposed in a housing illustrating a process of dispensing the contents of the capillary ampule, according to an embodiment of the present disclosure.
- FIG. 10A is a cross-sectional view illustrating a system for filling a capillary ampule with ARM standards and other liquid volumes employing liquid containing syringes, gas containing syringes, and a 2-way switching valve in a first value position, according to an embodiment of the present disclosure.
- FIG. 10B is a cross-sectional view illustrating the system of FIG. 10A in a second valve filling position, according to an embodiment of the present disclosure.
- FIG. 11A is a cross-sectional view illustrating a system for filling a capillary ampule with ARM standards and other liquid volumes employing liquid containing syringes, gas containing syringes, and a 3 -way switching valve, according to an embodiment of the present disclosure.
- FIG. 1 IB is a cross-sectional view illustrating a system for filling a capillary ampule with ARM standards and other liquid volumes employing a liquid containing syringe, according to an embodiment of the present disclosure.
- the present ampules may promote the inclusion of the total number of ARM standard compounds in a single point of use technology while minimizing or eliminating chemical interactions between chemically labile compounds during storage, are scalable to accommodate any number of ARM standard compounds without increasing complexity for the end user, and promote for the aggregate ARM solution to be dispensable by a single motion from the end user.
- an ampule employs a hermetically sealed capillary tube as a container.
- the capillary tube is modified to store chemically labile compounds in the same container and, upon opening both ends of the capillary, dispense ARMs.
- analytical reference standards may be contained and preserved within hermetically sealed capillary tubes via flame sealed ends and upon breakage of said seals, may deliver operable reference material directly from the container.
- embodiments of the present invention may no longer require multiple separate ampules containing chemically labile compounds, but rather a singular entity to dispense reference material, saving space, reducing shipping costs, increasing accuracy, increasing precision, reducing time, or combinations thereof.
- hermetic seal means any type of sealing that makes a given object airtight (preventing the passage of air, oxygen, or other gases), including, but not limited to, airtight glass-to-glass (melted or fused) seals, glass-to-metal seals, and gas-impervious seals made with rubber, plastics, resins, and equivalent materials.
- capillary column indicates a tube having an inlet and an outlet and a channel therethrough.
- Capillary tubing may have any suitable inner diameter, including, but not limited to, an inner diameter of less than 3 mm, alternatively less than 2.5 mm, alternatively less than 2 mm, alternatively less than 1.5 mm, alternatively less than 1 mm, alternatively less than 0.5 mm.
- analytical reference materials are synonymous with one another and indicate solid, liquid, and gaseous compounds suspended in a solvent or gas at a known concentration with the intended use being for analytical calibration, quantitation, and verification purposes.
- fluid indicates liquids and gases. Such fluids may be pure compounds, mixtures of compounds, and (in the case of liquids) mixtures including dissolved solids.
- TD to deliver
- head space indicates a portion of the ampule reserved for an inert gas volume. The presence of the gas volume accommodates changes of the liquid volume due to thermal expansion.
- “storage state” indicates that the ampule is fdled with liquid and headspace gas, and all openings are hermetically sealed.
- dispenser state indicates the condition where the ampule has been opened to access the contents.
- Driving force indicates a force used to deliver the contents of a capillary ampule to a receiving container with the ampule open at both ends.
- Driving pressures may derive from gravity, or a positive pressure supplied by a pump, syringe, or other source.
- the driving force may be provided by a solid piston device or driven by either gas or liquid fluidic positive pressure.
- cohesive force indicates the intermolecular bonding of a substance in a liquid state where its mutual attractiveness promotes the liquid to maintain a certain shape.
- surface tension indicates the result of like molecules attracting together to form a bulk surface on the body of water.
- adheresive force indicates forces of attraction between liquid volumes and solid surfaces at their interfaces.
- deactivation indicates the chemical treatment or coating of the inner capillary wall to reduce wall-liquid interactions relating to adhesion, adsorption, or chemical reaction of the liquid volume contents to the capillary wall.
- Techniques for column deactivation using chlorosilanes are known to those skilled in the art.
- a capillary ampule 200 includes a capillary tube 202 having an outer diameter 204 at an outer surface 206 of the capillary tube 202, an inner diameter 208 at an inner surface 210 of the capillary tube 202, a wall thickness 214 of a capillary wall 212 between the outer diameter 204 and the inner diameter 208, a first end 216, a second end 218, a length 220 from the first end 216 to the second end 218, and an internal volume 222 formed by the inner diameter 208 along the length 220, a first hermetic seal 224 disposed at the first end 216 of the capillary tube 202, a second hermetic seal 226 disposed at the second end 218 of the capillary tube 202, a first liquid volume 228 disposed within the internal volume 222 of the capillary tube 202, a first headspace volume 230 disposed within the internal volume 222 of the capillary tube 202 between
- the first liquid volume may be any suitable material, including, but not limited to, an ARM.
- the capillary tube 202 may have any suitable geometry,
- the inner diameter 208 may be selected to maintain a stable liquid volume plug within the capillary. If the inner diameter 208 is too great, the liquid plug may change from the nominally cylindrical plug shape and then flow freely along the internal volume 222.
- Dominant properties relevant to maintaining a stable liquid plug include inner diameter 208 and the surface tension of the liquid volume. Factors relevant to a stable liquid volume plug include the cross-sectional area of the internal volume 222, the cohesive forces (surface tension) of the liquid, and the adhesive forces between the inner surface 210 and the liquid.
- Capillary tubing used for forming the capillary tube 202 may have any suitable inner diameter 208, including, but not limited to, for fused silica tubing, an inner diameter 208 of 0.10 mm to 3 mm, alternatively 0.15 mm to 2 mm, alternatively 0.25 mm to 1.5 mm, or combinations or subranges thereof.
- the length 220 of the capillary tube 202 may be selected based on the target volumes of individual liquid and gas volumes that are being stored within the internal volume 222, and the target final liquid volume after delivery.
- Capillary material is readily available in coils hundreds of meters in length, the final length based on the capillary diameter, and the target fluid volumes. Coiling the capillary tube 202 may promote a gross form factor that aids in handling and storage of the assembled capillary ampule 200.
- the capillary tube 202 is hermetically sealed and may contain the liquid contents of the capillary ampule 200 without exposure to the outside environment and without loss of any of the liquid contents.
- the first headspace volume 230 and the second headspace volume 232 may provide a “pressure cushion” to accommodate thermal expansion of the first liquid volume 228 and any additional liquid volumes disposed in the internal volume 222.
- the first headspace volume 230 and the second headspace volume 232 may also provide portions of the capillary tube 202 devoid of liquid which are suitable for breaking open the capillary tube 202 without trapping or loss of any liquid contents of the capillary tube 202.
- the first liquid volume 228 may include any suitable composition, including, but not limited to, an analytical reference material.
- the capillary ampule 200 further includes a second liquid volume 234 disposed within the internal volume 222 of the capillary tube 202 disposed between the first liquid volume 228 and the second hermetic seal 226, the second headspace volume 232 being disposed within the internal volume 222 of the capillary tube 202 between the second liquid volume 234 and the second hermetic seal 226.
- a barrier volume 236 disposed within the internal volume 222 between the first liquid volume 228 and the second liquid volume 234, the barrier volume 236 maintaining a separation of the first liquid volume 228 and the second liquid volume 234 such that the first liquid volume 228 is isolated from the second liquid volume 234.
- the barrier volume 236 may be any suitable material, including, but not limited to, a liquid, a solid, a gas, a gel, air, inert gases, nitrogen, helium, argon, neon, krypton, xenon, radon, or combinations thereof.
- the different liquid volumes may use the same solvent or a different solvent.
- the first liquid volume 228 and the second liquid volume 234 may be the same material or distinct materials.
- the material of the first liquid volume 228 and the material of the second liquid volume 234 are chemically incompatible with one another such that contacting the material of the first liquid volume 228 and the material of the second liquid volume 234 with one another would result in at least one of the material degrading or denaturing.
- first liquid volume 228 or the second liquid volume 234 may include an analytical reference material.
- first liquid volume 228 includes a first analytical reference material and the second liquid volume 234 includes a second analytical reference material, the first analytical reference material being compositionally distinct from the second analytical reference material.
- first analytical reference material is chemically incompatible with the second analytical reference material.
- the capillary ampule 200 may further include a third liquid volume 238 disposed in the internal volume 222 between the first liquid volume 228 and the second liquid volume 234, the barrier volume 236 including a first portion 240 disposed between the first liquid volume 228 and the third liquid volume 238 and a second portion 242 disposed between the third liquid volume 238 and the second liquid volume 234, wherein the first portion 240 of the barrier volume 236 maintains a separation of the first liquid volume 228 and the third liquid volume 238 such that the first liquid volume 228 is isolated from the third liquid volume 238 and the second portion 242 of the barrier volume 236 maintains a separation of the second liquid volume 234 and the third liquid volume 238 such that the second liquid volume 234 is isolated from the third liquid volume 238.
- the capillary ampule may further include any suitable number of additional liquid volumes disposed in the internal volume 222 between the first liquid volume 228 and the second liquid volume 234 separated by a corresponding number of additional portions of the barrier volume 236 (for example, FIG. 5) such that the first liquid volume 228, the second liquid volume 234, and each of the plurality of additional liquid volumes are isolated from one another, including, but not limited to, one additional liquid volume and one additional portion of the barrier volume 236, two additional liquid volumes and two additional portions of the barrier volume 236, three additional liquid volumes and three additional portions of the barrier volume 236, four additional liquid volumes and four additional portions of the barrier volume 236, five additional liquid volumes and five additional portions of the barrier volume 236, six additional liquid volumes and six additional portions of the barrier volume 236, seven additional liquid volumes and seven additional portions of the barrier volume 236, eight additional liquid volumes and eight additional portions of the barrier volume 236, nine additional liquid volumes and nine additional portions of the barrier volume 236, ten additional liquid volumes and ten additional portions of the barrier volume 236, seventeen additional liquid volumes and seventeen additional portions of the barrier volume
- the total number of portions of the barrier volume 236 is N-l with respect to the number (N) of liquid volumes.
- the first headspace volume 230, the second headspace volume 232, and the barrier volume 236 may be gaseous volumes, may be separatory liquid volumes immiscible with the adjacent liquid volumes, or combinations thereof.
- the barrier volume 236 may further be a solid, a liquid, a gel, combinations thereof, or combinations thereof with a gas.
- the capillary tube 202 may be formed from any suitable material, including, but not limited to, fused silica, borosilicate, polymer, metal, or combinations thereof.
- the capillary tube 202 may be opaque, translucent, or transparent. In one embodiment, the capillary tube 202 is colored to reduce light degradation of the compounds stored within. Materials with sufficiently low melting points may be flame sealed closed to form the first hermetic seal 224, the second hermetic seal 226, or both. In embodiments made from materials such as metal forming the first hermetic seal 224, the second hermetic seal 226, or both may be accomplished with a chemically bonded cap or plug, the plug material being impermeable to gases and moisture.
- the capillary tube 202 may include any suitable coating on the outer surface 206, including, but not limited to, a polyamide coating, and any suitable coating on the inner surface 210, including, but not limited to dimethyldi chlorosilane (“DMDCS”), which may adjust the hydrophobicity of the inner surface 210.
- DMDCS coating may provide surface deactivation in which the polar SiOH groups on the surface of bare silica tubing are replaced with nonpolar methyl groups. Coatings on the inner surface 210 may also render the inner surface 210 chemically inert.
- Coating the capillary tube 202 may employ any suitable technique, including, but not limited to, chemical vapor deposition (“C VD”) techniques or atomic layer deposition (“ALD”) techniques, which are known in the art such.
- C VD chemical vapor deposition
- ALD atomic layer deposition
- the outer surfaces 206 may be coated to increase the strength of the capillary tube 202, to tint the capillary tube 202, or both.
- the first hermetic seal 224 may be a first end cap 244 and the second hermetic seal 226 may be a second end cap 246.
- the first end cap 244 may sealingly mate with the outer surface 206 of the capillary tube 202, the inner surface 210 of the capillary tube 202, or both.
- the second end cap 246 may sealingly mate with the outer surface 206 of the capillary tube 202, the inner surface 210 of the capillary tube 202, or both.
- the first end cap 244 and the second end cap 246 may interface with the capillary tube 202 in the same manner or in a different manner.
- the first end cap 244 may have the same structure as the second end cap 246 or a different structure.
- the first end cap 244, the second end cap 246, or both may be formed from any suitable material, including, but not limited to, plastic or polymer materials, epoxies, glues, nonporous cements, cured polymers, thermoplastics heated above the melting point, or combinations thereof.
- low melting point (less than 300 °C) glass may be used.
- the low melting point glass premelt known as “frit,” is supplied as a powder or a paste.
- the glass frit may be introduced to the filling opening 150 either in its premelt or melted liquid states.
- the first hermetic seal 224, the second hermetic seal 226, or both may be achieved when the frit glass is subsequently cooled in place.
- An example of a low temperature melting point glass is VANEETECT® (Hitachi Chemical Co., Tokyo, Japan) with a working temperature range 220-300°C.
- VANEETECT® Hag Chemical Co., Tokyo, Japan
- Many low temperature glass compositions are formulated to bond tightly with glass and silica substrates, creating a hermetic seal.
- Suitable examples of lead free, low melting point, low reactivity glass frits are described in US Patent Nos. 10,913,680 and 10,252,938.
- a low vapor pressure epoxy resin may be employed for the first end cap 244, the second end cap 246 or both.
- a suitable resin is TORR SEAL® Low Vapor Pressure Epoxy (Kurt Lesker, Jefferson Hills, PA) which hardens at room temperature and creates a chemically resistant hermetic seal.
- the first end cap 244, the second end cap 246, or both, if disposed inside of the capillary tube 202, may be loaded into the inner volume 222 as a fluid and subsequently hardened, reacted, or cured in place.
- At least one of the first end cap 244 or the second end cap 246 may include a depression 248 configured to localize breakage of the capillary tube 202 (by twisting or bending).
- the capillary tube may include at least one rinse liquid volume disposed within the internal volume 222 of the capillary tube 202.
- the at least one rinse liquid volume having no ARM compounds, may be included to follow ARM volumes as they are dispensed from the capillary tube 202. While the capillary ampule 200 is sealed, rinse liquid volumes positioned between adjacent ARM volumes may act as a physical barrier to mitigate volume-to-volume chemical communication. In the dispense state, rinse solvent volumes following ARM volumes rinse residual ARM materials that may remain clinging to the inner surface 210. Rinse solvent volumes may also be employed to reach a desired final concentration upon evacuation of the capillary tube 202.
- the capillary ampule 200 further includes a housing 250, with the capillary tube 202 being at least partially disposed within an interior cavity 252 of the housing 250.
- the capillary ampule 200 may include one capillary tube 202 (FIG. 8A) or a plurality of capillary tubes 202 (FIG. 8B).
- the plurality of capillary tubes 202 may include a suitable number of capillary tubes, including, but not limited to, 2, alternatively 3, alternatively 4, alternatively 5, alternatively 6, alternatively more than 2, alternatively more than 3, alternatively more than 4, alternatively more than 5, alternatively more than 6.
- a portion of the capillary tube 202 including the first end 216 of the capillary tube 202 may extend out of the housing 250 through a first aperture 254 of the housing 250 and a portion of the capillary tube 202 including the second end 218 of the capillary tube 202 may extend out of the housing 250 through a second aperture 256 of the housing 250.
- Either or each of the first aperture 254 of the housing 250 or the second aperture 256 of the housing 250 may be any suitable connector, including, but not limited to, a luer lock.
- the first end 216 of the capillary tube 202 and the second end 218 of the capillary tube pass through the housing 250 may form an airtight seal with the housing 250.
- either or both of the first end 216 of the capillary tube 202 or the second end 218 of the capillary tube 202 may be mated with one or more adaptors of the housing 250 such that the one or more adaptors of the housing 250 are in fluid communication with either or both of the first aperture 254 or the second aperture 256 of the housing 250.
- Such adaptors of the housing 250 may include valves or frangible seals.
- the first end 216 of the capillary tube 202 and the second end 218 of the capillary tube pass through the housing 250 may form an airtight seal with the one or more adaptors of the housing 250.
- a portion of the capillary tube 202 including the first end 216 of the capillary tube 202 may extend out of the housing 250 through a first aperture 254 of the housing 250 and the second end 218 of the capillary tube 202 may be mated with an adaptor of the housing 250 such that the adaptor of the housing 250 is in fluid communication with the second aperture 256 of the housing 250, or the portion of the capillary tube 202 including the second end 218 of the capillary tube 202 may extend out of the housing 250 through a second aperture 256 of the housing 250 and the first end 216 of the capillary tube 202 may be mated with an adaptor of the housing 250 such that the adaptor of the housing 250 is in fluid communication with the first aperture 254 of the housing 250.
- a capillary ampule system 258 includes a plurality of capillary ampules 200.
- the capillary ampules 200 of the capillary ampule system 258 may be entirely independent of one another and sold or packaged as a kit, or the capillary ampule system 258 and capillary ampules 200 may be affixed to one another via any suitable connective scheme, including, but not limited to, being bound together, being adhered together, being integral with one another, or combinations thereof.
- the plurality of capillary ampules 200 may be affixed to one another in any suitable arrangement, including, but not limited to, a linear array (flat, side-by-side) (FIG. 7A), an annular array (FIG. 7B), a bundled array (FIG. 7B), or combinations thereof.
- a linear array flat, side-by-side
- annular array FIG. 7B
- a bundled array FIG. 7B
- the capillary ampule system 258 may include any suitable number capillary ampules 200, including, but not limited to, two capillary ampules 200, three capillary ampules 200, four capillary ampules 200, five capillary ampules 200, six capillary ampules 200, seven capillary ampules 200, eight capillary ampules 200, nine capillary ampules 200, ten capillary ampules 200, eleven capillary ampules 200, twelve capillary ampules 200, thirteen capillary ampules 200, fourteen capillary ampules 200, fifteen capillary ampules 200, sixteen capillary ampules 200, seventeen capillary ampules 200, eighteen capillary ampules 200, nineteen capillary ampules 200, twenty capillary ampules 200, twenty-one capillary ampules 200, twenty-two capillary ampules 200, twenty-
- Each of the capillary tubes 202 in the capillary ampule system 258 may be a different outer diameter 204, inner diameter 208, or length 220, be made from different materials, or have different inner surface 210 or outer surface 206 chemical treatments.
- a method for preparing an analytical reference material solution includes opening the first hermetic seal 224 and the second hermetic seal 226 of at least one capillary ampule 200 (the “dispense state”), dispensing all contents of the internal volume 222 of the at least one capillary tube 202 into a container with a driving force, and mixing the contents of the internal volume 222 of the at least one capillary tube 202 to form the analytical reference material solution.
- Opening the first hermetic seal 224 and the second hermetic seal 226 of at least one capillary ampule 200 may include using an abrasive cutting edge 282 run along the outer surface 206 of the capillary tube 202.
- headspace volumes e.g., the first headspace volume 230 and the second headspace volume 232
- the liquid contents e.g., the first liquid volume 228, the second liquid volume 234, and the third liquid volume 238, through the capillary tube 202.
- the final concentration of compounds from the capillary tube 202 is unchanged.
- the final concentration of compounds includes the aggregate volume of all liquids passing though the exit of the capillary tube 202.
- a syringe 260 or other source of positive pressure may be used to drive the liquid from the capillary tube 202.
- FIGS. 10A, 10B, 11A, and 1 IB methods for loading a capillary ampule 200 are shown.
- a loading apparatus 262 for filling capillary ampules 200 with ARM standards and other liquid volumes employing a liquidcontaining syringe 276, a gas-containing syringe 278, and a 2-way switching valve 264 is depicted.
- a syringe 260 filled with liquid 266 to be loaded into the capillary tube 202 and a syringe 260 filled with a gas are connected to the 2-way switching valve 264 toggled between positions “A” (FIG. 10A) and position “B” (FIG. 10B) along with an injection loop 268 having a known volume.
- the injection loop 268 is loaded with a precise volume of liquid 266 from syringe 260 in the “A” position or filled with the gas 270 from the other syringe 260 in the “B” position.
- the “A” position was employed to the fill injection loop 268 with liquid
- switching to the “B” position provides a route for the gas 270 to push the loop contents into the capillary.
- position “B” also permits the gas 270 to fill the capillary tube 202, either as first headspace volume 230, a second headspace volume 232, or a barrier volume 236.
- Switching valves having larger numbers of inputs and outputs and valve arrays linking more than one 2-way valve together are contemplated for capillary schemes loading more than one liquid volume.
- the capillary tube 202 In the unsealed state, the capillary tube 202 is open at the first end 216 and the second end 218.
- the capillary tube 202 is connected to the loading apparatus 262 through a connector 272.
- the capillary tube 202 is removed from the connector 272 and the first end 216 and the second end 218 are hermetically sealed.
- a loading apparatus 262 for filling capillary ampules 200 with ARM standards and other liquid volumes employing two liquid-containing syringes 276, a gas-containing syringe 278, and a 3-way switching valve 274 is depicted.
- valve position sequence 3-4-3-2-3 a volume of either liquid or gas is delivered during each valve position.
- the volume delivered to the capillary tube 202 is determined by the displacement from the liquid-containing syringe 276.
- a loading apparatus 262 for fdling capillary ampules 200 with ARM standards and other liquid volumes employs a syringe 260 prefdled with precise volumes of a first liquid volume 228, a second liquid volume 234, a first headspace volume 230, a second headspace volume 232, and a barrier volume 236.
- the entire contents of the syringe 620 are directly delivered to the capillary tube 202.
- FIGS. 3-5 depict filling schemes for capillary ampule 200.
- Figure 2(a) illustrates capillary ampule 200 filled with one liquid volume (Scheme 1) and Figures 2(b-d) two liquid volumes (Scheme 2).
- Table 2 discloses capillary lengths calculated for three capillary diameters describing Schemes 1-3.
- the capillary length is between 0.1 m and 10 m in length. Capillaries with geometries in these ranges are compatible with the liquid handling technologies described in FIG. 9B to dispense ARM liquids from a filled capillary, and FIGS. 10A, 10B, 11A, and 11B to fill capillaries with ARM liquids.
- Tris(pentafluorophenyl)borane (CAS #1109-15-5), >98% was purchased from TCI America and (tridecafluoro-l,l,2,2-tetrahydrooctyl)silane (CAS # 469904-32-3), 97%, was obtained from Gelest, Inc. (Morrisville, PA).
- Tris(perfluorophenyl)borane (123 pmol, 63 mg) was dispersed in 20 mL anhydrous dichloromethane in a 60 mL reagent bottle.
- (Tri decafluoro- 1,1, 2, 2-tetrahydrooctyl)silane (6.14 mmol, 1.61 mL) was then added to the bottle. Reagents were used immediately after preparation and then discarded.
- Rinsed capillaries were introduced to the reagent bottle through an airtight connection in the cap.
- the inlets of the capillaries in the bottle were immersed into the silane/catalyst solution.
- a nitrogen line was also introduced to the bottle through an airtight connection in the cap, and a head pressure was adjusted to 138 kPa for reagent flow through the capillaries.
- the silane solution was collected in an airtight bottle assembly and the nitrogen line was replaced with a vent line exhausting to a hood.
- Reagent was flowed through the capillaries, from one bottle to the other under a nitrogen blanket. When the volume of the first bottle was fully transferred to the second bottle, the gas line and vent lines were reversed and the reagent flowed in the opposite direction back to the first bottle.
- Deactivated capillaries (labeled “Fused Silica + CF3”) were then rinsed with 3 mL anhydrous dichloromethane per capillary. Capillaries were then dried under nitrogen flow at 60 °C for two hours. Capillary ends were then flame sealed for storage.
- DMDCS Dimethyldichlorosilane, CAS# 75-78-5) in toluene solution was prepared under a nitrogen blanket. DMDCS is highly reactive in water and care was taken to prevent reaction with atmospheric humidity.
- Reagent was flowed through the capillaries, from one bottle to the other under a nitrogen blanket. When the volume of the first bottle was fully transferred to the second bottle, the gas line and vent lines were reversed and the reagent flowed in the opposite direction back to the first bottle. Three full rinse cycles of the DMDCS solution was flowed through the capillary.
- Deactivated capillaries (labeled “Fused Silica + CF3”) were then rinsed with 3 mL anhydrous di chloromethane per capillary. Capillaries were then dried under nitrogen flow at 60 °C for two hours. Capillary ends were then flame sealed for storage.
- PTFE polytetrafluoroethylene tubing
- Scientific Commodities Inc. (0.25mm ID, cat# BB311-32).
- the degree of surface adsorption/absorption for a given solvent-capillary system is dependent on the solvent surface tension, solvent viscosity, capillary wall total surface area and smoothness, and the hydrophobic natures of the solvent and capillary wall.
- the capillary ampule exhibits little to no liquid retention. This promotes a quantitative transfer of the ARM fluid from the ampule, where the delivered fluid maintains the indicated sample composition and concentrations.
- the capillary deliver the same volume of liquid as was previously loaded. It is also preferable the component concentrations of the liquid are the same delivered as was loaded. For this it is beneficial that the capillary inner surface should be resistant to liquid volume retention, or selective retention of components within the liquid volume.
- both the Fused Silica + CF3 capillary and PTFE tubing exhibited very low surface retention of the liquid volume.
- the Fused Silica + CF3 capillary exhibited low liquid retention.
- the bare fused silica exhibited considerable retention, with the entire volume of liquid lost to the capillary walls before reaching the distal end of the column.
- a capillary loading system as illustrated in FIG. 10 was employed to fill five capillary lengths with the same volume. All capillaries 202 were fused silica, 0.32 mm ID, and previously treated with the CF3 coating.
- Nitrogen was employed as a capillary purge, and the gas volume “push” syringe 278 was charged with nitrogen 270.
- Two 250 pL gastight precision glass syringes were employed as the syringes 260.
- a fused silica capillary, approximately 120 cm in length and treated with CF3 was employed as the injection loop 268.
- Sample fused silica capillaries 202, approximately 200 cm in length and treated with CF3 were employed as the liquid volume receptacle.
- Methanol was employed as the first liquid volume 228.
- a syringe 278 filled with methanol 266 loaded the injection loop 750.
- Capillary 202 was first purged with nitrogen while the valve 264 was in the FIG. 10B configuration. Following the nitrogen purge, the valve 264 switched to the FIG. 10A configuration. A volume of methanol 266 was pushed from syringe 260 into the injection loop 268. This ensured a fixed, reproducible volume of methanol to the be transferred into capillary 202. Following the filling of injection loop 268, the valve 264 was switched back to the FIG. 10B configuration and the nitrogen 270 pushed the methanol volume from the loop 268 into capillary 202.
- a gravimetric approach to determining the precision of the capillary load involved measuring a fixed volume of liquid.
- the mass of capillary 202 was measured before and after loading, and the calculated mass difference is the methanol delivered.
- the coefficient of variation (%CV) was calculated using the Equation 1 :
- Capillary ampules 200 as described in FIG. 2A were constructed. 100 pL of standard solution was loaded into 2 m long bare fused silica capillaries, and silica + CF3 deactivated capillaries employing the loading fixture described in FIG. 10. Nitrogen gas was used as headspace volumes and the capillary ends were flame sealed. Three of both capillary types were immediately opened and the contents were analyzed by GC-FTD.
- bare silica capillary yielded concentration values greater than 99% of the compound concentration in DMSO solvent as measured for the ampule.
- the CF3 coated capillary yielded greater than 90% of the value.
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Abstract
A capillary ampule is disclosed including a capillary tube having an outer diameter at an outer surface, an inner diameter at an inner surface, a wall thickness of a capillary wall between the outer and inner diameters, first and second ends with a length therebetween, an internal volume formed by the inner diameter along the length, a first hermetic seal disposed at the first end, a second hermetic seal disposed at the second end, a first liquid volume disposed within the internal volume of the capillary tube, a first headspace volume disposed within the internal volume of the capillary tube between the first liquid volume and the first hermetic seal, and a second headspace volume disposed within the internal volume of the capillary tube between the first liquid volume and the second hermetic seal. A capillary ampule system is disclosed including a plurality of the capillary ampules.
Description
T
CAPILLARY AMPULES AND CAPILLARY AMPULE SYSTEMS
RELATED APPLICATIONS
[0001] This application claims the benefit of and priority to U.S. Provisional Patent Application No. 63/519,676, filed August 15, 2023, entitled “Capillary Ampules, Capillary Ampule Systems, and Methods For Preparing Anayltical Reference Material Solutions,” which is hereby incorporated by reference in its entirety.
FIELD OF THE INVENTION
[0002] This application is directed to ampules for storing multiple liquid volumes and systems with a plurality of such ampules. More specifically, this application is directed to capillary ampules and capillary ampule systems with capillary ampules.
BACKGROUND OF THE INVENTION
[0003] Analytic reference materials (“ARMs”) are a class of materials used during chemical analysis as a qualitative and/or quantitative control for target compounds. As such, these ARM standards must be of particularly high purity and, when provided in solution, known concentration. ARM standards are prepared in advance to usage, where it is desirable for them to be stored for long periods of time. Commercially available ARM standards routinely have shelf lives greater than one year.
[0004] Often, the ARMs are contained in glass ampules that are hermetically sealed. Ampules have been used to contain, preserve, and deliver various materials dating back as far as 305 BCE. The modem ARM ampule is preferably glass which has been chemically treated to be chemically inert to the ARM components and prevent adsorption. The ampule glass is typically translucent or transparent and may be tinted to reduce photodegradation of the contents.
[0005] During production, chemically deactivated ampules are filled with ARM mixtures at a known concentration. After filling the ampule, leaving an inert gas headspace, the seal is achieved by melting the glass ampule closed (“flame sealing”). To open, the ampule is sheared in order to access the analytic reference materials within, a portion of the liquid is then usually withdrawn
with a pipette or syringe rather than being poured. The use of ampules may suffer from various drawbacks, including that ampules may be difficult to open, may result in and/or contaminate a sample with shattered glass, and may be time consuming to empty, among others.
[0006] Most ARMS are complex combinations containing many different chemical components. Certain ARMs require multiple chemical compounds of known chemical incompatibility. Placing chemically incompatible compounds in the same ampule causes denaturing and degradation of those compounds. The denatured compounds change an analytic reference materials' chemical composition, leading to inaccurate chemical analysis.
[0007] It is therefore necessary to isolate chemically incompatible compounds to reach commercially viable shelf lives of these ARM standard solutions. As a result, chemically incompatible combinations are typically supplied in a kit having multiple ampules to keep the materials in pristine form until use. This problem is compounded by increasingly complex analytical methods that require an increasing number of components to make up the analytic reference material, resulting in so-called “mega” mixes that contain many individual ampoules in an analysis kit. Each ampoule contains a single analytic reference material or a combination of chemically compatible analytic reference materials. These kits require the end user to combine the contents of the ampoules, in correct amounts, to form the desired analytic reference materials. Opening multiple ampules is labor intensive, time consuming, and prone to end-user error during combination. User error, along with chemical degradation, may lead to undesirable chemical analysis results or other errors in the data collected from various analytical techniques. Any container approach to improve the complexity and labor associated with ten separate ampules must maintain physical separation of the individual ARM liquid volumes to avoid undesired reactions.
[0008] Referring to FIG. 1A-1C, a standard ampule 100 is shown.
[0009] Referring to FIG. 1A, an exemplary unsealed standard ampule 101 is shown. Ampules
100 known in the art may be amber colored glass in order to reduce light degradation of the compounds stored. Commercial ampules 100 may have borosilicate or other glass ampule walls 140 having a melting point sufficient to allow flame sealing the filling region 110 to create a hermetically sealed standard ampule 102. The contents of the standard ampule 100 are disposed in a container region 120 of the standard ampule 100 through the opening of the filling opening 150.
Ampules typically have a shear point 130 (etched break line) for irreversibly opening the ampule.
[0010] Referring to FIG. IB, an exemplary sealed standard ampule 102 (storage condition) is shown. The previously open fdling region 110 of the unsealed standard ampule 101 of FIG. 1 A is transformed into a hermetically sealed region by forming a hermetic seal 160 from the fdling opening 150. Hermetic seal 160 is commonly achieved using heat, most commonly aflame to melt the glass fding opening 150 into an airtight seal. The sealed standard ampule 102 has a headspace region 171 which may include a gas over the liquid 170 level. The liquid 170 may include ARM dissolved in solvents such as, but not limited to, methanol, methylene chloride, hexane, water, acetonitrile. Headspace gas may be air or an inert gas such as nitrogen, helium, argon, other noble gas, or a combination thereof. Long term storage of analytical reference materials in glass required the inner surface of the ampule to be chemically inert. In cases where the glass is reactive with reference materials in solution, the glass surface may be chemically treated to create a physical barrier between the glass surface and the solution. Several deactivation chemistries are commonly employed including alkylsilane coating of the ampule inner surface. These procedures are known in the art.
[0011] Referring to FIG. 1C, an opened standard ampule 103 (dispense condition) is formed by removing the hermetical seal 160 along the shear point 130 (etched break line) from the sealed standard ampule 102 of FIG. IB. In the dispense state, some or all of the liquid contents 170 may be poured or pipetted into another container through the dispensing opening 180. However, a rough edge is typically left behind, exposed along the former shear point 130 (etched break line)by the removal of the hermetical seal 160. The liquid 170 may comprise a pure solvent or a solvent containing one or more ARM compound. The final concentration of the aliquot transferred from the ampule may be the same as the original liquid 170.
[0012] Table 1 describes a commercially available ARM kit (Restek Corporation, catalog # 31971). 204 compounds are supplied in this kit. In this kit, ten ampules are provided to create the master standards mix. Ten ampules are required due to chemical reactivity of some compounds which, if all 204 compounds were provided in a single ampule, would reduce the product to an almost negligible shelf life.
[0013] To prepare the desired ARM solution, the user must open each of the ampules and
aliquot volumes from some or all of the ampules to create sample for chemical analysis. It is common in the art to then perform serial dilutions of the master mixtures to generate a quantitation calibration curve of the compounds.
[0014] Table 1 : Restek Corporation, catalog # 31971, LC Multiresidue Pesticide Kit, 10 ampules [compound names (CAS numbers)]
[0015] Accordingly, it would be desirable to have an improved design providing the total number of ARM standard compounds in a single point of use technology while minimizing or eliminating chemical interactions between chemically labile compounds during storage. It would further be desirable for the design to be scalable to accommodate any number of ARM standard compounds without increasing complexity for the end user and for the aggregate ARM solution to be dispensable by a single motion from the end user.
BRIEF DESCRIPTION OF THE INVENTION
[0016] In one exemplary embodiment, a capillary ampule includes a capillary tube having an outer diameter at an outer surface of the capillary tube, an inner diameter at an inner surface of the capillary tube, a wall thickness of a capillary wall between the outer diameter and the inner diameter, a first end, a second end, a length from the first end to the second end, and an internal volume formed by the inner diameter along the length, a first hermetic seal disposed at the first end of the capillary tube, a second hermetic seal disposed at the second end of the capillary tube, a first liquid volume disposed within the internal volume of the capillary tube, a first headspace volume disposed within the internal volume of the capillary tube between the first liquid volume and the first hermetic seal, and a second headspace volume disposed within the internal volume of the capillary tube between the first liquid volume and the second hermetic seal.
[0017] In another exemplary embodiment, a capillary ampule system includes a plurality of capillary ampules, wherein each capillary ampule of the plurality of capillary ampules includes a capillary tube having an outer diameter at an outer surface of the capillary tube, an inner diameter at an inner surface of the capillary tube, a wall thickness of a capillary wall between the outer diameter and the inner diameter, a first end, a second end, a length from the first end to the second end, and an internal volume formed by the inner diameter along the length, a first hermetic seal disposed at the first end of the capillary tube, a second hermetic seal disposed at the second end of the capillary tube, a first liquid volume disposed within the internal volume of the capillary tube, a first headspace volume disposed within the internal volume of the capillary tube between the first liquid volume and the first hermetic seal, and a second headspace volume disposed within the internal volume of the capillary tube between the first liquid volume and the second hermetic seal.
[0018] Further aspects of the subject matter of the present disclosure are provided by the
following clauses:
[0019] A capillary ampule including a capillary tube having an outer diameter at an outer surface of the capillary tube, an inner diameter at an inner surface of the capillary tube, a wall thickness of a capillary wall between the outer diameter and the inner diameter, a first end, a second end, a length from the first end to the second end, and an internal volume formed by the inner diameter along the length, a first hermetic seal disposed at the first end of the capillary tube, a second hermetic seal disposed at the second end of the capillary tube, a first liquid volume disposed within the internal volume of the capillary tube, a first headspace volume disposed within the internal volume of the capillary tube between the first liquid volume and the first hermetic seal, and a second headspace volume disposed within the internal volume of the capillary tube between the first liquid volume and the second hermetic seal.
[0020] The capillary ampule of the preceding clause, wherein the first liquid volume includes an analytical reference material.
[0021] The capillary ampule of any preceding clause, further including a second liquid volume disposed within the internal volume of the capillary tube disposed between the first liquid volume and the second hermetic seal, the second headspace volume being disposed within the internal volume of the capillary tube between the second liquid volume and the second hermetic seal, and a barrier volume disposed within the internal volume between the first liquid volume and the second liquid volume, wherein the barrier volume maintains a separation of the first liquid volume and the second liquid volume such that the first liquid volume is isolated from the second liquid volume.
[0022] The capillary ampule of any preceding clause, wherein at least one of the first liquid volume or the second liquid volume includes an analytical reference material.
[0023] The capillary ampule of any preceding clause, wherein the first liquid volume includes a first analytical reference material and the second liquid volume includes a second analytical reference material, the first analytical reference material being compositionally distinct from the second analytical reference material.
[0024] The capillary ampule of any preceding clause, wherein first analytical reference
material is chemically incompatible with the second analytical reference material.
[0025] The capillary ampule of any preceding clause, further including a third liquid volume disposed in the internal volume between the first liquid volume and the second liquid volume, the barrier volume including a first portion disposed between the first liquid volume and the third liquid volume and a second portion disposed between the third liquid volume and the second liquid volume, wherein the first portion of the barrier volume maintains a separation of the first liquid volume and the third liquid volume such that the first liquid volume is isolated from the third liquid volume and the second portion of the barrier volume maintains a separation of the second liquid volume and the third liquid volume such that the second liquid volume is isolated from the third liquid volume.
[0026] The capillary ampule of any preceding clause, further including a plurality of additional liquid volumes disposed in the internal volume between the first liquid volume and the second liquid volume, the barrier volume including a plurality of portions disposed between the first liquid volume, the second liquid volume and each of the plurality of additional liquid volumes, wherein the plurality of portions of the barrier volume maintains a separation of the first liquid volume, the second liquid volume and each of the plurality of additional liquid volumes such that the first liquid volume, the second liquid volume, and each of the plurality of additional liquid volumes are isolated from one another.
[0027] The capillary ampule of any preceding clause, wherein the first headspace volume, the second headspace volume, and the barrier volume are gaseous volumes.
[0028] The capillary ampule of any preceding clause, wherein the capillary tube is formed from a material selected from the group consisting of fused silica, borosilicate, polymer, metal, and combinations thereof.
[0029] The capillary ampule of any preceding clause, wherein the first hermetic seal is a first end cap and the second hermetic seal is a second end cap.
[0030] The capillary ampule of any preceding clause, wherein the first end cap sealingly mates with the outer surface of the capillary tube and the second end cap sealingly mates with the outer surface of the capillary tube.
[0031] The capillary ampule of any preceding clause, wherein the first end cap sealingly mates with the inner surface of the capillary tube and the second end cap sealingly mates with the inner surface of the capillary tube.
[0032] The capillary ampule of any preceding clause, wherein the first hermetic seal is a first end cap and the second hermetic seal is a second end cap, the first end cap sealingly mates with at least one of the outer surface of the capillary tube or the inner surface of the capillary tube, and the second end cap sealingly mates with at least one of the outer surface of the capillary tube or the inner surface of the capillary tube.
[0033] The capillary ampule of any preceding clause, wherein the first hermetic seal is a first end cap and the second hermetic seal is a second end cap, the first end cap sealingly mates with the outer surface of the capillary tube, and the second end cap sealingly mates with the inner surface of the capillary tube.
[0034] The capillary ampule of any preceding clause, wherein the first hermetic seal is a first end cap and the second hermetic seal is a second end cap, the first end cap sealingly mates with the inner surface of the capillary tube, and the second end cap sealingly mates with the outer surface of the capillary tube.
[0035] The capillary ampule of any preceding clause, wherein the first end cap sealingly mates with the outer surface of the capillary tube and the inner surface of the capillary tube and the second end cap sealingly mates with the outer surface of the capillary tube and the inner surface of the capillary tube.
[0036] The capillary ampule of any preceding clause, wherein at least one of the first end cap or the second end cap includes a depression configured to localize breakage of the capillary tube.
[0037] The capillary ampule of any preceding clause, wherein one of the first hermetic seal or the second hermetic seal is a first end cap and the other of the first hermetic seal or the second hermetic seal is flame-sealed.
[0038] The capillary ampule of any preceding clause, wherein the capillary tube includes at least one rinse liquid volume disposed within the internal volume of the capillary tube.
[0039] The capillary ampule of any preceding clause, further including a housing, the capillary tube being at least partially disposed within an interior cavity of the housing.
[0040] The capillary ampule of any preceding clause, wherein a portion of the capillary tube including the first end of the capillary tube extends out of the housing through a first aperture of the housing and a portion of the capillary tube including the second end of the capillary tube extends out of the housing through a second aperture of the housing.
[0041] The capillary ampule of any preceding clause, wherein each of the first aperture of the housing and the second aperture of the housing is a luer lock.
[0042] A capillary ampule system, comprising a plurality of capillary ampules according to any preceding clause.
[0043] The capillary ampule system of the preceding clause, wherein the plurality of capillary ampules are affixed to one another in a linear array.
[0044] The capillary ampule system of any preceding clause, wherein the plurality of capillary ampules are affixed to one another in an annular array.
[0045] A method for preparing an analytical reference material solution including opening the first hermetic seal and the second hermetic seal of a capillary ampule according to any preceding clause, dispensing all contents of the internal volume of the capillary tube into a container with a driving force, and mixing the contents of the internal volume of the capillary tube to form the analytical reference material solution.
BRIEF DESCRIPTION OF THE DRAWINGS
[0046] FIG. 1 A is a cross-sectional view of an unsealed ampule, according to the prior art.
[0047] FIG. IB is a cross-sectional view of a sealed ampule, according to the prior art.
[0048] FIG. 1C is a cross-sectional view of an opened ampule, according to the prior art.
[0049] FIG. 2A is a cross-sectional view of a capillary ampule with a single liquid volume disposed therein.
[0050] FIG. 2B is a cross-sectional view of a capillary ampule with two liquid volumes disposed therein, according to an embodiment of the present disclosure.
[0051] FIG. 2C is a cross-sectional view of a capillary ampule with two liquid volumes disposed therein and external end caps, according to an embodiment of the present disclosure.
[0052] FIG. 2D is a cross-sectional view of a capillary ampule with two liquid volumes disposed therein and internal end caps, according to an embodiment of the present disclosure.
[0053] FIG. 3 is a schematic representation of the volume sequence in the capillary ampule of FIG. 2A, according to an embodiment of the present disclosure.
[0054] FIG. 4 is a schematic representation of the volume sequence in the capillary ampule of FIGS. 2B-2D according to an embodiment of the present disclosure.
[0055] FIG. 5 is a schematic representation of the volume sequence in a capillary ampule containing the individual volumes described in Table 1, according to an embodiment of the present disclosure.
[0056] FIG. 6A is a cross-sectional view of a capillary ampule system with a plurality of capillary ampules having two liquid volumes disposed in each, according to an embodiment of the present disclosure.
[0057] FIG. 6B is a cross-sectional view of a capillary ampule system with a plurality of capillary ampules having one, two, or three liquid volumes disposed in each, according to an embodiment of the present disclosure.
[0058] FIG. 7A is a cross-sectional view of a capillary ampule system linear array, according to an embodiment of the present disclosure.
[0059] FIG. 7B is a cross-sectional view of a capillary ampule system annular array, according to an embodiment of the present disclosure.
[0060] FIG. 7C is a cross-sectional view of a capillary ampule system circular array, according to an embodiment of the present disclosure.
[0061] FIG. 8A is a cross-sectional view of a capillary ampule disposed in a housing, according to an embodiment of the present disclosure.
[0062] FIG. 8B is a cross-sectional view of another capillary ampule disposed in another housing, according to an embodiment of the present disclosure.
[0063] FIG. 9A is a cross-sectional view of a capillary ampule disposed in a housing illustrating a process of breaking the capillary ampule, according to an embodiment of the present disclosure.
[0064] FIG. 9B is a cross-sectional view of a capillary ampule disposed in a housing illustrating a process of dispensing the contents of the capillary ampule, according to an embodiment of the present disclosure.
[0065] FIG. 10A is a cross-sectional view illustrating a system for filling a capillary ampule with ARM standards and other liquid volumes employing liquid containing syringes, gas containing syringes, and a 2-way switching valve in a first value position, according to an embodiment of the present disclosure.
[0066] FIG. 10B is a cross-sectional view illustrating the system of FIG. 10A in a second valve filling position, according to an embodiment of the present disclosure.
[0067] FIG. 11A is a cross-sectional view illustrating a system for filling a capillary ampule with ARM standards and other liquid volumes employing liquid containing syringes, gas containing syringes, and a 3 -way switching valve, according to an embodiment of the present disclosure.
[0068] FIG. 1 IB is a cross-sectional view illustrating a system for filling a capillary ampule with ARM standards and other liquid volumes employing a liquid containing syringe, according to an embodiment of the present disclosure.
[0069] Wherever possible, the same reference numbers will be used throughout the drawings to represent the same parts.
DETAILED DESCRIPTION OF THE INVENTION
[0070] The present ampules, in comparison to ampules lacking one or more of the features described herein, may promote the inclusion of the total number of ARM standard compounds in a single point of use technology while minimizing or eliminating chemical interactions between chemically labile compounds during storage, are scalable to accommodate any number of ARM standard compounds without increasing complexity for the end user, and promote for the aggregate ARM solution to be dispensable by a single motion from the end user.
[0071] In one embodiment, an ampule employs a hermetically sealed capillary tube as a container. The capillary tube is modified to store chemically labile compounds in the same container and, upon opening both ends of the capillary, dispense ARMs. In a further embodiment, analytical reference standards may be contained and preserved within hermetically sealed capillary tubes via flame sealed ends and upon breakage of said seals, may deliver operable reference material directly from the container. In comparison with ampules lacking one or more of the features disclosed herein, embodiments of the present invention may no longer require multiple separate ampules containing chemically labile compounds, but rather a singular entity to dispense reference material, saving space, reducing shipping costs, increasing accuracy, increasing precision, reducing time, or combinations thereof.
[0072] As used herein, “about” indicates a variance of up to 10% of the value so modified, and specifically includes the absolute value as well, such that “about 2” discloses both a range from 1.8 to 2.2 as well as 2.
[0073] As used herein, “ampul,” “ampule,” and “ampoule,” are synonymous with each other.
[0074] As used herein, “hermetic seal” means any type of sealing that makes a given object airtight (preventing the passage of air, oxygen, or other gases), including, but not limited to, airtight glass-to-glass (melted or fused) seals, glass-to-metal seals, and gas-impervious seals made with rubber, plastics, resins, and equivalent materials.
[0075] As used herein, “capillary column’” indicates a tube having an inlet and an outlet and a channel therethrough. Capillary tubing may have any suitable inner diameter, including, but not limited to, an inner diameter of less than 3 mm, alternatively less than 2.5 mm, alternatively less than 2 mm, alternatively less than 1.5 mm, alternatively less than 1 mm, alternatively less than 0.5
mm.
[0076] As used herein, “analytical reference materials,” “standards,” and “ARM” are synonymous with one another and indicate solid, liquid, and gaseous compounds suspended in a solvent or gas at a known concentration with the intended use being for analytical calibration, quantitation, and verification purposes.
[0077] As used herein, “fluid” indicates liquids and gases. Such fluids may be pure compounds, mixtures of compounds, and (in the case of liquids) mixtures including dissolved solids.
[0078] As used herein, “to deliver” (“TD”) indicates that the delivered quantity of liquid corresponds to the liquid volumes loaded into the ampule. The liquid transfer is quantitative, and completely empties the ampule of liquid.
[0079] As used herein, “head space” indicates a portion of the ampule reserved for an inert gas volume. The presence of the gas volume accommodates changes of the liquid volume due to thermal expansion.
[0080] As used herein, “storage state” indicates that the ampule is fdled with liquid and headspace gas, and all openings are hermetically sealed.
[0081] As used herein, “dispense state” indicates the condition where the ampule has been opened to access the contents.
[0082] As used herein, “driving force” indicates a force used to deliver the contents of a capillary ampule to a receiving container with the ampule open at both ends. Driving pressures may derive from gravity, or a positive pressure supplied by a pump, syringe, or other source. The driving force may be provided by a solid piston device or driven by either gas or liquid fluidic positive pressure.
[0083] As used herein, “cohesive force” indicates the intermolecular bonding of a substance in a liquid state where its mutual attractiveness promotes the liquid to maintain a certain shape.
[0084] As used herein, “surface tension” indicates the result of like molecules attracting together
to form a bulk surface on the body of water.
[0085] As used herein, “adhesive force” indicates forces of attraction between liquid volumes and solid surfaces at their interfaces.
[0086] As used herein, “deactivation” indicates the chemical treatment or coating of the inner capillary wall to reduce wall-liquid interactions relating to adhesion, adsorption, or chemical reaction of the liquid volume contents to the capillary wall. Techniques for column deactivation using chlorosilanes are known to those skilled in the art.
[0087] Referring to FIGS. 2A and 3, in one embodiment, a capillary ampule 200 includes a capillary tube 202 having an outer diameter 204 at an outer surface 206 of the capillary tube 202, an inner diameter 208 at an inner surface 210 of the capillary tube 202, a wall thickness 214 of a capillary wall 212 between the outer diameter 204 and the inner diameter 208, a first end 216, a second end 218, a length 220 from the first end 216 to the second end 218, and an internal volume 222 formed by the inner diameter 208 along the length 220, a first hermetic seal 224 disposed at the first end 216 of the capillary tube 202, a second hermetic seal 226 disposed at the second end 218 of the capillary tube 202, a first liquid volume 228 disposed within the internal volume 222 of the capillary tube 202, a first headspace volume 230 disposed within the internal volume 222 of the capillary tube 202 between the first liquid volume 228 and the first hermetic seal 224, and a second headspace volume 232 disposed within the internal volume 222 of the capillary tube 202 between the first liquid volume 228 and the second hermetic seal 226.
[0088] The first liquid volume may be any suitable material, including, but not limited to, an ARM.
[0089] The capillary tube 202 may have any suitable geometry, The inner diameter 208 may be selected to maintain a stable liquid volume plug within the capillary. If the inner diameter 208 is too great, the liquid plug may change from the nominally cylindrical plug shape and then flow freely along the internal volume 222. Dominant properties relevant to maintaining a stable liquid plug include inner diameter 208 and the surface tension of the liquid volume. Factors relevant to a stable liquid volume plug include the cross-sectional area of the internal volume 222, the cohesive forces (surface tension) of the liquid, and the adhesive forces between the inner surface 210 and the liquid.
[0090] Capillary tubing used for forming the capillary tube 202 may have any suitable inner diameter 208, including, but not limited to, for fused silica tubing, an inner diameter 208 of 0.10 mm to 3 mm, alternatively 0.15 mm to 2 mm, alternatively 0.25 mm to 1.5 mm, or combinations or subranges thereof. The length 220 of the capillary tube 202 may be selected based on the target volumes of individual liquid and gas volumes that are being stored within the internal volume 222, and the target final liquid volume after delivery. Capillary material is readily available in coils hundreds of meters in length, the final length based on the capillary diameter, and the target fluid volumes. Coiling the capillary tube 202 may promote a gross form factor that aids in handling and storage of the assembled capillary ampule 200.
[0091] By virtue of the first hermetic seal 224 and the second hermetic seal 226, the capillary tube 202 is hermetically sealed and may contain the liquid contents of the capillary ampule 200 without exposure to the outside environment and without loss of any of the liquid contents.
[0092] The first headspace volume 230 and the second headspace volume 232 may provide a “pressure cushion” to accommodate thermal expansion of the first liquid volume 228 and any additional liquid volumes disposed in the internal volume 222. The first headspace volume 230 and the second headspace volume 232 may also provide portions of the capillary tube 202 devoid of liquid which are suitable for breaking open the capillary tube 202 without trapping or loss of any liquid contents of the capillary tube 202.
[0093] The first liquid volume 228 may include any suitable composition, including, but not limited to, an analytical reference material.
[0094] Referring to FIGS. 2B-2D and 4, in a further embodiment, the capillary ampule 200 further includes a second liquid volume 234 disposed within the internal volume 222 of the capillary tube 202 disposed between the first liquid volume 228 and the second hermetic seal 226, the second headspace volume 232 being disposed within the internal volume 222 of the capillary tube 202 between the second liquid volume 234 and the second hermetic seal 226. A barrier volume 236 disposed within the internal volume 222 between the first liquid volume 228 and the second liquid volume 234, the barrier volume 236 maintaining a separation of the first liquid volume 228 and the second liquid volume 234 such that the first liquid volume 228 is isolated from the second liquid volume 234.
[0095] The barrier volume 236 may be any suitable material, including, but not limited to, a liquid, a solid, a gas, a gel, air, inert gases, nitrogen, helium, argon, neon, krypton, xenon, radon, or combinations thereof. The different liquid volumes may use the same solvent or a different solvent.
[0096] The first liquid volume 228 and the second liquid volume 234 may be the same material or distinct materials. In one embodiment, the material of the first liquid volume 228 and the material of the second liquid volume 234 are chemically incompatible with one another such that contacting the material of the first liquid volume 228 and the material of the second liquid volume 234 with one another would result in at least one of the material degrading or denaturing.
[0097] One or both of the first liquid volume 228 or the second liquid volume 234 may include an analytical reference material. In one embodiment, the first liquid volume 228 includes a first analytical reference material and the second liquid volume 234 includes a second analytical reference material, the first analytical reference material being compositionally distinct from the second analytical reference material. In a further embodiment, the first analytical reference material is chemically incompatible with the second analytical reference material.
[0098] Referring to FIG. 6B, the capillary ampule 200 may further include a third liquid volume 238 disposed in the internal volume 222 between the first liquid volume 228 and the second liquid volume 234, the barrier volume 236 including a first portion 240 disposed between the first liquid volume 228 and the third liquid volume 238 and a second portion 242 disposed between the third liquid volume 238 and the second liquid volume 234, wherein the first portion 240 of the barrier volume 236 maintains a separation of the first liquid volume 228 and the third liquid volume 238 such that the first liquid volume 228 is isolated from the third liquid volume 238 and the second portion 242 of the barrier volume 236 maintains a separation of the second liquid volume 234 and the third liquid volume 238 such that the second liquid volume 234 is isolated from the third liquid volume 238. The capillary ampule may further include any suitable number of additional liquid volumes disposed in the internal volume 222 between the first liquid volume 228 and the second liquid volume 234 separated by a corresponding number of additional portions of the barrier volume 236 (for example, FIG. 5) such that the first liquid volume 228, the second liquid volume 234, and each of the plurality of additional liquid volumes are isolated from one another, including, but not limited to, one additional liquid volume and one additional portion of the barrier volume
236, two additional liquid volumes and two additional portions of the barrier volume 236, three additional liquid volumes and three additional portions of the barrier volume 236, four additional liquid volumes and four additional portions of the barrier volume 236, five additional liquid volumes and five additional portions of the barrier volume 236, six additional liquid volumes and six additional portions of the barrier volume 236, seven additional liquid volumes and seven additional portions of the barrier volume 236, eight additional liquid volumes and eight additional portions of the barrier volume 236, nine additional liquid volumes and nine additional portions of the barrier volume 236, ten additional liquid volumes and ten additional portions of the barrier volume 236, seventeen additional liquid volumes and seventeen additional portions of the barrier volume 236 (FIG. 5), more than ten additional liquid volumes and more than ten additional portions of the barrier volume 236, more than fifty additional liquid volumes and more than fifty additional portions of the barrier volume 236, or more than one-hundred additional liquid volumes and more than one-hundred additional portions of the barrier volume 236. In one embodiment, the total number of portions of the barrier volume 236 is N-l with respect to the number (N) of liquid volumes.
[0099] Referring to FIGS. 2A-2D, 6A, and 6B, the first headspace volume 230, the second headspace volume 232, and the barrier volume 236 may be gaseous volumes, may be separatory liquid volumes immiscible with the adjacent liquid volumes, or combinations thereof. The barrier volume 236 may further be a solid, a liquid, a gel, combinations thereof, or combinations thereof with a gas.
[0100] The capillary tube 202 may be formed from any suitable material, including, but not limited to, fused silica, borosilicate, polymer, metal, or combinations thereof. The capillary tube 202 may be opaque, translucent, or transparent. In one embodiment, the capillary tube 202 is colored to reduce light degradation of the compounds stored within. Materials with sufficiently low melting points may be flame sealed closed to form the first hermetic seal 224, the second hermetic seal 226, or both. In embodiments made from materials such as metal forming the first hermetic seal 224, the second hermetic seal 226, or both may be accomplished with a chemically bonded cap or plug, the plug material being impermeable to gases and moisture.
[0101] The capillary tube 202 may include any suitable coating on the outer surface 206,
including, but not limited to, a polyamide coating, and any suitable coating on the inner surface 210, including, but not limited to dimethyldi chlorosilane (“DMDCS”), which may adjust the hydrophobicity of the inner surface 210. The DMDCS coating may provide surface deactivation in which the polar SiOH groups on the surface of bare silica tubing are replaced with nonpolar methyl groups. Coatings on the inner surface 210 may also render the inner surface 210 chemically inert. Coating the capillary tube 202 may employ any suitable technique, including, but not limited to, chemical vapor deposition (“C VD”) techniques or atomic layer deposition (“ALD”) techniques, which are known in the art such. The outer surfaces 206 may be coated to increase the strength of the capillary tube 202, to tint the capillary tube 202, or both.
[0102] Referring to FIGS. 2C and 2D, the first hermetic seal 224 may be a first end cap 244 and the second hermetic seal 226 may be a second end cap 246. The first end cap 244 may sealingly mate with the outer surface 206 of the capillary tube 202, the inner surface 210 of the capillary tube 202, or both. The second end cap 246 may sealingly mate with the outer surface 206 of the capillary tube 202, the inner surface 210 of the capillary tube 202, or both. The first end cap 244 and the second end cap 246 may interface with the capillary tube 202 in the same manner or in a different manner. The first end cap 244 may have the same structure as the second end cap 246 or a different structure. The first end cap 244, the second end cap 246, or both may be formed from any suitable material, including, but not limited to, plastic or polymer materials, epoxies, glues, nonporous cements, cured polymers, thermoplastics heated above the melting point, or combinations thereof. For ease of manufacturing the first end cap 244, the second end cap 246, or both, low melting point (less than 300 °C) glass may be used. The low melting point glass premelt, known as “frit,” is supplied as a powder or a paste. The glass frit may be introduced to the filling opening 150 either in its premelt or melted liquid states. The first hermetic seal 224, the second hermetic seal 226, or both may be achieved when the frit glass is subsequently cooled in place. An example of a low temperature melting point glass is VANEETECT® (Hitachi Chemical Co., Tokyo, Japan) with a working temperature range 220-300°C. Many low temperature glass compositions are formulated to bond tightly with glass and silica substrates, creating a hermetic seal. Suitable examples of lead free, low melting point, low reactivity glass frits are described in US Patent Nos. 10,913,680 and 10,252,938. Alternatively, a low vapor pressure epoxy resin may be employed for the first end cap 244, the second end cap 246 or both. An example of a suitable resin is TORR SEAL® Low Vapor Pressure Epoxy (Kurt Lesker, Jefferson Hills, PA) which
hardens at room temperature and creates a chemically resistant hermetic seal. The first end cap 244, the second end cap 246, or both, if disposed inside of the capillary tube 202, may be loaded into the inner volume 222 as a fluid and subsequently hardened, reacted, or cured in place.
[0103] At least one of the first end cap 244 or the second end cap 246 may include a depression 248 configured to localize breakage of the capillary tube 202 (by twisting or bending).
[0104] Referring to FIGS. 2A-D, 6A and 6B, the capillary tube may include at least one rinse liquid volume disposed within the internal volume 222 of the capillary tube 202. The at least one rinse liquid volume, having no ARM compounds, may be included to follow ARM volumes as they are dispensed from the capillary tube 202. While the capillary ampule 200 is sealed, rinse liquid volumes positioned between adjacent ARM volumes may act as a physical barrier to mitigate volume-to-volume chemical communication. In the dispense state, rinse solvent volumes following ARM volumes rinse residual ARM materials that may remain clinging to the inner surface 210. Rinse solvent volumes may also be employed to reach a desired final concentration upon evacuation of the capillary tube 202.
[0105] Referring to FIGS. 8A, 8B, 9A, and 9B, in one embodiment, the capillary ampule 200 further includes a housing 250, with the capillary tube 202 being at least partially disposed within an interior cavity 252 of the housing 250. The capillary ampule 200 may include one capillary tube 202 (FIG. 8A) or a plurality of capillary tubes 202 (FIG. 8B). The plurality of capillary tubes 202 may include a suitable number of capillary tubes, including, but not limited to, 2, alternatively 3, alternatively 4, alternatively 5, alternatively 6, alternatively more than 2, alternatively more than 3, alternatively more than 4, alternatively more than 5, alternatively more than 6.
[0106] In a further embodiment, a portion of the capillary tube 202 including the first end 216 of the capillary tube 202 may extend out of the housing 250 through a first aperture 254 of the housing 250 and a portion of the capillary tube 202 including the second end 218 of the capillary tube 202 may extend out of the housing 250 through a second aperture 256 of the housing 250. Either or each of the first aperture 254 of the housing 250 or the second aperture 256 of the housing 250 may be any suitable connector, including, but not limited to, a luer lock. The first end 216 of the capillary tube 202 and the second end 218 of the capillary tube pass through the housing 250 may form an airtight seal with the housing 250.
[0107] In an alternate further embodiment, either or both of the first end 216 of the capillary tube 202 or the second end 218 of the capillary tube 202 may be mated with one or more adaptors of the housing 250 such that the one or more adaptors of the housing 250 are in fluid communication with either or both of the first aperture 254 or the second aperture 256 of the housing 250. Such adaptors of the housing 250 may include valves or frangible seals. The first end 216 of the capillary tube 202 and the second end 218 of the capillary tube pass through the housing 250 may form an airtight seal with the one or more adaptors of the housing 250.
[0108] In a further alternative embodiment, a portion of the capillary tube 202 including the first end 216 of the capillary tube 202 may extend out of the housing 250 through a first aperture 254 of the housing 250 and the second end 218 of the capillary tube 202 may be mated with an adaptor of the housing 250 such that the adaptor of the housing 250 is in fluid communication with the second aperture 256 of the housing 250, or the portion of the capillary tube 202 including the second end 218 of the capillary tube 202 may extend out of the housing 250 through a second aperture 256 of the housing 250 and the first end 216 of the capillary tube 202 may be mated with an adaptor of the housing 250 such that the adaptor of the housing 250 is in fluid communication with the first aperture 254 of the housing 250.
[0109] Referring to FIGS. 6A, 6B, and 7A-7C, in one embodiment, a capillary ampule system 258 includes a plurality of capillary ampules 200. The capillary ampules 200 of the capillary ampule system 258 may be entirely independent of one another and sold or packaged as a kit, or the capillary ampule system 258 and capillary ampules 200 may be affixed to one another via any suitable connective scheme, including, but not limited to, being bound together, being adhered together, being integral with one another, or combinations thereof. The plurality of capillary ampules 200, if affixed to one another, may be affixed to one another in any suitable arrangement, including, but not limited to, a linear array (flat, side-by-side) (FIG. 7A), an annular array (FIG. 7B), a bundled array (FIG. 7B), or combinations thereof.
[0110] The capillary ampule system 258 may include any suitable number capillary ampules 200, including, but not limited to, two capillary ampules 200, three capillary ampules 200, four capillary ampules 200, five capillary ampules 200, six capillary ampules 200, seven capillary ampules 200, eight capillary ampules 200, nine capillary ampules 200, ten capillary ampules 200, eleven
capillary ampules 200, twelve capillary ampules 200, thirteen capillary ampules 200, fourteen capillary ampules 200, fifteen capillary ampules 200, sixteen capillary ampules 200, seventeen capillary ampules 200, eighteen capillary ampules 200, nineteen capillary ampules 200, twenty capillary ampules 200, twenty-one capillary ampules 200, twenty-two capillary ampules 200, twenty-three capillary ampules 200, twenty-four capillary ampules 200, more than two capillary ampules 200, more than three capillary ampules 200, more than four capillary ampules 200, more than five capillary ampules 200, more than six capillary ampules 200, more than seven capillary ampules 200, more than eight capillary ampules 200, more than nine capillary ampules 200, more than ten capillary ampules 200, more than eleven capillary ampules 200, more than twelve capillary ampules 200, more than thirteen capillary ampules 200, more than fourteen capillary ampules 200, more than fifteen capillary ampules 200, more than sixteen capillary ampules 200, more than seventeen capillary ampules 200, more than eighteen capillary ampules 200, more than nineteen capillary ampules 200, more than twenty capillary ampules 200, more than twenty-one capillary ampules 200, more than twenty-two capillary ampules 200, more than twenty-three capillary ampules 200, or more than twenty-four capillary ampules 200.
[0111] Each of the capillary tubes 202 in the capillary ampule system 258 may be a different outer diameter 204, inner diameter 208, or length 220, be made from different materials, or have different inner surface 210 or outer surface 206 chemical treatments.
[0112] Referring to FIGS. 9A and 9B, in one embodiment, a method for preparing an analytical reference material solution includes opening the first hermetic seal 224 and the second hermetic seal 226 of at least one capillary ampule 200 (the “dispense state”), dispensing all contents of the internal volume 222 of the at least one capillary tube 202 into a container with a driving force, and mixing the contents of the internal volume 222 of the at least one capillary tube 202 to form the analytical reference material solution. Opening the first hermetic seal 224 and the second hermetic seal 226 of at least one capillary ampule 200 may include using an abrasive cutting edge 282 run along the outer surface 206 of the capillary tube 202.
[0113] In the dispense state, headspace volumes (e.g., the first headspace volume 230 and the second headspace volume 232) may function as pistons to move the liquid contents (e.g., the first liquid volume 228, the second liquid volume 234, and the third liquid volume 238) through the
capillary tube 202. Tn the case where gas is employed to expel the liquid contents of the capillary tube 202, the final concentration of compounds from the capillary tube 202 is unchanged. In cases where another liquid is employed as a dispense head pressure, the final concentration of compounds includes the aggregate volume of all liquids passing though the exit of the capillary tube 202. For either gas or liquid, a syringe 260 or other source of positive pressure may be used to drive the liquid from the capillary tube 202.
[0114] Referring to FIGS. 10A, 10B, 11A, and 1 IB, methods for loading a capillary ampule 200 are shown.
[0115] Referring to FIGS. 10A and 10B, in one embodiment, a loading apparatus 262 for filling capillary ampules 200 with ARM standards and other liquid volumes employing a liquidcontaining syringe 276, a gas-containing syringe 278, and a 2-way switching valve 264 is depicted. A syringe 260 filled with liquid 266 to be loaded into the capillary tube 202 and a syringe 260 filled with a gas are connected to the 2-way switching valve 264 toggled between positions “A” (FIG. 10A) and position “B” (FIG. 10B) along with an injection loop 268 having a known volume. The injection loop 268 is loaded with a precise volume of liquid 266 from syringe 260 in the “A” position or filled with the gas 270 from the other syringe 260 in the “B” position. In the case where first the “A” position was employed to the fill injection loop 268 with liquid, switching to the “B” position provides a route for the gas 270 to push the loop contents into the capillary. When the injection loop 268 is empty of liquid, position “B” also permits the gas 270 to fill the capillary tube 202, either as first headspace volume 230, a second headspace volume 232, or a barrier volume 236. Switching valves having larger numbers of inputs and outputs and valve arrays linking more than one 2-way valve together are contemplated for capillary schemes loading more than one liquid volume. In the unsealed state, the capillary tube 202 is open at the first end 216 and the second end 218. The capillary tube 202 is connected to the loading apparatus 262 through a connector 272. Following filling, the capillary tube 202 is removed from the connector 272 and the first end 216 and the second end 218 are hermetically sealed.
[0116] Referring to FIG. 11A, in another embodiment a loading apparatus 262 for filling capillary ampules 200 with ARM standards and other liquid volumes employing two liquid-containing syringes 276, a gas-containing syringe 278, and a 3-way switching valve 274 is depicted. With the
valve position sequence 3-4-3-2-3, a volume of either liquid or gas is delivered during each valve position. In this embodiment, the volume delivered to the capillary tube 202 is determined by the displacement from the liquid-containing syringe 276.
[0117] Referring to FIG. 11(b), in another embodiment, a loading apparatus 262 for fdling capillary ampules 200 with ARM standards and other liquid volumes employs a syringe 260 prefdled with precise volumes of a first liquid volume 228, a second liquid volume 234, a first headspace volume 230, a second headspace volume 232, and a barrier volume 236. In this setup the entire contents of the syringe 620 are directly delivered to the capillary tube 202.
EXAMPLES
[0118] Examples of filled capillary ampules.
[0119] FIGS. 3-5 depict filling schemes for capillary ampule 200. Figure 2(a) illustrates capillary ampule 200 filled with one liquid volume (Scheme 1) and Figures 2(b-d) two liquid volumes (Scheme 2).
[0120] Table 2 discloses capillary lengths calculated for three capillary diameters describing Schemes 1-3.
[0121] In one embodiment, the capillary length is between 0.1 m and 10 m in length. Capillaries with geometries in these ranges are compatible with the liquid handling technologies described in FIG. 9B to dispense ARM liquids from a filled capillary, and FIGS. 10A, 10B, 11A, and 11B to fill capillaries with ARM liquids.
[0122] In Table 2 all conditions except Scheme 3 with 41-100 pL volumes provide a capillary length above 0.1 m and below 10 m. For capillary ampules housing Scheme 3 conditions, volumes less than 100 pL may be indicated.
[0124] Experimental :
[0125] Preparation of deactivated coatings inside the capillary:
[0126] Preparation of the fluorinated silane reagent solution
[0127] Tris(pentafluorophenyl)borane (CAS #1109-15-5), >98% was purchased from TCI America and (tridecafluoro-l,l,2,2-tetrahydrooctyl)silane (CAS # 469904-32-3), 97%, was obtained from Gelest, Inc. (Morrisville, PA).
[0128] Tris(perfluorophenyl)borane (123 pmol, 63 mg) was dispersed in 20 mL anhydrous dichloromethane in a 60 mL reagent bottle. (Tri decafluoro- 1,1, 2, 2-tetrahydrooctyl)silane (6.14 mmol, 1.61 mL) was then added to the bottle. Reagents were used immediately after preparation and then discarded.
[0129] Capillary deactivation with fluorinated coating
[0130] 0.32 mm ID and 0.25 mm ID fused capillary was purchased from MicroQuartz
(Munich, Germany). Thirty-meter lengths were first pre-rinsed with 3 mL anhydrous di chloromethane.
[0131] Rinsed capillaries were introduced to the reagent bottle through an airtight connection in the cap. The inlets of the capillaries in the bottle were immersed into the silane/catalyst solution. A nitrogen line was also introduced to the bottle through an airtight connection in the cap, and a head pressure was adjusted to 138 kPa for reagent flow through the capillaries. On the opposite end of the capillaries, the silane solution was collected in an airtight bottle assembly and the nitrogen line was replaced with a vent line exhausting to a hood.
[0132] Reagent was flowed through the capillaries, from one bottle to the other under a nitrogen blanket. When the volume of the first bottle was fully transferred to the second bottle, the gas line and vent lines were reversed and the reagent flowed in the opposite direction back to the first bottle.
[0133] During flow, the reagent reacted with the inner surface of the capillary, yielding a monolayer coating of silane on the inside surface of the capillaries. Hydrogen was also generated, and the bubbles were monitored to ensure complete coverage of the surface. When no more bubbles were observed, the flow was stopped. The reaction was generally observed to be complete with less than three full cycles of the reagent.
[0134] Deactivated capillaries (labeled “Fused Silica + CF3”) were then rinsed with 3 mL anhydrous dichloromethane per capillary. Capillaries were then dried under nitrogen flow at 60 °C for two hours. Capillary ends were then flame sealed for storage.
[0135] Preparation of the DMDCS silane reagent solution
[0136] A 5% wt/wt solution of DMDCS (Dimethyldichlorosilane, CAS# 75-78-5) in toluene solution was prepared under a nitrogen blanket. DMDCS is highly reactive in water and care was taken to prevent reaction with atmospheric humidity.
[0137] Capillary deactivation with DMDCS coating
[0138] 0 ,32mm ID and 0.25mm ID fused capillary was purchased from MicroQuartz (Munich,
Germany). 30 m lengths were first pre-rinsed with 3 mL toluene. 20 mL of DMDCS solution was loaded into an airtight bottle. Rinsed capillaries were introduced to the reagent bottle through an airtight connection in the cap. The inlet of the capillaries in the bottle were immersed into the
DMDCS solution. A nitrogen line was also introduced to the bottle through an airtight connection in the cap, and a head pressure was adjusted to 138 kPa for reagent flow through the capillaries. On the opposite end of the capillaries, the DMDCS solution was collected in an airtight bottle assembly and the nitrogen line was replaced with a vent line exhausting to a hood.
[0139] Reagent was flowed through the capillaries, from one bottle to the other under a nitrogen blanket. When the volume of the first bottle was fully transferred to the second bottle, the gas line and vent lines were reversed and the reagent flowed in the opposite direction back to the first bottle. Three full rinse cycles of the DMDCS solution was flowed through the capillary.
[0140] Deactivated capillaries (labeled “Fused Silica + CF3”) were then rinsed with 3 mL anhydrous di chloromethane per capillary. Capillaries were then dried under nitrogen flow at 60 °C for two hours. Capillary ends were then flame sealed for storage.
[0141] PTFE tubing
[0142] Polytetrafluoroethylene (PTFE, TEFLON®) tubing was purchased from Scientific Commodities Inc. (0.25mm ID, cat# BB311-32).
[0143] Experiment I: measuring liquid volume retention in capillary tubing.
[0144] The degree of surface adsorption/absorption for a given solvent-capillary system is dependent on the solvent surface tension, solvent viscosity, capillary wall total surface area and smoothness, and the hydrophobic natures of the solvent and capillary wall. Preferably, the capillary ampule exhibits little to no liquid retention. This promotes a quantitative transfer of the ARM fluid from the ampule, where the delivered fluid maintains the indicated sample composition and concentrations.
[0145] To measure the degree of surface adsorption/absorption for a given solvent-capillary system, approximately 10-20 pL of solution was loaded into the proximal end of a 500 cm length of capillary. The length of the liquid plug within the capillary was measured.
[0146] Using a 25 pL air-filled gas tight syringe, the liquid plug was then pushed approximately 450 cm down the length of the capillary (the distal end), and the length of the plug was measured again. The difference in volumes (measured in units of length) corresponded to
liquid retained on the capillary wall as a result of the movement down the capillary.
[0147] Surface adsorption/absorption was measured for uncoated fused silica capillary, Fused Silica + CF3 capillary and PTFE tubing. Three solvents of increasing hydrophobicity were used: methanol, methylene chloride, and hexane. Methylene blue (blue) or iodine (red) color indicators were added to the solvents to aid in visualization.
[0149] It is preferable that the capillary deliver the same volume of liquid as was previously loaded. It is also preferable the component concentrations of the liquid are the same delivered as was loaded. For this it is beneficial that the capillary inner surface should be resistant to liquid volume retention, or selective retention of components within the liquid volume.
[0150] In the cases of methanol and methylene chloride solvents, both the Fused Silica + CF3 capillary and PTFE tubing exhibited very low surface retention of the liquid volume. In the case of hexane as the solvent only the Fused Silica + CF3 capillary exhibited low liquid retention. For all three solvent systems the bare fused silica exhibited considerable retention, with the entire volume of liquid lost to the capillary walls before reaching the distal end of the column.
[0151] Based on this data the Fused Silica + CF3 capillary system was employed for further experiments as the candidate surface for capillary ampules, and the fused silica capillary was employed as a control.
[0152] Experiment II: repeatability of capillary loading system (FIG. 10).
[0153] A capillary loading system as illustrated in FIG. 10 was employed to fill five capillary lengths with the same volume. All capillaries 202 were fused silica, 0.32 mm ID, and previously treated with the CF3 coating.
[0154] Nitrogen was employed as a capillary purge, and the gas volume “push” syringe 278 was charged with nitrogen 270. Two 250 pL gastight precision glass syringes were employed as the syringes 260.
[0155] A fused silica capillary, approximately 120 cm in length and treated with CF3 was employed as the injection loop 268. Sample fused silica capillaries 202, approximately 200 cm in length and treated with CF3 were employed as the liquid volume receptacle. Methanol was employed as the first liquid volume 228. A syringe 278 filled with methanol 266 loaded the injection loop 750.
[0156] Capillary 202 was first purged with nitrogen while the valve 264 was in the FIG. 10B configuration. Following the nitrogen purge, the valve 264 switched to the FIG. 10A configuration. A volume of methanol 266 was pushed from syringe 260 into the injection loop 268. This ensured a fixed, reproducible volume of methanol to the be transferred into capillary 202. Following the filling of injection loop 268, the valve 264 was switched back to the FIG. 10B configuration and the nitrogen 270 pushed the methanol volume from the loop 268 into capillary 202.
[0157] Xue Li Guan, Dorothy Pei Shan Chang, Zhen Xuan Mok, Bemett Lee, Assessing
variations in manual pipetting: An under -investigated requirement of good laboratory practice, Journal of Mass Spectrometry and Advances in the Clinical Lab, Volume 30, 2023, pp. 25-29 measures the variance and precision with manual pipetting. The variance and precision of the capillary ampule 200 was compared to the results in Xue et al.
[0158] A gravimetric approach to determining the precision of the capillary load involved measuring a fixed volume of liquid. The mass of capillary 202 was measured before and after loading, and the calculated mass difference is the methanol delivered. The coefficient of variation (%CV) was calculated using the Equation 1 :
Equation 1
%CV = (standard deviation (reading) * 100)/mean (reading)
[0160] For five replicate runs using the same injection loop 750, A 0.39% variance was measured. The results are less than half of the 0.816% minimum and one quarter of the 1.554% maximum inter-day, single operator pipetting variance measured in Xue et al. for quantitative transfer.
[0161] When using ARM standards from a conventional ampule described in FIGS. 1 A-C, at
least one pipette cycle is required to transfer an aliquot of liquid from the ampule. Tn many cases additional dilution and transfer of aliquots is necessary to reach the desired sample concentrations. When the ARM standard delivered from the capillary ampule is used directly in chemical analysis applications, the first pipette transfer is eliminated. In some cases where the concentration of the capillary ampule represents the final desired concentration, all manual pipetting of the ARM standard is eliminated. As such, the capillary ampule greatly improves testing accuracy and precision in chemical analysis applications compared to ARM standards prepared from conventional ampules.
[0162] Experiment III: retention of ARM compound concentration, loaded vs. dispensed.
[0163] 100 pL of an ARM sample was loaded into a capillary 202 in the same fashion as
Experiment II. The liquid volumes concentration were measured on a gas chromatograph (“GC”) with a flame ionization detector (“FID”), first before loading using the stock solution from the ampule. The liquid volume in capillary 202 was then dispensed into a vial and analyzed in the same fashion. The GC-FID signals were compared to determine if the concentration of the sample loaded into the capillary changed as a result of being loaded into the capillary.
[0164] Deactivation of the glass surface inhibits surface-enhanced reactions and adsorption, which reduces or prevents concentration changes of the compounds in solution. Three ARM standards used in this experiment were purchased from Restek Corp. (Bellefonte, PA):
1,4-Dioxane Standard, 2,000 pg/mL, P&T Methanol, 1 mL/ampul (Catalog No. 30287)
1,4-Dioxane Standard, 1.9 mg/mL, DMSO, 1 mL/ampul (Catalog No. 36294)
Vinyl Acetate Standard, 2000 pg/mL, P&T Methanol, 1 mL/ampul (Catalog No. 30216)
[0165] Volumes of these standards were individually used to compare the rates of compound loss in capillary ampules, compared to the commercially available ampules.
[0166] Capillary ampules 200 as described in FIG. 2A were constructed. 100 pL of standard solution was loaded into 2 m long bare fused silica capillaries, and silica + CF3 deactivated capillaries employing the loading fixture described in FIG. 10. Nitrogen gas was used as headspace volumes and the capillary ends were flame sealed. Three of both capillary types were immediately
opened and the contents were analyzed by GC-FTD.
[0167] Chromatograms generated by GC-FID analysis of the samples yielded peak area values for all compounds detected. Comparison of the vinyl acetate peak area measured for the commercial ampule (control) and the capillary ampule 200 showed the amount of vinyl acetate loss due to adsorption and degradation mechanisms.
[0168] Table 5. 1,4-Dioxane 1,000 ppm concentration comparison, dispensed vs. loaded; solvent = MeOH.
[0169] Table 6. 1,4-Dioxane 1,000 ppm concentration comparison, loaded vs. dispensed; solvent = DMSO.
[0170] Table 7. Vinyl acetate 1,000 ppm concentration comparison, loaded vs. dispensed; solvent = MeOH.
[0171] In Table 5, both bare silica and CF3 coated silica yielded concentration values greater than 99% of the values obtained by the ampule in methanol solvent.
[0172] In Table 6, bare silica capillary yielded concentration values greater than 99% of the compound concentration in DMSO solvent as measured for the ampule. The CF3 coated capillary yielded greater than 90% of the value.
[0173] In Table 7, the CF3 coated silica yielded concentration values greater than 96% of the values obtained by the ampule, while the bare silica indicated greater compound loss from capillary loading.
[0174] This data indicates these capillary surfaces may be used as suitable ampule containers, with exemplary performance achieved for individual compounds and solvents systems.
[0175] While the foregoing specification illustrates and describes exemplary embodiments, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from the essential scope thereof. Therefore, it is intended that the invention not be limited to the particular embodiment disclosed as the best mode contemplated for carrying out this invention, but that the invention will include all embodiments falling within the scope of the appended claims.
Claims
1. A capillary ampule, comprising: a capillary tube having: an outer diameter at an outer surface of the capillary tube; an inner diameter at an inner surface of the capillary tube; a wall thickness of a capillary wall between the outer diameter and the inner diameter; a first end; a second end; a length from the first end to the second end; and an internal volume formed by the inner diameter along the length; a first hermetic seal disposed at the first end of the capillary tube; a second hermetic seal disposed at the second end of the capillary tube; a first liquid volume disposed within the internal volume of the capillary tube; a first headspace volume disposed within the internal volume of the capillary tube between the first liquid volume and the first hermetic seal; and a second headspace volume disposed within the internal volume of the capillary tube between the first liquid volume and the second hermetic seal.
2. The capillary ampule of claim 1, wherein the first liquid volume includes an analytical reference material.
3. The capillary ampule of claim 1, further including: a second liquid volume disposed within the internal volume of the capillary tube disposed between the first liquid volume and the second hermetic seal; the second headspace volume being disposed within the internal volume of the capillary tube between the second liquid volume and the second hermetic seal; and a barrier volume disposed within the internal volume between the first liquid volume and the second liquid volume, wherein the barrier volume maintains a separation of the first liquid volume and the second liquid volume such that the first liquid volume is isolated from the second liquid
volume.
4. The capillary ampule of claim 3, wherein the first liquid volume includes a first analytical reference material and the second liquid volume includes a second analytical reference material, the first analytical reference material being compositionally distinct from the second analytical reference material.
5. The capillary ampule of claim 4, wherein first analytical reference material is chemically incompatible with the second analytical reference material.
6. The capillary ampule of claim 3, further including a third liquid volume disposed in the internal volume between the first liquid volume and the second liquid volume, the barrier volume including a first portion disposed between the first liquid volume and the third liquid volume and a second portion disposed between the third liquid volume and the second liquid volume, wherein the first portion of the barrier volume maintains a separation of the first liquid volume and the third liquid volume such that the first liquid volume is isolated from the third liquid volume and the second portion of the barrier volume maintains a separation of the second liquid volume and the third liquid volume such that the second liquid volume is isolated from the third liquid volume.
7. The capillary ampule of claim 3, further including a plurality of additional liquid volumes disposed in the internal volume between the first liquid volume and the second liquid volume, the barrier volume including a plurality of portions disposed between the first liquid volume, the second liquid volume and each of the plurality of additional liquid volumes, wherein the plurality of portions of the barrier volume maintains a separation of the first liquid volume, the second liquid volume and each of the plurality of additional liquid volumes volume such that the first liquid volume, the second liquid volume, and each of the plurality of additional liquid volumes are isolated from one another.
8. The capillary ampule of claim 3, wherein the first headspace volume, the second headspace volume, and the barrier volume are gaseous volumes.
9. The capillary ampule of claim 1, wherein the capillary tube is formed from a material selected from the group consisting of fused silica, borosilicate, polymer, metal, and combinations thereof.
10. The capillary ampule of claim 1, wherein: the first hermetic seal is a first end cap and the second hermetic seal is a second end cap; the first end cap sealingly mates with at least one of the outer surface of the capillary tube or the inner surface of the capillary tube; and the second end cap sealingly mates with at least one of the outer surface of the capillary tube or the inner surface of the capillary tube.
11. The capillary ampule of claim 10, wherein the first end cap sealingly mates with the outer surface of the capillary tube and the inner surface of the capillary tube and the second end cap sealingly mates with the outer surface of the capillary tube and the inner surface of the capillary tube.
12. The capillary ampule of claim 10, wherein at least one of the first end cap or the second end cap includes a depression configured to localize breakage of the capillary tube.
13. The capillary ampule of claim 1, wherein one of the first hermetic seal or the second hermetic seal is a first end cap and the other of the first hermetic seal or the second hermetic seal is flame-sealed.
14. The capillary ampule of claim 1, wherein the capillary tube includes at least one rinse liquid volume disposed within the internal volume of the capillary tube.
15. The capillary ampule of claim 1, further including a housing, the capillary tube being at least partially disposed within an interior cavity of the housing.
16. The capillary ampule of claim 15, wherein a portion of the capillary tube including the first end of the capillary tube extends out of the housing through a first aperture of the housing and a portion of the capillary tube including the second end of the capillary tube extends out of the housing through a second aperture of the housing.
17. The capillary ampule of claim 16, wherein each of the first aperture of the housing and the second aperture of the housing is a luer lock.
18. A capillary ampule system, comprising a plurality of capillary ampules according to claim 1.
19. The capillary ampule system of claim 18, wherein the plurality of capillary ampules are affixed to one another in a linear array.
20. The capillary ampule system of claim 18, wherein the plurality of capillary ampules are affixed to one another in an annular array.
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US10252938B2 (en) | 2011-07-04 | 2019-04-09 | Hitachi, Ltd. | Glass composition, glass frit containing same, glass paste containing same, and electrical/electronic component obtained using same |
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US10913680B2 (en) | 2016-01-18 | 2021-02-09 | Hitachi, Ltd. | Lead-free glass composition, glass composite material, glass paste, sealing structure, electrical/electronic component and coated component |
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US10252938B2 (en) | 2011-07-04 | 2019-04-09 | Hitachi, Ltd. | Glass composition, glass frit containing same, glass paste containing same, and electrical/electronic component obtained using same |
US20150284710A1 (en) * | 2012-11-12 | 2015-10-08 | Seiko Epson Corporation | Method of manipulating solid carriers and an apparatus of manipulating solid carriers |
US10913680B2 (en) | 2016-01-18 | 2021-02-09 | Hitachi, Ltd. | Lead-free glass composition, glass composite material, glass paste, sealing structure, electrical/electronic component and coated component |
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